TOR1A variants cause a severe arthrogryposis with developmental delay, strabismus and tremor
Publish place: The Third International and 15th National Genetics Congress
Publish Year: 1397
نوع سند: مقاله کنفرانسی
زبان: English
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شناسه ملی سند علمی:
CIGS15_410
تاریخ نمایه سازی: 13 بهمن 1398
Abstract:
Background: Autosomal dominant torsion dystonia-1 is a disease with incomplete penetrance most often caused by an in-frame GAG deletion (p.Glu303del) in the endoplasmic reticulum luminal protein torsinA encoded by TOR1A.Findings: We report an association of the homozygous dominant disease-causing TOR1A p.Glu303del mutation, and a novel homozygous missense variant (p.Gly318Ser) with a severe arthrogryposis phenotype with developmental delay, strabismus and tremor in three unrelated families. All parents who were carriers of the TOR1A variant showed no evidence of neurological symptoms or signs, indicating decreased penetrance similar to families with autosomal dominant torsion dystonia-1. The results from cell assays demonstrate that the p.Gly318Ser substitution causes a redistribution of torsinA from the endoplasmic reticulum to the nuclear envelope, similar to the hallmark of the p.Glu303del mutation.Conclusion: Our study highlights that TOR1A mutations should be considered in patients with severe arthrogryposis and further expands the phenotypic spectrum associated with TOR1A.
Keywords:
TOR1A , Endoplasmic reticulum luminal protein torsinA , DYT1 dystonia , TOR1A p.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
Elham Keshavarz
Department of Radiology, Mahdieh Hospital, Shahid Beheshti University of Medical Science, Tehran, Iran.
Mehrshid Faraji Zonooz
Kariminejad-Najmabadi Pathology & Genetics Center, Tehran, Iran