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.