Clinical and genetic phenotypes of an autosomal recessive spinocerebellar ataxia-10 patient due to ANO10 gene mutations / 中华神经科杂志

ABSTRACT

Objective:To investigate the clinical phenotypes, imaging features and pathogenic variants of ANO10 gene related autosomal recessive spinocerebellar ataxia-10 (SCAR10).Methods:A cohort of 30 probands of autosomal recessive cerebellar ataxia pedigrees from China-Japan Friendship Hospital from 2018 to 2020 were collected. Friedreich ataxia and other causes of acquired ataxia were excluded, then probands were detected by whole-exome sequencing (WES), and potential pathogenic variants were confirmed by Sanger sequencing and validated in all family members. Clinical phenotypes and auxiliary examinations of the patients were analyzed in detail.Results:A pedigree of SCAR10 caused by ANO10 gene mutations was identified through WES. The 40-year-old male proband of this pedigree carried compound heterozygous mutations c.1219-2A>C and c.1163-2A>G of the ANO10 gene, both of which were novel mutations, and Sanger sequencing revealed these two mutations were respectively inherited from his healthy parents. Bioinformatic analysis predicted these two mutations were pathogenic. The proband exhibited progressive unsteady walk, dysarthria, mild cognitive impairment. His plasma total coenzyme Q 10 was decreased (0.76 μg/ml). Brain magnetic resonance imaging showed remarkable cerebellar atrophy. Conclusions:Through WES, a SCAR10 patient caused by novel compound heterozygous mutations of ANO10 gene was identified, which is rare in China. The main clinical manifestation was progressive cerebellar ataxia and cognitive decline, and brain image showed remarkable cerebellar atrophy.