RT Journal Article
T1 Primary distal renal tubular acidosis: novel findings in patients studied by next-generation sequencing.
A1 Gómez, Juan
A1 Gil-Peña, Helena
A1 Santos, Fernando
A1 Coto, Eliecer
A1 Arango, Ana
A1 Hernandez, Olaya
A1 Rodríguez, Julián
A1 Nadal, Inmaculada
A1 Cantos, Virginia
A1 Chocrón, Sara
A1 Vergara, Inés
A1 Madrid, Álvaro
A1 Vazquez, Carlos
A1 González, Luz E
A1 Blanco, Fiona
AB Primary distal renal tubular acidosis (DRTA) is a rare disease caused by loss-of-function mutations in at least three genes (ATP6V0A4, ATP6V1B1, and SLC4A1) involved in urinary distal acidification. The next-generation sequencing (NGS) technique facilitates the search for mutations in DRTA patients and helps to characterize the genetic and clinical spectrum of the disease. Ten DRTA patients were studied. They had normal serum anion gap (AG), metabolic acidosis with simultaneous positive urinary AG, and inability to maximally acidify the urine. The exons of the three genes were sequenced in two pools by ultrasequencing. Putative mutations were confirmed by corresponding Sanger sequencing of each exon. We found 13 mutations in nine patients. ATP6V0A4: Intron16+2insA; p.R807Q; p.Q276fs; p.P395fs; Intron7-2T>C. ATP6V1B1: p.I386fs; p.R394Q. SLC4A1: p.V245M; p.R589C; p.R589H; p.G609A. One case was a compound heterozygous with a known mutation in ATP6V1B1 (p.G609R) and a pathogenic variation at SLC4A1 (p.E508K). One patient was negative for mutations. This study evidences that NGS is labor and cost effective for the analysis of DRTA genes. Our results show for the first time SLC4A1 gene mutations in Spanish patients and disclose that compound heterozygosity at two different genes can be responsible for DRTA.
YR 2015
FD 2015-11-16
LK http://hdl.handle.net/10668/9622
UL http://hdl.handle.net/10668/9622
LA en
DS RISalud
RD Apr 10, 2025