Homozygosity mapping and mutation analysis of a consanguineous marriage family with autosomal recessive cerebellar ataxia
10.3760/cma.j.issn.1006-7876.2015.05.011
- VernacularTitle:近亲婚配的常染色体隐性遗传共济失调家系致病基因纯合性定位及突变分析
- Author:
Ying HAO
;
Weihong GU
;
Yuanyuan CHEN
;
Jin ZHANG
- Publication Type:Journal Article
- Keywords:
Autosomal recessive cerebellar ataxia;
Consanguineous marriage;
Homozygosity mapping;
Oculomotor apraxia
- From:
Chinese Journal of Neurology
2015;48(5):400-405
- CountryChina
- Language:Chinese
-
Abstract:
Objective To identify the pathogenic gene for a Chinese Han consanguineous marriage family with autosomal recessive cerebellar ataxia by homozygosity mapping and mutation analysis.Methods Six members of the family were enrolled in this study,including 3 patients,the unaffected sibling and their parents of first cousin marriage.After excluding GAA repeats mutation of FXN gene,whole-genome single nucleotide polymorphism (SNP) microarray scanning and homozygosity mapping were performed to localize the candidate gene.The coding regions and intronic flanking sequences of the candidate genes were analyzed.Results Four candidate regions were identified,including 2p25.3,9q22.2-34.3,13q12.3-14.3 and 17p13.The SETX gene localizing in 9q22.2-34.3 that is responsible for ataxia with oculomotor apraxia 2 was analyzed at first.There were 4 mutations in exon 10,including three missense mutations (c.3576T ＞ G,p.D1192E ; c.3754G ＞ A,p.G1252R; c.4156A ＞ G,p.I1386V) and a deletion mutation (c.5084_5087delAGTC,p.Q1695_S1696del).Three patients were homozygous of the 4 mutations,an unaffected sibling was normal,and their parents were heterozygous of 4 mutations.Conclusions The pathogenic haplotype comprising four mutations of the SETX gene was identified in the consanguinity family.c.5084_5087delAGTC (p.Q1695_S1696del) is a novel mutation.The affected individuals of this family were characterized by mild phenotype and slow progress without oculomotor apraxia,indicating the clinical variability of the disease.
