Abstract
Aminoacyl-tRNA synthetases (ARSs) aminoacylate tRNA molecules with their cognate amino acid, enabling information transmission and providing substrates for protein biosynthesis. They also take part in nontranslational functions, mediated by the presence of other proteins domains. Mutations in ARS genes have been described as responsive to numerous factors, including neurological, autoimmune, and oncological. Variants of the ARS genes, both in heterozygosity and homozygosity, have been reported to be responsible for different pathological pictures in humankind. We present the case of a patient referred in infancy for failure to thrive and acquired microcephaly (head circumference: -5 SD). During follow-up we highlighted: dysphagia (which became increasingly severe until it became incompatible with oral feeding, with gastrostomy implantation, resulting in resolution of feeding difficulties), strabismus, hypotonia. NCV (Nerve Conduction Velocity) showed four limbs neuropathy, neurophysiological examination performed at 2 years of age mainly sensory and demyelinating. Exome sequencing (ES) was performed, detecting two novel compound heterozygous variants in the NARS1 gene (OMIM *108410): NM_004539:c.[662 A > G]; [1155dup], p.[(Asn221Ser)]; [(Arg386Thrfs*19)], inherited from mother and father respectively. In this article, we would like to focus on the presence of progressive dysphagia and severe neurodevelopmental disorder, associated with two novel variants in the NARS1 gene.
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Data are available by contacting the corresponding author by email, upon reasonable request.
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Acknowledgements
This work was generated within the European Reference Network on Rare Congenital Malformations and Rare Intellectual Disability (ERN-ITHACA) (EU Framework Partnership Agreement ID: 3HP-HP-FPA ERN-01-2016/739516). The authors also wish to thank the patient’s family members for their cooperation in providing the medical data for this publication. We thank the nurses from the Child Neurology and Psychiatry Unit and Medical Genetics Unit for their cooperation.
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Conceptualization, CAC, GC, FC, CS, CF; clinical data collection and data curation, CAC, GC, CS, FC, SGC, AL, CS, DF, SR, AC, LG, CF; writing—original draft preparation, CAC, GC, CS, FC, SGC, CS; writing—review and editing, CAC, GC, CS, SGC; supervision, LG, CF. All authors have read and agreed to the published version of the manuscript.
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Cesaroni, C.A., Contrò, G., Spagnoli, C. et al. Early-onset dysphagia and severe neurodevelopmental disorder as early signs in a patient with two novel variants in NARS1: a case report and brief review of the literature. Neurogenetics (2024). https://doi.org/10.1007/s10048-024-00760-0
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DOI: https://doi.org/10.1007/s10048-024-00760-0