A novel homocygous missense mutation of the gene for KCNJ1 in Bartter syndrome type II

DELLA VEDOVA MC; MARSA S.M; SIEWERT S.; GIORDANO M

Foz do Iguazu

Congreso; XXII Congreso Internacional de Genetica; 2018

Sociedad Brasilera de Genética (SBG)

This report concerns an 11-year-old female. She showed immediate perinatal/postnatal problems: polyhydramnios, pulmonary hypertension, feeding difficulties, polyuria, polydipsia, hypokalemia, metabolic alkalosis and hypercalciuria, without other alteration of the internal environment. She was diagnosed with a clinical diagnosis of neonatal Bartter Syndrome. The patient was started with treatment: hydrochlorothiazide, indomethacin, potassium citrate, and zinc/iron/vitamin. After three years of age, she presented alterations: metabolic alkalosis, severe hypokalemia that improve and remain stable with treatment, hypercalciuria that does not improve despite treatment. She had nephrocalcinosis, growth retardation and intelligence normal. Next-generation sequencing technology was used; the Bartter Syndrome Panel consists of sequence analysis of genes associated: BSND, CASR,CLCNKA, CLCNKB, GNA11, KCNJ1, SLC12A1 and SLC12A3. The panel is targeting all protein coding exons and exon-intron boundaries of all target genes. It also covers a number of mutations located outside these coding regions, detect INDELs, includes OS-Seq Del/Dup (CNV) Analysis for the same genes as listed above. It should be used to diagnose deletions and duplications in protein-coding regions of the genes included in the panel. Bioinformatical analysis of the results using international data bases enabled association of mutations with clinical signs.Sequence analysis identified a homozygous missense variant in the KCNJ1 gene c.833T>G results in p.Leu278Cys. Mutation nomenclature is based on GenBank accession NM_000220.4 (KCNJ1) with nucleotide one being the first nucleotide of the translation initiation codon ATG. It has not been observed in large reference population cohorts of Genome Aggregation Database. The variant has not been reported in the literature or in the disease-related variation databases ClinVar or HGMD.