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COLQ-related congenital myasthenic syndrome: An integrative view

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Abstract

Congenital myasthenic syndromes are inherited disorders caused by mutation in components of the neuromuscular junction and manifest early in life. Mutations in COLQ gene result in congenital myasthenic syndrome. Here, we present the analysis of data from 209 patients from 195 unrelated families highlighting genotype-phenotype correlation. In addition, we describe a COLQ homozygous variant a new patient and discuss it utilizing the Phyre2 and I-TASSER programs. Clinical, molecular genetics, imaging (MRI), and electrodiagnostic (EEG, EMG/NCS) evaluations were performed. Our data showed 89 pathogenic/likely pathogenic variants including 35 missenses, 21 indels, 14 nonsense, 14 splicing, and 5 large deletions variants. Eight common variants were responsible for 48.46% of those. Weakness in proximal muscles, hypotonia, and generalized weakness were detected in all individuals tested. Apart from the weakness, extensive clinical heterogeneity was noted among patients with COLQ-related patients based on their genotypes—those with variants affecting the splice site exhibited more severe clinical features while those with missense variants displayed milder phenotypes, suggesting the role of differential splice variants in multiple functions within the muscle. Analyses and descriptions of these COLQ variants may be helpful in clinical trial readiness and potential development of novel therapies in the setting of established structure-function relationships.

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Acknowledgements

We would like to thank the personnels of Growth and Development Research Center and Cardiogenetic Research Laboratory, Rajaei Hospital.

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  1. Tina Eshaghian and Bahareh Rabbani contributed equally to this work.

Authors and Affiliations

  1. Growth and Development Research, Tehran University of Medical Sciences, Tehran, Iran

    Tina Eshaghian, Bahareh Rabbani, Reza Shervin Badv, Sahar Mikaeeli & Nejat Mahdieh

  2. Children’s Hospital Center, Pediatric Center of Excellence, Tehran University of Medical Center, Tehran, Iran

    Reza Shervin Badv & Behdad Gharib

  3. Johns Hopkins All Children’s Hospital, Division of Neurology, 601 5th Street S, St. Petersburg, FL, 33701, USA

    Stanley Iyadurai

  4. Cardiogenetic Research Center, Rajaie Cardiovascular Medical and Research Center, Iran University of Medical Sciences, Niayesh-Vali asr Intersection, Tehran, Iran

    Nejat Mahdieh

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  1. Tina Eshaghian
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Eshaghian, T., Rabbani, B., Badv, R.S. et al. COLQ-related congenital myasthenic syndrome: An integrative view. Neurogenetics 24, 189–200 (2023). https://doi.org/10.1007/s10048-023-00719-7

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