Identification of CHCHD10 Mutation in Chinese Patients with Alzheimer Disease

Abstract

CHCHD10 gene has been identified to be associated with frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS). Considering the clinical phenotype and pathology characterization were overlapped between FTD and Alzheimer disease (AD), and so far, no systematic analysis of CHCHD10 mutation was conducted in patients with AD in Asian population. Therefore, we screened of all exons in CHCHD10 in a cohort of 484 AD patients (60 with family history) from Mainland China. A heterozygous variant p.A35D (c.104C>A), previously reported in a patient with FTD in Italian population, was identified in a female patient with sporadic LOAD. The age at onset of mutation carrier was 86, presented as typical amnestic dementia. The mutation was found to be deleterious according to in silico predictions and excluded in 500 ethnically and geographically matched controls. Our finding revealed the clinical manifestations of variant p.A35D (c.104C>A) in a LOAD case and indicated that CHCHD10 mutation was presented in different types of dementia.

Twin CHCH Proteins, CHCHD2, and CHCHD10: Key Molecules of Parkinson’s Disease, Amyotrophic Lateral Sclerosis, and Frontotemporal Dementia

“…( Lower ) Coding variants in FTD patients [23,25] are in green, in patients with ALS [21,23,24], CMT2 [26,27], or SMAJ [28] in red, in ALS–FTD patients [8,22] and patients with motor neuron disease [21] in black, and in mitochondrial myopathy patients [29] in blue. Potential risk variants found in ALS [41,42,43,44,45], FTD [44], FTD with PD pathology [25], AD [46], and ALS–FTD [22] patients are in grey. Note that R15S and G58R were found in cis and there is the possibility that one or the other but not both are pathogenic [29].…”

Identification of CHCHD2 mutations in patients with Alzheimer's disease, amyotrophic lateral sclerosis and frontotemporal dementia in China

“…Neuroradiological examinations for example MRI, was assessed with patients diagnosed as probable or possible AD and FTD in this study. We have excluded AD, FTD and ALS patients carrying disease-causing gene like PSEN1, PSEN2, APP, MAPT, GRN, C9orf72, TREM2, CHCHD10, SOD1, TARDBP, FUS (3,(16)(17)(18)(19)(20). Additionally, the APOE genotype was available for all AD patients.…”

“…Mutations of CHCHD genes have been identified to be associated with various human neurodegenerative diseases (1). CHCHD10, which is a CHCHD protein, was identified to be associated with amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD) and Alzheimer's disease (AD) in Chinese population (2,3). Recently, the CHCHD2 gene was identified as a possible causative gene for Parkinson's disease (PD).…”

The Genetics of Alzheimer’s Disease in the Chinese Population

“…The Coiled Coil-Helix-Coiled-Coil-Helix domain containing 10 (CHCHD10) gene was reported to be a risk gene for FTD and amyotrophic lateral sclerosis in Europe [130], two novel mutations (63C > T, no amino acid change; 71G > A, p.P24L) were also found in Chinese FTD patients [86]. The p.A35D variant of CHCHD10 was reported in a patient with sporadic LOAD in China [87].…”