A novel SLC4A1 variant in an autosomal dominant distal renal tubular acidosis family with a severe phenotype.
Mutations in SLC4A1, encoding the chloride-bicarbonate exchanger AE1, cause distal renal tubular acidosis (dRTA), a disease of defective urinary acidification by the distal nephron. We searched for SLC4A1 gene mutations in six patients from a Chinese family with a severe phenotype of dRTA (growth impairment, severe metabolic acidosis, with/or without gross nephrocalcinosis and renal impairment). All coding regions of kidney isoform of AE1, including intron-exon boundaries, were analyzed using PCR followed by direct sequence analysis. A novel 1-bp duplication at nucleotide 2713 (c.2713dupG, band 3 Qingdao) in exon 20 of SLC4A1 in this family was identified by direct sequencing analysis. This duplication alters the encoded protein through codon 905, and results in a reading frame for 15 extra condons (instead of 8) before the new stop condon at position 919 (p.Asp905Glyfs15). We suggest that RTA should be considered as a diagnostic possibility in adult subjects with nephrocalcinosis and chronic renal insufficiency, and family survey should be carefully performed.
Department of Nephrology, Affilated Hospital of Qingdao University School of Medicine, #16, Jiangsu Road, Qingdao 266003, People's Republic of China. lepingshao@163.com
Leping
L
Shao
Yan
Y
Xu
Qian
Q
Dong
Yanhua
Y
Lang
Shaoheng
S
Yue
Zhimin
Z
Miao
D000141:Acidosis, Renal Tubular / Q000175:diagnosis / Q000235:genetics*; D000368:Aged; D001457:Anion Exchange Protein 1, Erythrocyte / Q000235:genetics*; D005799:Genes, Dominant; D006801:Humans; D009154:Mutation; D009397:Nephrocalcinosis / Q000235:genetics; D010375:Pedigree; D010641:Phenotype
D001457:Anion Exchange Protein 1, Erythrocyte; C454201:SLC4A1 protein, human