Late onset spinal motor neuronopathy is caused by mutation in CHCHD10. Issue 1 (12th December 2014)

• Record Type: Journal Article
• Authors: Penttilä, Sini; Jokela, Manu; Bouquin, Heidi; Saukkonen, Anna Maija; Toivanen, Jari; Udd, Bjarne
• Is Part Of: Annals of neurology. Volume 77:Issue 1(2015:Jan.)
• Page Start: 163
• Page End: 172
• Publication Date: 2014-12-12
• Subjects: Neurology -- Periodicals; Pediatric neurology -- Periodicals; Nervous system -- Surgery -- Periodicals; 616.8
• DOI: 10.1002/ana.24319
• Languages: English
• ISSNs: 0364-5134

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <sec id="ana24319-sec-0001" sec-type="section"> <title>Objective</title> <p>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.</p> </sec> <sec id="ana24319-sec-0002" sec-type="section"> <title>Methods</title> <p>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.</p> </sec> <sec id="ana24319-sec-0003" sec-type="section"> <title>Results</title> <p>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 <italic>CHCHD10</italic> was identified. The mutation was shown to segregate with the disease in 55 patients from 17 families.</p> </sec> <sec id="ana24319-sec-0004" sec-type="section"> <title>Interpretation</title> <p>Mutation c.197G>T p.G66V in <italic>CHCHD10</italic> 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 <italic>CHCHD10</italic> gene is largely important for the motor and cognitive neuronal systems. ANN NEUROL 2015;77:163–172</p> </sec> </abstract>