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Penetrance, variable expressivity and monogenic neurodevelopmental disorders Eur. J. Med. Genet. (IF 1.9) Pub Date : 2024-03-05 Servane de Masfrand, Benjamin Cogné, Mathilde Nizon, Wallid Deb, Alice Goldenberg, François Lecoquierre, Gaël Nicolas, Marie Bournez, Antonio Vitobello, Frédéric Tran Mau-Them, Gwenaël le Guyader, Frédéric Bilan, Peter Bauer, Christiane Zweier, Juliette Piard, Laurent Pasquier, Stéphane Bézieau, Bénédicte Gerard, Laurence Faivre, Pascale Saugier-Veber, Amélie Piton, Bertrand Isidor
Incomplete penetrance is observed for most monogenic diseases. However, for neurodevelopmental disorders, the interpretation of single and multi-nucleotide variants (SNV/MNVs) is usually based on the paradigm of complete penetrance. From 2020 to 2022, we proposed a collaboration study with the French molecular diagnosis for intellectual disability network. The aim was to recruit families for whom the
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Clinical manifestations and genetic mutation analysis of patients with mucopolysaccharidosis type VII in China Eur. J. Med. Genet. (IF 1.9) Pub Date : 2024-03-03 Xueying Su, Xiaoyuan Zhao, Xi Yin, Li Liu, Yonglan Huang, Chunhua zeng, Xiuzhen Li, Wen Zhang
This study aimed to explore the clinical and genetic features of Chinese patients with mucopolysaccharidosis type VII (MPS VII), thereby improving early detection, disease management, and patient outcomes. A retrospective review of medical records for five patients presenting with coarse facial features, rib protrusion, chest deformities, and scoliosis was conducted. Exome sequencing was employed to
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A systematic review of the assessment of the clinical utility of genomic sequencing: Implications of the lack of standard definitions and measures of clinical utility Eur. J. Med. Genet. (IF 1.9) Pub Date : 2024-03-01 Claudia Azuelos, Marc-Antoine Marquis, Anne-Marie Laberge
Exome sequencing (ES) and genome sequencing (GS) are diagnostic tests for rare genetic diseases. Studies report clinical utility of ES/GS. The goal of this systematic review is to establish how clinical utility is defined and measured in studies evaluating the impacts of ES/GS results for pediatric patients. Relevant articles were identified in PubMed, Medline, Embase, and Web of Science. Eligible
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Disclosure of genetic risk to family members: A qualitative study on healthcare professionals' perceived roles and responsibilities Eur. J. Med. Genet. (IF 1.9) Pub Date : 2024-02-29 Álvaro Mendes, Milena Paneque, Jorge Sequeiros
This paper presents the perspectives of healthcare professionals regarding their roles and responsibilities in supporting patients with the disclosure of genetic risk to their families. The study involved eight focus groups and two individual interviews with 34 healthcare professionals working in medical genetics services across Portugal. The data were analyzed thematically, resulting in three primary
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Ligamentous laxity in children with achondroplasia: Prevalence, joint involvement, and implications for early intervention strategies Eur. J. Med. Genet. (IF 1.9) Pub Date : 2024-02-28 Domenico Marco Romeo, Virginia Pironi, Chiara Velli, Elisabetta Sforza, Donato Rigante, Valentina Giorgio, Chiara Leoni, Cristina De Rose, Eliza Maria Kuczynska, Domenico Limongelli, Roberta Ruiz, Cristiana Agazzi, Eugenio Mercuri, Giuseppe Zampino, Roberta Onesimo
Achondroplasia (ACH), the most common form of skeletal dysplasia, is characterized by severe disproportionate short stature, rhizomelia, exaggerated lumbar lordosis, brachydactyly, macrocephaly with frontal bossing and midface hypoplasia.
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Two siblings with PEX11B-related peroxisome biogenesis disorder Eur. J. Med. Genet. (IF 1.9) Pub Date : 2024-02-28 Somayeh Khoddam, Neda Kamal, Amirmasoud Shiri, Hossein Jafari Khamirani, Jamal Manoochehri, Mehdi Dianatpour, Seyed Mohammad Bagher Tabei, Seyed Alireza Dastgheib
The gene contains four exons and encodes peroxisomal membrane protein 11β, which is involved in peroxisome proliferation and division. Pathogenic variants in this gene result in a rare genetic disorder with autosomal recessive inheritance called peroxisome biogenesis disorder 14B (MIM: 614920). Here, we report two affected siblings with a novel variant (NM_003846: c.11G > A, p. Trp4Ter) in the gene
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Prenatal onset GAPO syndrome with a novel ANTXR1 variant in an Indian child: Expansion of the phenotype & literature review Eur. J. Med. Genet. (IF 1.9) Pub Date : 2024-02-28 Surya Balakrishnan, Iravathy Goud, Madhavi Latha Teegala
GAPO syndrome is a rare genetic condition caused by bi-allelic variants in gene & is an abbreviation for its core features - growth retardation, alopecia, pseudo-anodontia & optic atrophy. Certain additional features involving various other systems have been reported over the years & contribute to the expanding spectrum of this evolving phenotype. We report GAPO syndrome in a 3.75 year old Indian female
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Long-term clinical evaluation of patients with alpha-mannosidosis – A multicenter study Eur. J. Med. Genet. (IF 1.9) Pub Date : 2024-02-19 Engin Köse, Çiğdem Seher Kasapkara, Aslı İnci, Yılmaz Yıldız, İlknur Sürücü Kara, Ayça Burcu Kahraman, Leyla Tümer, Ali Dursun, Fatma Tuba Eminoğlu
Alpha mannosidosis is an autosomal recessive lysosomal storage disorder caused by biallelic pathogenic variants in the gene. It manifests with clinical features, including intellectual disability, hearing impairment, coarse facial appearance, skeletal anomalies, immunodeficiency, central nervous system involvement, psychiatric comorbidities, corneal opacity, and hepatosplenomegaly. Sixteen patients
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Imaging in osteogenesis imperfecta: Where we are and where we are going Eur. J. Med. Genet. (IF 1.9) Pub Date : 2024-02-16 S. Gazzotti, R. Sassi, M.P. Aparisi Gómez, A. Moroni, E. Brizola, M. Miceli, A. Bazzocchi
Osteogenesis imperfecta (OI) is a rare phenotypically and genetically heterogeneous group of inherited skeletal dysplasias. The hallmark features of OI include bone fragility and susceptibility to fractures, bone deformity, and diminished growth, along with a plethora of associated secondary features (both skeletal and extraskeletal). The diagnosis of OI is currently made on clinical grounds and may
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Genome sequencing identify chromosome 9 inversions disrupting ENG in 2 unrelated HHT families Eur. J. Med. Genet. (IF 1.9) Pub Date : 2024-02-12 M. Tusseau, M. Eyries, N. Chatron, F. Coulet, A. Guichet, E. Colin, B. Demeer, H. Maillard, J. Thevenon, C. Lavigne, V. Saillour, C. Paris, J.M. De Sainte Agathe, M. Pujalte, A. Guilhem, S. Dupuis-Girod, G. Lesca
Hereditary hemorrhagic telangiectasia (HHT), also known as Rendu-Osler-Weber disease, is a dominant inherited vascular disorder. The clinical diagnosis is based on the Curaçao criteria and pathogenic variants in the and genes are responsible for most cases of HHT.
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A rare skeletal dysplasia in the etiology of severe scoliosis: Diaphanospondylodysostosis Eur. J. Med. Genet. (IF 1.9) Pub Date : 2024-02-12 Tuğba Daşar, Adalet Elçin Yıldız, Gökhan Demirkıran, Gülen Eda Utine, Pelin Özlem Şimşek Kiper
Diaphanospondylodysostosis is a rare genetic skeletal disorder caused by biallelic variants in the gene. The term, diaphanospondylodysostosis, includes ischiospinal dysotosis, which was previously known as a distinct entity with milder clinical features. The clinical phenotype of diaphanospondylodysostosis is quite variable with mortality in early postnatal life in some patients. Main clinical and
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Beyond 'speech delay': Expanding the phenotype of BRPF1-related disorder Eur. J. Med. Genet. (IF 1.9) Pub Date : 2024-02-10 Lottie D. Morison, Olivia Van Reyk, Emma Baker, Lyse Ruaud, Nathalie Couque, Alain Verloes, David J. Amor, Angela T. Morgan
Pathogenic variants in cause intellectual disability, ptosis and facial dysmorphism. Speech and language deficits have been identified as a manifestation of related disorder but have not been systematically characterized. We provide a comprehensive delineation of speech and language abilities in -related disorder and expand the phenotype. Speech and language, and health and medical history were assessed
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TBX5 variants and cardiac phenotype: A systematic review of the literature and a novel variant Eur. J. Med. Genet. (IF 1.9) Pub Date : 2024-02-07 Anne Kathrine Møller Nielsen, Anna Maria Dehn, Vibeke Hjortdal, Lars Allan Larsen
T-Box Transcription Factor 5 () variants are associated with Holt-Oram syndrome. Holt-Oram syndrome display phenotypic variability, regarding upper limb defects, congenital heart defects, and arrhythmias. To investigate the genotype-phenotype relationship between variants and cardiac disease, we performed a systematic review of the literature. Through the systematic review we identified 108 variants
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Impressive clinical improvement and disappearance of neuropathic pain in an adult patient with hypophosphatasia treated with asfotase alfa Eur. J. Med. Genet. (IF 1.9) Pub Date : 2024-02-05 Zografia Zervou, Roel Plooij, Evert F.S. van Velsen, Remco G.M. Timmermans, Serwet Demirdas, M. Carola Zillikens
Hypophosphatasia (HPP) is a rare disorder, resulting from loss-of-function variants of the ALPL gene encoding non-tissue specific alkaline phosphatase (TNSALP). Presentation varies largely, with increased severity usually occurring with earlier disease onset. Here we describe the clinical improvement of a 57-year-old woman with childhood onset HPP, after initiating treatment with asfotase alfa (Strensiq®)
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Development of a low-cost and accurate carrier screening method for spinal muscular atrophy in developing countries Eur. J. Med. Genet. (IF 1.9) Pub Date : 2024-02-05 Yu Jiang, Zhenyu Luo, Wenrong Wang, Xingxiu Lu, ZhongMin Xia, Jieqiong Xie, Mei Lu, Lili Wu, Yulin Zhou, Qiwei Guo
Heterozygous carriers of the survival of motor neuron 1 () gene deletion in parents account for approximately 95% of neonatal spinal muscular atrophy cases. Given the severity of the disease, professional organizations have recommended periconceptional spinal muscular atrophy carrier screening to all couples, regardless of race or ethnicity. However, the prevalence of screening activities in mainland
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Rapid exome sequencing for children with severe acute encephalopathy – A case series Eur. J. Med. Genet. (IF 1.9) Pub Date : 2024-02-05 Clair Habib, Tamar Paperna, Rinat Zaid, Sarit Ravid, Josef Ben Ari, Galit Tal, Karin Weiss, Tova Hershkovitz
Increasingly, next-generation sequencing (NGS) is becoming an invaluable tool in the diagnosis of unexplained acute neurological disorders, such as acute encephalopathy/encephalitis. Here, we describe a brief series of pediatric patients who presented at the pediatric intensive care unit with severe acute encephalopathy, initially suspected as infectious or inflammatory but subsequently diagnosed with
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Altered peripheral blood leukocyte subpopulations, function, and gene expression in children with Down syndrome: implications for respiratory tract infection Eur. J. Med. Genet. (IF 1.9) Pub Date : 2024-02-05 Kelley L. Colvin, Kristine Wolter-Warmerdam, Francis Hickey, Michael E. Yeager
We tested the hypothesis that aberrant expression of Hsa21-encoded interferon genes in peripheral blood immune cells would correlate to immune cell dysfunction in children with Down syndrome (DS). We performed flow cytometry to quantify peripheral blood leukocyte subtypes and measured their ability to migrate and phagocytose. In matched samples, we measured gene expression levels for constituents of
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X-linked hypophosphatemia: The value of feedback focus groups to assess patient and caregiver needs Eur. J. Med. Genet. (IF 1.9) Pub Date : 2024-02-01 Estelle Wagner, Aurélia Bertholet-Thomas, Mélanie Romier, Laure Loin, Sandrine Lemoine, Emmanuelle Vignot, Sacha Flammier, Charlotte Garnier, Aurélie De-Mul, Corinne Feutrier, Sandrine Juillard, Béatrice Thivichon-Prince, Guillemette Lienhart, Justine Bacchetta
X-linked hypophosphatemia (XLH) is a rare, multi-systemic, invalidating disease requiring a multi-disciplinary approach. No specific action in XLH, neither for the patients’ specific needs nor for the methodology for the evaluation of these were found. Thus, to identify the needs of XLH patients and their caregivers, we organised focus groups in our reference centre with a view to build educational
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ERN BOND: The key European network leveraging diagnosis, research, and treatment for rare bone conditions Eur. J. Med. Genet. (IF 1.9) Pub Date : 2024-02-01 Lorena Casareto, Natasha M. Appelman-Dijkstra, Maria Luisa Brandi, Roland Chapurlat, Valérie Cormier-Daire, Neveen A.T. Hamdy, Karen E. Heath, Joachim Horn, Giovanna Mantovani, Klaus Mohnike, Sérgio Bernardo Sousa, André Travessa, Lena Lande Wekre, M. Carola Zillikens, Luca Sangiorgi, the European Reference Network on rare BONe Diseases
There is no universally accepted definition for rare diseases: in Europe a disease is considered to be rare when affecting fewer than 1 in 2000 people. European Reference Networks (ERNs) have been the concrete response to address the unmet needs of rare disease patients and many pan-European issues in the field, reducing inequities, and significantly increasing accessibility to high-quality healthcare
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Recurrent MECR R258W causes adult-onset optic atrophy: A case report Eur. J. Med. Genet. (IF 1.9) Pub Date : 2024-02-01 Nan Jia, Shuiqing Yu, Geng Zhang, Lin Li, Jiawei Wang, Chuntao Lai
-related neurologic disorder, also known as mitochondrial enoyl CoA reductase protein-associated neurodegeneration (MEPAN) or dystonia with optic atrophy and basal ganglia abnormalities in childhood (MIM: #), is an autosomal recessive inherited disease characterized by a progressive childhood-onset movement disorder and optic atrophy. Here we report a 19-year-old male, presented with progressive visual
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Pachydysostosis of the fibula in a case of familial adenomatous polyposis Eur. J. Med. Genet. (IF 1.9) Pub Date : 2024-01-28 Daniela Oliveira, Sofia Maia, Inês Balacó, Paulo Coelho, Susana Almeida, Margarida Venâncio, Jorge Saraiva, Gen Nishimura, Sérgio B. Sousa
Familial Adenomatous Polyposis (FAP) is a colorectal cancer (CRC) predisposition syndrome caused by germline mutations and characterised by an increased risk of CRC and colonic polyps and, in certain forms, of specific prominent extraintestinal manifestations, namely osteomas, soft tissue tumours and dental anomalies. Pachydysostosis of the fibula is a rare clinical entity defined by unilateral bowing
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A spectrum of TP63-related disorders with eight affected individuals in five unrelated families Eur. J. Med. Genet. (IF 1.9) Pub Date : 2024-01-26 Merve Soğukpınar, Gülen Eda Utine, Koray Boduroğlu, Pelin Özlem Şimşek-Kiper
-related disdorders broadly involve varying combinations of ectodermal dysplasia (sparse hair, hypohydrosis, tooth abnormalities, nail dysplasia), cleft lip/palate, acromelic malformation, split-hand/foot malformation/syndactyly, ankyloblepharon filiforme adnatum, lacrimal duct obstruction, hypopigmentation, and hypoplastic breasts and/or nipples. -related disorders are associated with heterozygous
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Lenz-Majewski syndrome and recurrent otitis media: Are they related or not? Eur. J. Med. Genet. (IF 1.9) Pub Date : 2024-01-21 Fayize Maden Bedel, Özgür Balasar, Selma Erol Aytekin, Sevgi Keleş, Hüseyin Çaksen
Lenz-Majewski hyperostotic dwarfism (LMHD) is a rare condition characterized by intellectual disability, sclerosing bone dysplasia, dysmorphic facial features, brachydactyly, symphalangism and cutis laxa. Nineteen cases have been reported in the literature so far, eleven of them with PTDSS1 mutations. Although studies have had clinically similar findings, in some cases the authors have reported even
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Evaluating ClinGen variant curation expert panels' application of PVS1 code Eur. J. Med. Genet. (IF 1.9) Pub Date : 2024-01-08 Xiaoyan Wang, Haibo Li, Haiyan Luo, Yongyi Zou, Haoxian Li, Yayun Qin, Jieping Song
Background The 2015 American College of Medical Genetics and Genomics (ACMG) and Association for Molecular Pathology (AMP) guidelines articulates that the effects of certain types of variants on gene function can often be seen as a complete absence of the gene product by leading to a lack of transcription or nonsense-mediated decay(NMD). However, detailed information considering different types of
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Genetic counselling supervision: Luxury or necessity? A qualitative study with genetic healthcare professionals in Portugal Eur. J. Med. Genet. (IF 1.9) Pub Date : 2023-12-22 Lídia Guimarães, Ruxanda Baião, Catarina Costa, Marina Lemos, Margarida Rangel Henriques, Milena Paneque
In recent years, there has been a significant technological evolution in the field of genetics, leading to an increase in the number of professionals working in medical genetics and, consequently, a tremendous growth in genetic counselling. At the same time, there has been a growing recognition of the parameters on which to base a safe practice, not only regarding the technical skills of the professional
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Fetal hepatic calcification in severe KAT6A (Arboleda-Tham) syndrome Eur. J. Med. Genet. (IF 1.9) Pub Date : 2023-12-22 Antonella Di Caprio, Cecilia Rossi, Emma Bertucci, Luca Bedetti, Natascia Bertoncelli, Francesca Miselli, Lucia Corso, Carolina Bondi, Lorenzo Iughetti, Alberto Berardi, Licia Lugli
Arboleda-Tham syndrome (ARTHS, MIM 616268) is a rare genetic disease, due to a pathogenic variant of Lysine (K) Acetyltransferase 6A (KAT6A) with autosomal dominant inheritance. Firstly described in 2015, ARTHS is one of the more common causes of undiagnosed syndromic intellectual disability. Due to extreme phenotypic variability, ARTHS clinical diagnosis is challenging, mostly at early stage of the
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Deep intronic variant causes aberrant splicing of ATP7A in a family with a variable occipital horn syndrome phenotype Eur. J. Med. Genet. (IF 1.9) Pub Date : 2023-12-21 J. Robert Harkness, Huw B. Thomas, Jill E. Urquhart, Peter Jamieson, , Raymond T. O'Keefe, Helen M. Kingston, Charulata Deshpande, William G. Newman
Genetic variants in ATP7A are associated with a spectrum of X-linked disorders. In descending order of severity, these are Menkes disease, occipital horn syndrome, and X-linked distal spinal muscular atrophy. After 30 years of diagnostic investigation, we identified a deep intronic ATP7A variant in four males from a family affected to variable degrees by a predominantly skeletal phenotype, featuring
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The VASCERN PPL working group patient pathway for primary and paediatric lymphoedema Eur. J. Med. Genet. (IF 1.9) Pub Date : 2023-12-23 Nele Devoogdt, Sarah Thomis, Florence Belva, Janine Dickinson-Blok, Caroline Fourgeaud, Guido Giacalone, Tonny Karlsmark, Heli Kavola, Vaughan Keeley, Manuela Lourenço Marques, Sahar Mansour, Christoffer V. Nissen, Susan Nørregaard, Michael Oberlin, Tanja Planinšek Ručigaj, Gloria Somalo-Barranco, Sinikka Suominen, Kirsten Van Duinen, Stéphane Vignes, Robert Damstra
Lymphoedema is caused by an imbalance between fluid production and transport by the lymphatic system. This imbalance can be either caused by reduced transport capacity of the lymphatic system or too much fluid production and leads to swelling associated with tissue changes (skin thickening, fat deposition). Its main common complication is the increased risk of developing cellulitis/erysipelas in the
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Pathological mandibular fracture complicated by osteonecrosis in an adult patient with pycnodysostosis: clinical report and review of the literature Eur. J. Med. Genet. (IF 1.9) Pub Date : 2023-12-22 Alice Moroni, Evelise Brizola, Alessia Di Cecco, Morena Tremosini, Marta Sergiampietri, Alberto Bianchi, Barbara Tappino, Maria Piana, Maria Gnoli
Pycnodysostosis is an ultra-rare osteosclerotic skeletal disorder characterized by short stature, susceptibly to fractures, acroosteolysis of the distal phalanges, and craniofacial features (frontal bossing, prominent nose, obtuse mandibular angle, micrognathia). Dental abnormalities (delayed eruption of teeth, hypodontia, malocclusion, dental crowding, persistence of deciduous teeth, enamel hypoplasia
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Associated anomalies in anophthalmia and microphthalmia Eur. J. Med. Genet. (IF 1.9) Pub Date : 2023-12-16 Claude Stoll, Beatrice Dott, Yves Alembik, Marie-Paule Roth
Infants with anophthalmia and microphthalmia (an/microphthalmia) have often other associated congenital anomalies. The reported frequency and the types of these associated anomalies vary between different studies. The purpose of this investigation was to assess the frequency and the types of associated anomalies among cases with an/microphthalmia in a geographically well defined population of northeastern
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LRP4 site-specific variants in the third β-propeller domain causes congenital myasthenic syndrome type 17 Eur. J. Med. Genet. (IF 1.9) Pub Date : 2023-12-13 Tariq Al Jabry, Nadia Al-Hashmi, Basem Abdelhadi, Almundher Al-Maawali
LRP4 is expressed in many organs. It mediates SOST-dependent inhibition of bone formation and acts as an inhibitor of WNT signaling. It is also a postsynaptic end plate cell surface receptor at the neuromuscular junction and is central to its development, maintenance, and function. Pathogenic variants of LRP4 that specifically affect the canonical WNT signaling pathway are known to be associated with
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Progressive myoclonic epilepsy as an expanding phenotype of NGLY1-associated congenital deglycosylation disorder: A case report and review of the literature Eur. J. Med. Genet. (IF 1.9) Pub Date : 2023-12-07 Yuri Sonoda, Atsushi Fujita, Michiko Torio, Takahiko Mukaino, Ayumi Sakata, Masaru Matsukura, Kousuke Yonemoto, Ken Hatae, Yuko Ichimiya, Pin Fee Chong, Masayuki Ochiai, Yoshinao Wada, Machiko Kadoya, Nobuhiko Okamoto, Yoshiko Murakami, Tadashi Suzuki, Noriko Isobe, Hiroshi Shigeto, Naomichi Matsumoto, Yasunari Sakai, Shouichi Ohga
Introduction NGLY1-associated congenital disorder of deglycosylation (CDDG1: OMIM #615273) is a rare autosomal recessive disorder caused by a functional impairment of endoplasmic reticulum in degradation of glycoproteins. Neurocognitive dysfunctions have been documented in patients with CDDG1; however, deteriorating phenotypes of affected individuals remain elusive. Case presentation A Japanese boy
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GRM7-related disorder: five additional patients from three independent families and review of the literature Eur. J. Med. Genet. (IF 1.9) Pub Date : 2023-12-08 Louis Januel, Nicolas Chatron, Clotilde Rivier-Ringenbach, Sara Cabet, Audrey Labalme, Yavuz Sahin, Hossein Darvish, Michael Kruer, Somayeh Bakhtiari, Damien Sanlaville, Jean Madeleine de Sainte Agathe, Gaetan Lesca
Developmental and epileptic encephalopathies (DEEs) refer to a group of severe epileptic syndromes characterized by seizures as well as a developmental delay which can be a consequence of the underlying etiology and/or the epileptic encephalopathy. The genes responsible for DEEs are numerous and their number is increasing since the availability of Next-Generation Sequencing. Pathogenic variants in
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Combined achondroplasia and short stature homeobox-containing (SHOX) gene deletion in a Danish infant Eur. J. Med. Genet. (IF 1.9) Pub Date : 2023-12-07 Kasper V. Seiersen, Tine B. Henriksen, Ted C.K. Andelius, Lotte Andreasen, Tue Diemer, Gudrun Gudmundsdottir, Ida Vogel, Vibike Gjørup, Pernille A. Gregersen
Short stature or shortening of the limbs can be the result of a variety of genetic variants. Achondroplasia is the most common cause of disproportionate short stature and is caused by pathogenic variants in the fibroblast growth factor receptor 3 gene (FGFR3). Short stature homeobox (SHOX) deficiency is caused by loss or defects of the SHOX gene or its enhancer region. It is associated with a spectrum
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Defining priorities in the transition from paediatric to adult healthcare for rare bone disease patients: a dialogic approach Eur. J. Med. Genet. (IF 1.9) Pub Date : 2023-11-30 D. Scognamiglio, M. Boarini, M.C. la Forgia, E. Grippa, S. Forni, A. Sergi, A. Romeo, G. Massa, L. Sangiorgi
The Italian patient association for Multiple Osteochondromas, Ollier Disease, and Maffucci Syndrome, Associazione Conto Alla Rovescia-ACAR Aps, conducted a mixed-methods study at its 2023 annual conference. The study included the Open Dialogue Approach and a feedback survey to identify the main priorities in the transitioning process from paediatric to adult healthcare for patients with Multiple Osteochondromas
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Secondary physical features in children with FASD Eur. J. Med. Genet. (IF 1.9) Pub Date : 2023-11-30 Miguel del Campo, Julie A. Kable, Claire D. Coles, Michael Suttie, Christina D. Chambers, Gretchen Bandoli
Objective The diagnoses included within the umbrella term fetal alcohol spectrum disorders (FASD), are based on the documentation of prenatal alcohol exposure (PAE), growth deficits and a pattern of dysmorphic physical features and neurobehavioral impairments. Although 3 key facial features (short palpebral fissures, a smooth philtrum and a thin vermilion of the upper lip) are the only dysmorphic features
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New description of an MRPS2 homozygous patient: Further features to help expend the phenotype Eur. J. Med. Genet. (IF 1.9) Pub Date : 2023-11-27 Thalia Papadopoulos, Pauline Gaignard, Manuel Schiff, Marlène Rio, Daniela Karall, Adrien Legendre, Alain Verloes, Lyse Ruaud
Mutated mito-ribosomal protein S2 (MRPS2) was already described in only three subjects, two with sensorineural hearing impairment, mild developmental delay, hypoglycemia, lactic acidemia and combined oxidative phosphorylation system deficiency and another, recently, presenting with a less severe phenotype. In order to expand the phenotype, we describe a new MRPS2 homozygous subject who shows particular
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Early-onset diabetes in Africa: A mini-review of the current genetic profile Eur. J. Med. Genet. (IF 1.9) Pub Date : 2023-11-21 Samuel Mawuli Adadey, Joy Afua Mensah, Kojo Sekyi Acquah, Abugri James, Richard Osei-Yeboah
Early-onset diabetes is poorly diagnosed partly due to its heterogeneity and variable presentations. Although several genes have been associated with the disease, these genes are not well studied in Africa. We sought to identify the major neonatal, early childhood, juvenile, or early-onset diabetes genes in Africa; and evaluate the available molecular methods used for investigating these gene variants
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Resolving fetal hydrops – A rare entity Eur. J. Med. Genet. (IF 1.9) Pub Date : 2023-11-20 Deepti Saxena, Amit K. Tiwari, Rameshwar Prasad, Saumya Srivastav
Non immune hydrops fetalis (NIHF) is abnormal accumulation of serous fluid in ≥2 interstitial spaces with no evidence of maternal red cell alloimmunization. Leaving a few treatable conditions, it is generally considered as a sign of poor fetal outcome. Bi-allelic variants in THSD1 have been found to be to be associated with phenotypes ranging from lethal NIHF to persistent edema. Here, we report a
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Clinical and molecular features of four families with CLDN10 associated HELIX syndrome Eur. J. Med. Genet. (IF 1.9) Pub Date : 2023-11-18 Ahmad Qudair, Maged Hussein, Mohammed Alowain, Zuhair Nasser Al-Hassnan, Abdullah Alfaifi, Abdullah Alfalah, Mashael Al-Qahtani, Fowzan S. Alkuraya
Biallelic pathogenic variants in CLDN10 cause the very rare and distinct multiplex epithelium dysfunction manifested by hypohidrosis and electrolyte imbalance (HELIX) syndrome. HELIX patients often present with heat intolerance and reduced tear secretion. Here, we report on eight new patients (four families) who presented soon after birth with fine scales in the palms and soles and hypohidrosis that
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Cardiovascular involvement in later-onset malonyl-CoA decarboxylase deficiency: Case studies and literature review Eur. J. Med. Genet. (IF 1.9) Pub Date : 2023-11-17 Emanuele Monda, Athanasios Bakalakos, Petros Syrris, Saidi Mohiddin, Sacha Ferdinandusse, Elaine Murphy, Perry Mark Elliott
Background Malonyl-CoA decarboxylase deficiency (MLYCDD) is an ultra-rare inherited metabolic disorder, characterized by multi-organ involvement manifesting during the first few months of life. Our aim was to describe the clinical, biochemical, and genetic characteristics of patients with later-onset malonyl-CoA decarboxylase deficiency. Methods Clinical and biochemical characteristics of two patients
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Response to the comment on Diderich et al. “The role of a multidisciplinary team in managing variants of uncertain clinical significance in prenatal genetic diagnosis” (EJMG 66(10),104844) Eur. J. Med. Genet. (IF 1.9) Pub Date : 2023-11-14 Karin E.M. Diderich, Jasmijn E. Klapwijk, Vyne van der Schoot, Myrthe van den Born, Martina Wilke, Marieke Joosten, Kyra E. Stuurman, Lies H. Hoefsloot, Diane Van Opstal, Hennie T. Brüggenwirth, Malgorzata I. Srebniak
Abstract not available
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National clinical Genetic Networks - GENets - Establishment of expert collaborations in Denmark Eur. J. Med. Genet. (IF 1.9) Pub Date : 2023-11-13 Dorte L. Lildballe, Anja Lisbeth Frederiksen, Bitten Schönewolf-Greulich, Charlotte Brasch-Andersen, Charlotte Kvist Lautrup, Helena Gásdal Karstensen, Inge Søkilde Pedersen, Lone Sunde, Lotte Risom, Maria Rasmussen, Mette Bertelsen, Mette Klarskov Andersen, Nanna Dahl Rendtorff, Pernille Axél Gregersen, Pernille M. Tørring, Sophia Hammer-Hansen, Susanne E. Boonen, Suzanne Granhøj Lindquist, Trine
Genetic conditions are often familial, but not all relatives receive counseling from the same institution. It is therefore necessary to ensure consistency in variant interpretation, counseling practices, and clinical follow up across health care providers. Furthermore, as new possibilities for gene-specific treatments emerge and whole genome sequencing becomes more widely available, efficient data
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Letter to the Editor: Comment to Diderich et al. “The role of a multidisciplinary team in managing variants of uncertain clinical significance in prenatal genetic diagnosis” (EJMG 66(10),104844) Eur. J. Med. Genet. (IF 1.9) Pub Date : 2023-11-08 Fang Chen, Dong-Zhi Li
Abstract not available
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Pathogenicity evaluation of variants of uncertain significance at exon-intron junction by splicing assay in patients with Mowat–Wilson syndrome Eur. J. Med. Genet. (IF 1.9) Pub Date : 2023-11-07 Yasuyo Suzuki, Noriko Nomura, Kenichiro Yamada, Yasukazu Yamada, Ayumi Fukuda, Kyoko Hoshino, Shinpei Abe, Kenji Kurosawa, Mie Inaba, Seiji Mizuno, Nobuaki Wakamatsu, Shin Hayashi
High-throughput sequencing has identified vast numbers of variants in genetic disorders. However, the significance of variants at the exon-intron junction remains controversial. Even though most cases of Mowat–Wilson syndrome (MOWS) are caused by heterozygous loss-of-function variants in ZEB2, the pathogenicity of variants at exon-intron junction is often indeterminable. We identified four intronic
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Data collection on rare bone and mineral conditions in Europe: The landscape of registries and databases Eur. J. Med. Genet. (IF 1.9) Pub Date : 2023-10-30 Ana Luisa Priego Zurita, Corinna Grasemann, Manila Boarini, Roland Chapurlat, Marina Mordenti, , Muhammad Kassim Javaid, Natasha M. Appelman-Dijkstra
Background knowledge on the natural history of rare diseases is necessary to improve outcomes. Disease registries may play a key role in covering these unmet needs in the rare bone and mineral community. Objective to map existing bone and mineral conditions registries in Europe and their characteristics. Methods online survey about the use of registries/databases and their characteristics. This survey
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Application of long read sequencing in rare diseases: The longer, the better? Eur. J. Med. Genet. (IF 1.9) Pub Date : 2023-10-29 Si-Yan Yu, Yu-Lin Xi, Fu-Qiang Xu, Jian Zhang, Yan-Shan Liu
Rare diseases encompass a diverse group of genetic disorders that affect a small proportion of the population. Identifying the underlying genetic causes of these conditions presents significant challenges due to their genetic heterogeneity and complexity. Conventional short-read sequencing (SRS) techniques have been widely used in diagnosing and investigating of rare diseases, with limitations due
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Therapeutic targeting in pediatric acute myeloid leukemia with aberrant HOX/MEIS1 expression Eur. J. Med. Genet. (IF 1.9) Pub Date : 2023-10-29 Kristian L. Juul-Dam, Neerav N. Shukla, Todd M. Cooper, Branko Cuglievan, Olaf Heidenreich, E Anders Kolb, Milad Rasouli, Henrik Hasle, C Michel Zwaan
Despite advances in the clinical management of childhood acute myeloid leukemia (AML) during the last decades, outcome remains fatal in approximately one third of patients. Primary chemoresistance, relapse and acute and long-term toxicities to conventional myelosuppressive therapies still constitute significant challenges and emphasize the unmet need for effective targeted therapies. Years of scientific
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Novel TRPS1 frameshift variant in tricho-rhino-phalangeal syndrome type I accompanied by zinc deficiency Eur. J. Med. Genet. (IF 1.9) Pub Date : 2023-10-23 Hideaki Yagasaki, Hiromune Narusawa, Daisuke Watanabe, Koji Kobayashi, Hiroshi Mitsui, Yoshihiro Asano, Miho Nagata, Ayumi Yonei, Takeshi Inukai
Tricho-rhino-phalangeal syndrome type I (TRPS1), caused by pathogenic variants in the transcriptional repressor GATA-binding 1 gene (TRPS1), is characterized by ectodermal and skeletal anomalies including short stature and sparse scalp hair during infancy. TRPS1 encodes a zinc finger protein transcription factor that contributes to bone homeostasis by regulating perichondral mineralization, chondrocyte
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Characterization of three adults and an adolescent with Osteogenesis Imperfecta type VI and a novel founder SERPINF1 variant Eur. J. Med. Genet. (IF 1.9) Pub Date : 2023-10-13 André M. Travessa, Patrícia Dias, Joana Rosmaninho-Salgado, Miriam Aza-Carmona, Oana Moldovan, Francisca Díaz‐González, Fátima Godinho, José Carlos Romeu, Filipa Oliveira-Ramos, Maria do Céu Barreiros, Sérgio B. Sousa, Karen E. Heath, Ana Berta Sousa
Osteogenesis imperfecta (OI) type VI is an extremely rare form of OI caused by biallelic variants in the SERPINF1 gene, which codes for the pigment-epithelium derived factor (PEDF). We report on four patients (three adults and one adolescent) with a severe deforming form of OI. All patients presented no abnormalities at birth, frequent long bone and vertebrae fractures (mainly during childhood), marked
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Serum alkaline phosphatase can be elevated in patients with hypophosphatasia due to liver disease Eur. J. Med. Genet. (IF 1.9) Pub Date : 2023-10-13 Evert F.S. van Velsen, Zografia Zervou, M. Carola Zillikens
Background Hypophosphatasia (HPP) is a rare inherited disorder caused by pathogenic loss-of-function variants in the ALPL gene, encoding the tissue-nonspecific isoenzym of alkaline phosphatase (ALP; TNSALP). Low serum ALP is the biochemical hallmark of HPP, but it is unknown whether ALP levels can increase due to concurring liver disease, which may lead to a missed diagnose of HPP. We present a patient
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Investigation of (Epi)genetic causes in syndromic short children born small for gestational age Eur. J. Med. Genet. (IF 1.9) Pub Date : 2023-09-25 Beyhan Tüysüz, Büşra Kasap, Dilek Uludağ Alkaya, Zeynep Alp Ünkar, Pınar Köseoğlu, Filiz Geyik, Emre Özer, Hasan Önal, Alper Gezdirici, Oya Ercan
Intrauterine onset syndromic short stature constitutes a group of diseases that pose challenges in differential diagnosis due to their rarity and clinical as well as molecular heterogeneity. The aim of this study was to investigate the presence of (epi)genetic causes in children born small for gestational age (SGA) and manifesting clinically undiagnosed syndromic short stature. The study group comprised
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Reassessment of the NF1 variants of unknown significance found during the 20-year activity of a genetics diagnostic laboratory Eur. J. Med. Genet. (IF 1.9) Pub Date : 2023-09-24 Davide Martorana, Valeria Barili, Vera Uliana, Enrico Ambrosini, Matteo Riva, Erika De Sensi, Elena Luppi, Corinne Messina, Edoardo Caleffi, Francesco Pisani, Antonio Percesepe
The finding of variants of uncertain significance (VUS) in the activity of a diagnostic genetic laboratory is a common issue, which is however provisional and needs to be periodically re-evaluated, due to the continuous advancements in our knowledge of the genetic diseases. Neurofibromatosis type 1, caused by the occurrence of heterozygous pathogenic NF1 variants, is a good model for studying the evolution
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PHGDH-related microcephalic dwarfism in two fetuses: Expanding the phenotypical spectrum of L-serine biosynthesis defect Eur. J. Med. Genet. (IF 1.9) Pub Date : 2023-09-25 Silvestre Cuinat, Chloé Quélin, Laurent Pasquier, Philippe Loget, Dominique Aussel, Sylvie Odent, Annie Laquerrière, Maia Proisy, Sylvie Mazoyer, Marion Delous, Patrick Edery, Nicolas Chatron, Gaetan Lesca, Audrey Putoux
Defects in L-serine biosynthesis are a group of autosomal recessive diseases resulting in a wide phenotypic spectrum ranging from viable to lethal presentations and caused by variants in the three genes encoding the L-serine biosynthesis enzymes, PHGDH, PSAT1, and PSPH. Neu-Laxova syndrome (NLS) is the fetal form of this group, characterized by multiple congenital anomalies including severe intrauterine
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Novel pathogenic variants in SPARC as cause of osteogenesis imperfecta: Two case reports Eur. J. Med. Genet. (IF 1.9) Pub Date : 2023-09-26 Silvia Storoni, Luca Celli, Lidiia Zhytnik, Katre Maasalu, Aare Märtson, Sulev Kõks, Sergey Khmyzov, Andrei Pashenko, Alessandra Maugeri, Anna Zambrano, Mauro Celli, Elisabeth M.W. Eekhoff, Dimitra Micha
Pathogenic variants in SPARC cause a rare autosomal recessive form of osteogenesis imperfecta (OI), classified as OI type XVII, which was first reported in 2015. Only six patient cases with this specific form of OI have been reported to date. The SPARC protein plays a crucial role in the calcification of collagen in bone, synthesis of the extracellular matrix, and the regulation of cell shape. In this
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How pain affect real life of children and adults with achondroplasia: A systematic review Eur. J. Med. Genet. (IF 1.9) Pub Date : 2023-09-26 Roberta Onesimo, Elisabetta Sforza, Maria Francesca Bedeschi, Chiara Leoni, Valentina Giorgio, Donato Rigante, Cristina De Rose, Eliza Maria Kuczynska, Domenico Marco Romeo, Osvaldo Palmacci, Luca Massimi, Matteo Porro, Michaela Veronika Gonfiantini, Angelo Selicorni, Anna Allegri, Mohamad Maghnie, Giuseppe Zampino
The clinical features of achondroplasia can cause acute self-limited pain that can evolve into chronic pain. Pain causes a low quality of life, in terms of physical, emotional, social, and school functioning in both adult and children with achondroplasia. We conducted a systematic review according to the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) statement to describe
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Clinical Genetics Assessment Triangle (CGAT): A simple tool to identify patients with genetic conditions Eur. J. Med. Genet. (IF 1.9) Pub Date : 2023-09-26 David Ferri-Rufete, Aitor López-González, Dídac Casas-Alba, Daniel Cuadras, Francesc Palau, Antonio Martínez-Monseny
Objective The objective of this study was to develop a simple tool for general physicians to promptly identify and refer pediatric patients with a higher probability of having a genetic condition. Study design This retrospective, descriptive study was conducted at a tertiary pediatric hospital's Clinical Genetics Unit from June 2019 to January 2020. We included patients under 18 years of age who visited
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Abnormal fetal ultrasound leading to the diagnosis of ADNP syndrome Eur. J. Med. Genet. (IF 1.9) Pub Date : 2023-09-25 Jessica Rosenblum, Lennart Van der Veeken, Michael Aertsen, Marije Meuwissen, Anna C. Jansen
ADNP syndrome, also known as the Helsmoortel-Van der Aa syndrome (HVDAS), is a neurodevelopmental disorder characterized by hypotonia, developmental delay, and intellectual disability. Diagnosis is typically made postnatally, and little is known about prenatal presentation of the disorder. We report a child who presented with intrauterine growth restriction, proportionate microcephaly, and an abnormal
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Combination of osteogenesis imperfecta and hypophosphatasia in three children with multiple fractures, low bone mass and severe osteomalacia, a challenge for therapeutic management Eur. J. Med. Genet. (IF 1.9) Pub Date : 2023-09-25 Nadja Fratzl-Zelman, Agnès Linglart, Kim Bin, Frank Rauch, Stéphane Blouin, Régis Coutant, Aurélie Donzeau
Osteogenesis imperfecta (OI) and hypophosphatasia (HPP) are rare skeletal disorders caused by mutations in the genes encoding collagen type I (COL1A, COL1A2) and tissue-non-specific isoenzyme of alkaline phosphatase (ALPL), respectively. Both conditions result in skeletal deformities and bone fragility although bone tissue abnormalities differ considerably. Children with OI have low bone mass and hypermineralized
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Life span care for patients with skeletal dysplasia: A roadmap Eur. J. Med. Genet. (IF 1.9) Pub Date : 2023-09-25 Wouter H. Nijhuis, Marjolein Verhoef, Ralph J.B. Sakkers
Patients with skeletal dysplasias usually experience health related problems in different parts and systems of the body. Therefore, they face challenges in multiple domains of functioning and health. To address these different domains, interdisciplinary care should be the standard for these patients. The basic algorithm of interdisciplinary care can be similar for patients with different skeletal dysplasias