Mutation analysis of 5 children with primary distal renal tubular acidosis
10.3760/cma.j.issn.1001-7097.2018.06.004
- VernacularTitle:五例原发性远端肾小管酸中毒患儿的基因突变分析
- Author:
Ruixiao ZHANG
1
;
Yanhua LANG
;
Yanxia GAO
;
Zeqing CHEN
;
Cui WANG
;
Jingru LU
;
Leping SHAO
Author Information
1. 266003,青岛大学附属医院肾内科
- Keywords:
Acidosis,renal tubular;
Mutation;
SLC4A 1;
ATP6V0A4;
ATP6V 1B1
- From:
Chinese Journal of Nephrology
2018;34(6):410-417
- CountryChina
- Language:Chinese
-
Abstract:
Objective To analyze the mutations of causal genes in 5 children with primary distal renal tubular acidosis (dRTA),and explore their association of genotype and phenotype,so as to raise the awareness of the disease.Methods The whole exome sequencing was used to identify mutations in these 5 children from 5 families.Results A total of 4 different mutations of ATP6V0A4 gene were found in 2 dRTA children,including a novel heterozygous intron mutation (c.639 + 1G＞ A),a reported heterozygous nonsense variant (c.580C ＞T,p.Arg194*) and 2 novel heterozygous duplications (c.1504dupT,p.Tyr502Leufs*22;c.2351dupT,p.Phe785Ilefs*28).Two novel heterozygous missense mutations of ATP6V 1B 1 gene (c.409C ＞ T,p.Pro 137Ser;c.904C ＞ T,p.Arg302Trp) were identified in the third child,and a heterozygous missense mutation of SLC4A1 gene (c.1765C ＞ A,p.Arg589Ser) previously reported was found in the fourth child.No mutation of the dRTA-related causal genes was found in the fifth child.Furthermore,the mutations of causal genes in each of the first three children were compound heterozygous,which were consistent with the autosomal recessive inheritance pattern,and the variant from the fourth child was de novo.Conclusions The present study has found 7 mutations,including 5 novel variants,which enriches the human gene mutation database (HGMD) and contributes to a better understanding of the disease mechanisms.
