A novel homozygous mutation in the SACS gene causing autosomal recessive spastic ataxia of Charlevoix-Saguenay: study of a family
10.3760/cma.j.cn113694-20230918-00172
- VernacularTitle:SACS基因新发纯合突变致Charlevoix-Saguenay型常染色体隐性痉挛性共济失调一家系研究
- Author:
Haijiang LI
1
;
Ailan PANG
;
Yanlan ZHANG
;
Yanbing HAN
Author Information
1. 昆明医科大学第一附属医院神经内科 云南省神经系统疾病临床医学研究中心，昆明650032
- Keywords:
Ataxia;
SACS gene;
Mutation;
Whole exon sequencing
- From:
Chinese Journal of Neurology
2024;57(6):593-599
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To report the clinical and genetic characteristics of autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) induced by a new homozygous mutation in the SACS gene, and to improve the clinicians′ recognition of the disease. Methods:Detailed nervous system physical examination was performed on the patient and his parents from a consanguineous family admitted to the Genetics and Metabolism Clinic of the Department of Neurology, the First Affiliated Hospital of Kunming Medical University in March 2022. The peripheral blood DNA of the patient and his parents was extracted, and whole exon sequencing (WES) was performed on the patient and his parents using second-generation sequencing technology. The mutation sites were verified by Sanger sequencing, and the mutation sites were analyzed by software.Results:The 18-year-old Han ethnic male patient developed a progressive stiffness of his bilateral lower limbs and gait unsteadiness since the age of 3. He had pyramidal tract sign in his bilateral lower limbs, cerebellar ataxia, pes cavus and hammer toes. Brain magnetic resonance imaging (MRI) showed symmetrical low signal of bilateral pons, cerebellar atrophy and thinning of corpus callosum in T 2WI and T 2 fluid attenuated inversion recovery (FLAIR) sequences. Neuroelectrophysiological examination showed sensory motor peripheral neuropathy. Ophthalmic examination revealed concomitant exotropia and ametropia in both eyes. WES revealed a homozygous variant of c.6958T>C (p.Tyr2320His) in exon 10 of the SACS gene of the patient, and his parents were heterozygous variant carriers confirmed by Sanger sequencing. The variant was classified as possibly pathogenic (PM1+PM2+PP3+PP4) according to the American Society for Medical Genetics and Genomics. The patient was clearly diagnosed as ARSACS caused by homozygous mutation of c.6958T>C in the SACS gene. Conclusions:A novel pathogenic variant (c.6958T>C) in the SACS gene identified in this study leads to the manifestation of ARSACS. The primary clinical manifestations include cerebellar ataxia, pyramidal tract signs, and sensorimotor peripheral neuropathy. Head MRI examination of T 2WI and T 2FLAIR sequences with symmetrical low signal on both sides of the pons helps to narrow down the scope of differential diagnosis.
