A novel SLC12A1 mutation in Bedouin kindred with antenatal Bartter syndrome type I.
Ann Hum Genet
; 83(5): 361-366, 2019 09.
Article
em En
| MEDLINE
| ID: mdl-30977917
ABSTRACT
Four affected individuals of consanguineous kindred presented at infancy with an apparently autosomal recessive syndrome of polyuria and hypokalemic metabolic alkalosis, following maternal polyhydramnios and premature delivery, culminating in severe failure to thrive. Hypercalciuria, nephrocalcinosis, and hyperaldosteronism were further apparent as well as an unusual finding of intermittent hypernatremia. Additionally, all patients demonstrated variable micrognathia with upper respiratory airway abnormalities. As neither postnatal hyperkalemia nor permanent hearing deficits were shown, clinical assessment was consistent with antenatal Bartter syndrome (ABS) type I, which was never described before in the Israeli Bedouin population. Through genome-wide linkage analysis, we identified a single â¼3.3 Mbp disease-associated locus on chromosome 15q21.1, segregating within the pedigree. Whole-exome sequencing revealed a single novel homozygous missense mutation within this locus, in SLC12A1, encoding the Na-K-Cl cotransporter, NKCC2, in accordance with the clinical diagnosis. In this concise study, we report a novel missense mutation within the SLC12A1 gene, causing a severe form of ABS type I, the first to be described in Israeli Bedouins, with unusual clinical features of hypernatremia caused by nephrogenic diabetes insipidus and putatively related micrognathia with upper airway abnormalities .
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Síndrome de Bartter
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Árabes
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Mutação de Sentido Incorreto
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Membro 1 da Família 12 de Carreador de Soluto
Tipo de estudo:
Prognostic_studies
Limite:
Female
/
Humans
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Male
/
Newborn
País/Região como assunto:
Asia
Idioma:
En
Revista:
Ann Hum Genet
Ano de publicação:
2019
Tipo de documento:
Article
País de afiliação:
Israel