Mutation analysis and phenotypic investigation in patients with primary distal renal tubular acidosis
10.3760/cma.j.cn441217-20201009-00106
- VernacularTitle:原发性远端肾小管酸中毒患者的基因突变分析和临床表型研究
- Author:
Wencong GUO
1
;
Bingzi DONG
;
Ruixiao ZHANG
;
Zhiying LIU
;
Qing XIN
;
Xiaomeng SHI
;
Yue HAN
;
Yanhua LANG
;
Xiangzhong ZHAO
;
Yan CAI
;
Qingqing YOU
;
Yan SUN
;
Huasheng DU
;
Leping SHAO
Author Information
1. 青岛大学附属市立医院肾内科，青岛 266071
- Keywords:
Acidosis, renal tubular;
Mutation;
Genotype;
Phenotype;
SLC4A1 gene;
ATP6V0A4 gene;
ATP6V1B1 gene
- From:
Chinese Journal of Nephrology
2021;37(9):712-722
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To analyze the gene variants in patients with primary distal renal tubular acidosis (dRTA), and explore the correlation between the genotype and phenotype.Methods:The Sanger direct sequencing or whole-exome sequencing was used to identify causal variants and the variation pathogenicity was evaluated according to 2015 American College of Medical Genetics and Genomics (ACMG) standards and guidelines in 44 dRTA patients (37 families) diagnosed in the Affiliated Qingdao Municipal Hospital of Qingdao University and the Affiliated Hospital of Qingdao University from April 2010 to September 2020. The clinical features of the patients were summarized, and the correlation between the genotype and phenotype was investigated.Results:Seven variants of SLC4A1 gene, 17 variants of ATP6V0A4 gene, and 15 variants of ATP6V1B1 gene were identified in 44 patients with dRTA, and of which 11 variants were new ones. According to ACMG guidelines, the pathogenic, likely pathogenic, benign variants among the 39 variants were 22, 16 and 1, respectively. Nine patients were autosomal dominant hereditary dRTA caused by SLC4A1 gene mutation, 4 patients with autosomal recessive hereditary dRTA complicated with Southeast Asian ovalocytosis and anemia were caused by SLC4A1 gene mutation, and 14 patients caused by ATP6V0A4 gene mutation and 8 patients caused by ATP6V1B1 gene mutation were autosomal recessive hereditary dRTA; Two children with dRTA were found to carry one monoallelic defect in ATP6V1B1, and no causal gene mutation was identified in 7 patients. One patient showed incomplete dRTA, and the other 43 patients showed complete dRTA. The prevalence of sensory neural hearing loss caused by ATP6V0A4 and ATP6V1B1 mutation were 2/14 and 6/10 respectively. The frequency of chronic kidney disease in adults, children and infants were 4/4, 2/4, and 1/36, separately. After the drug treatment based on potassium citrate and sodium citrate, the growth and development (28/40) and electrolyte disturbance (41/44) of most patients were significantly improved. Conclusions:The present study has identified 39 variants of SLC4A1, ATP6V0A4 and ATP6V1B1 genes in 44 patients with dRTA, including 11 novel ones. There is a close relationship between genotype and phenotype in dRTA patients and most patients' conditions were improved after proper treatment. This study enriches the human gene mutation database and provides valuable references for diagnosis, treatment and genetic counseling in patients with dRTA.
