open access
A missense mutation in DYNC1H1 gene causing spinal muscular atrophy – Lower extremity, dominant
Affiliations- Department of Neurology, Royal Hallamshire Hospital, Sheffield Teaching Hospitals NHS Foundation Trust, Glossop Road, Sheffield, United Kingdom
- Greater Manchester Neurosciences Centre, Salford Royal NHS Foundation Trust, Stott Lane, Salford, United Kingdom
open access
Abstract
Spinal muscular atrophy (SMA) is a hereditary neuromuscular disorder, which causes progressive muscle weakness and in severe cases respiratory failure and death. Although the majority of the SMA cases are autosomal recessive, there is an autosomal dominant variant of SMA that primarily affects the lower extremities, known as ‘spinal muscular atrophy – lower extremity, dominant’ (SMALED). Mutations in the Dynein Cytoplasmic 1 Heavy Chain 1 (DYNC1H1) gene were the first to be associated with SMALED. Here we report a family with SMALED caused by a pathogenic heterozygous missense c.1809 A>T, p.glu603Asp mutation in DYNC1H1. The main clinical features were congenital hip displacement, talipes, delayed motor development, wasting and weakness in lower limbs with relative sparing of upper extremities and very slow disease progression.
SMALED is extremely rare and only a handful of families have been reported. Over the years other phenotypes including Charcot Marie Tooth type 2 and hereditary mental retardation with cortical neural migration defects have also been reported to be caused by DYNC1H1 mutations.
This report aims to increase our awareness of SMALED and various other phenotypes associated with mutations in this gene.
Abstract
Spinal muscular atrophy (SMA) is a hereditary neuromuscular disorder, which causes progressive muscle weakness and in severe cases respiratory failure and death. Although the majority of the SMA cases are autosomal recessive, there is an autosomal dominant variant of SMA that primarily affects the lower extremities, known as ‘spinal muscular atrophy – lower extremity, dominant’ (SMALED). Mutations in the Dynein Cytoplasmic 1 Heavy Chain 1 (DYNC1H1) gene were the first to be associated with SMALED. Here we report a family with SMALED caused by a pathogenic heterozygous missense c.1809 A>T, p.glu603Asp mutation in DYNC1H1. The main clinical features were congenital hip displacement, talipes, delayed motor development, wasting and weakness in lower limbs with relative sparing of upper extremities and very slow disease progression.
SMALED is extremely rare and only a handful of families have been reported. Over the years other phenotypes including Charcot Marie Tooth type 2 and hereditary mental retardation with cortical neural migration defects have also been reported to be caused by DYNC1H1 mutations.
This report aims to increase our awareness of SMALED and various other phenotypes associated with mutations in this gene.
Keywords
SMA, SMALED, DYNC1H1, EMG
About this articleTitle
A missense mutation in DYNC1H1 gene causing spinal muscular atrophy – Lower extremity, dominant
Journal
Neurologia i Neurochirurgia Polska
Issue
Pages
293-297
Published online
2017-12-14
Page views
408
Article views/downloads
495
DOI
10.1016/j.pjnns.2017.12.004
Bibliographic record
Neurol Neurochir Pol 2018;52(2):293-297.
Keywords
SMA
SMALED
DYNC1H1
EMG
Authors
Joyutpal Das
James B. Lilleker
Kavaldeep Jabbal
John Ealing
