常染色体隐性遗传性远端肾小管酸中毒患儿ATP6V0A4和ATP6V1B1基因突变分析

目的 分析常染色体隐性遗传性远端肾小管酸中毒(rdRTA)患儿ATP6V0A4和ATP6V1B1基因的突变,进行基因型和表型的相关性研究.方法 PCR扩增基因组DNA,直接测序分析来自3个家系3例患儿的ATP6V0A4和ATP6V1B1基因的突变位点,选取不相关的100例健康人作为对照.结果 1例患儿携带ATP6V0A4基因的1个新的纯合无义突变(p.R194X);1例患儿携带ATP6V1B1基因1个新的杂合无义突变(p.R114X)和1个已经报道过的杂合突变p.I386fsX441；第3例患儿未发现以上2个基因的突变.结论 对中国rdRTA患者基因突变分析有利于了解该类疾病的基因型和表型的相关性,增强临床医生对该类疾病的认识和治疗.

Mutation analysis of ATP6V0A4 and ATP6V1B1 gene in autosomal recessive distal renal tubular acidosis children

Objective To analyze and identify the mutations of ATP6V0A4 and ATP6V1B1 gene in autosomal recessive distal renal tubular acidosis (rdRTA) children, and study the association of genotype and phenotype. Methods Genome DNA was amplified by PCR. Mutations of ATP6V0A4 and ATP6V1B1 gene in 3 children from 3 families were examined by direct sequencing. One hundred unrelated healthy subjects were selected to evaluate all mutations found in this study. Results A novel homozygous nonsense mutation was identified in ATP6V0A4 gene in one child, and a novel heterozygous nonsense variant and a frame-shift alteration were found in another child. No mutation of both genes was found in the third child. Conclusions Study of mutant genes of rdRTA in Chinese patients is helpful to understand the association in genotype and phenotype and increase the level of cognition and treatment to this disease.