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Child Neurol Open. 2016 Sep 26;3:2329048X16669912. doi: 10.1177/2329048X16669912. eCollection 2016 Jan-Dec.

Further Validation of the SIGMAR1 c.151+1G>T Mutation as Cause of Distal Hereditary Motor Neuropathy.

Lee JJY1,2,3, van Karnebeek CDM1,2,3,4, Drögemoller B3,5, Shyr C1,2,3, Tarailo-Graovac M1,2,3,5, Eydoux P2,3,6, Ross CJ1,2,3,5, Wasserman WW1,2,3,5, Björnson B3,7, Wu JK3,8.

Author information

1
Centre for Molecular Medicine and Therapeutics, Vancouver, British Columbia, Canada.
2
Treatable Intellectual Disability Endeavour in British Columbia, Vancouver, British Columbia, Canada.
3
BC Children's Hospital Research Institute, Vancouver, British Columbia, Canada.
4
Division of Biochemical Diseases, Department of Pediatrics, BC Children's Hospital, University of British Columbia, Vancouver, British Columbia, Canada.
5
Department of Medical Genetics, University of British Columbia, Vancouver, British Columbia, Canada.
6
Cytogenetics Laboratory, Department of Pathology and Laboratory Medicine, BC Children's Hospital, University of British Columbia, Vancouver, British Columbia, Canada.
7
Division of Pediatric Neurology, Department of Pediatrics, BC Children's Hospital, University of British Columbia, Vancouver, British Columbia, Canada.
8
Division of Hematology/Oncology/BMT, Department of Pediatrics, BC Children's Hospital, University of British Columbia, Vancouver, British Columbia, Canada.

Abstract

Distal hereditary motor neuropathies represent a group of rare genetic disorders characterized by progressive distal motor weakness without sensory loss. Their genetic heterogeneity is high and thus eligible for diagnostic whole exome sequencing. The authors report successful application of whole exome sequencing in diagnosing a second consanguineous family with distal hereditary motor neuropathy due to a homozygous c.151+1G>T variant in SIGMAR1. This variant was recently proposed as causal for the same condition in a consanguineous Chinese family. Compared to this family, the Afghan ethnic origin of our patient is distinct, yet the features are identical, validating the SIGMAR1 deficiency phenotype: progressive muscle wasting/weakness in lower and upper limbs without sensory loss. Rapid disease progression during adolescent growth is similar and may be due to SIGMAR1's role in regulating axon elongation and tau phosphorylation. Finally, the authors conclude that SIGMAR1 deficiency should be added to the differential diagnosis of distal hereditary motor neuropathies.

KEYWORDS:

SIGMAR1; dHMN; distal hereditary motor neuropathy; sigma-1 receptor; whole exome sequencing

Conflict of interest statement

Declaration of Conflicting Interests: The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

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