TOR1A variants cause a severe arthrogryposis with developmental delay, strabismus and tremor
Publish place: 2nd International & 10th National Neurogenetic Congress,
Publish Year: 1396
نوع سند: مقاله کنفرانسی
زبان: English
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شناسه ملی سند علمی:
NGCMED10_024
تاریخ نمایه سازی: 16 تیر 1397
Abstract:
Introduction: Autosomal dominant torsion dystonia-1 is a disease withincomplete penetrance most often caused by an in-frame GAG deletion(p.Glu303del) in the endoplasmic reticulum luminal protein torsinA encodedby TOR1A.Methods: Wereport an association of the homozygous dominant diseasecausingTOR1Ap.Glu303del mutation, and a novel homozygous missensevariant (p.Gly318Ser) with a severe arthrogryposis phenotype withdevelopmental delay,strabismus and tremor in three unrelated families.Results: All parents who were carriers of the TOR1A variant showed noevidence of neurological symptoms or signs, indicating decreased penetrancesimilar to families with autosomal dominant torsion dystonia-1. The resultsfrom cell assays demonstrate that the p.Gly318Ser substitution causes aredistribution of torsinA from the endoplasmic reticulum to the nuclearenvelope, similar to the hallmark of the p.Glu303del mutation.Conclusion: Our study highlights that TOR1A mutations should be consideredin patients with severe arthrogryposis and further expands the phenotypicspectrum associated with TOR1A.
Keywords:
TOR1A , Endoplasmic reticulum luminal protein torsinA , DYT1 dystonia , TOR1Ap.Glu303del , Severe arthrogryposis
Authors
Ariana Kariminejad
Kariminejad-Najmabadi Pathology & Genetics Center, Tehran, Iran
Martin Dahl-Halvarsson
Department of Pathology, University of Gothenburg, Sahlgrenska University Hospital, Sweden
Gianina Ravenscroft
Centre for Medical Research, The University of Western Australia and the Harry Perkins Institute for Medical Research, Nedlands, Western Australia, Australia
Fariba Afroozan
Kariminejad-Najmabadi Pathology & Genetics Center, Tehran, Iran