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Ann Neurol. 2015 Jan;77(1):163-72. doi: 10.1002/ana.24319. Epub 2014 Dec 12.

Late onset spinal motor neuronopathy is caused by mutation in CHCHD10.

Author information

1
Neuromuscular Research Center, Tampere University and University Hospital, Tampere.

Abstract

OBJECTIVE:

A study was undertaken to identify the responsible gene defect underlying late onset spinal motor neuronopathy (LOSMoN/SMAJ; Online Mendelian Inheritance in Man #615048), an autosomal dominant disease mapped to chromosome 22q11.2.

METHODS:

The previous genetic linkage approach by microsatellite haplotyping was continued in new families. A whole genome sequencing was performed to find all possibly pathogenic mutations in the linked area. The detected variations were verified by Sanger sequencing.

RESULTS:

Six new SMAJ families were identified based on the unique founder haplotype. A critical recombination in 1 family restricted the linked area to 727kb between markers SHGC-106816 and D22S345. In whole genome sequencing a previously unknown mutation c.197G>T p.G66V in CHCHD10 was identified. The mutation was shown to segregate with the disease in 55 patients from 17 families.

INTERPRETATION:

Mutation c.197G>T p.G66V in CHCHD10 is the cause of the lower motor neuron syndrome LOSMoN/SMAJ. During the preparation of this article other mutations were reported to cause frontotemporal dementia-amyotrophic lateral sclerosis syndrome, indicating that the CHCHD10 gene is largely important for the motor and cognitive neuronal systems.

PMID:
25428574
DOI:
10.1002/ana.24319
[Indexed for MEDLINE]

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