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.
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.
Authors: Nicolai Marroquin; Sebastian Stranz; Kathrin Müller; Thomas Wieland; Wolfgang P Ruf; Sarah J Brockmann; Karin M Danzer; Guntram Borck; Annemarie Hübers; Patrick Weydt; Thomas Meitinger; Tim-Matthias Strom; Angela Rosenbohm; Albert C Ludolph; Jochen H Weishaupt Journal: Brain Date: 2015-09-11 Impact factor: 13.501
Authors: Samir Abdelkarim; Sarah Morgan; Vincent Plagnol; Ching-Hua Lu; Gary Adamson; Robin Howard; Andrea Malaspina; Richard Orrell; Nikhil Sharma; Katie Sidle; Jan Clarke; Nick C Fox; Martin N Rossor; Jason D Warren; Camilla N Clark; Jonathan D Rohrer; Elizabeth M C Fisher; Simon Mead; Alan Pittman; Pietro Fratta Journal: Brain Date: 2015-09-11 Impact factor: 13.501
Authors: Tian Liu; Jung-A A Woo; Mohammed Zaheen Bukhari; Patrick LePochat; Ann Chacko; Maj-Linda B Selenica; Yan Yan; Peter Kotsiviras; Sara Cazzaro Buosi; Xingyu Zhao; David E Kang Journal: FASEB J Date: 2020-05-05 Impact factor: 5.191
Authors: S R Burstein; F Valsecchi; H Kawamata; M Bourens; R Zeng; A Zuberi; T A Milner; S M Cloonan; C Lutz; A Barrientos; G Manfredi Journal: Hum Mol Genet Date: 2018-01-01 Impact factor: 6.150