Mutations in SLC12A3 and CLCNKB and Their Correlation with Clinical Phenotype in Patients with Gitelman and Gitelman-like Syndrome
Journal of Korean Medical Science
;
: 47-54, 2016.
Artigo
em Inglês
| WPRIM
| ID: wpr-28305
ABSTRACT
Gitelman's syndrome (GS) is caused by loss-of-function mutations in SLC12A3 and characterized by hypokalemic metabolic alkalosis, hypocalciuria, and hypomagnesemia. Long-term prognosis and the role of gene diagnosis in GS are still unclear. To investigate genotype-phenotype correlation in GS and Gitelman-like syndrome, we enrolled 34 patients who showed hypokalemic metabolic alkalosis without secondary causes. Mutation analysis of SLC12A3 and CLCNKB was performed. Thirty-one patients had mutations in SLC12A3, 5 patients in CLCNKB, and 2 patients in both genes. There was no significant difference between male and female in clinical manifestations at the time of presentation, except for early onset of symptoms in males and more profound hypokalemia in females. We identified 10 novel mutations in SLC12A3 and 4 in CLCNKB. Compared with those with CLCNKB mutations, patients with SLC12A3 mutations were characterized by more consistent hypocalciuria and hypomagnesemia. Patients with 2 mutant SLC12A3 alleles, compared with those with 1 mutant allele, did not have more severe clinical and laboratory findings except for lower plasma magnesium concentrations. Male and female patients did not differ in their requirement for electrolyte replacements. Two patients with concomitant SLC12A3 and CLCNKB mutations had early-onset severe symptoms and showed different response to treatment. Hypocalciuria and hypomagnesemia are useful markers in differentiation of GS and classical Bartter's syndrome. Gender, genotypes or the number of SLC12A3 mutant alleles cannot predict the severity of disease or response to treatment.
Texto completo:
DisponíveL
Índice:
WPRIM (Pacífico Ocidental)
Assunto principal:
Fenótipo
/
Polimorfismo Genético
/
Síndrome de Bartter
/
Análise Mutacional de DNA
/
Canais de Cloreto
/
Alelos
/
Síndrome de Gitelman
/
Estudos de Associação Genética
/
Membro 3 da Família 12 de Carreador de Soluto
/
Genótipo
Tipo de estudo:
Estudo prognóstico
Limite:
Adolescente
/
Adulto
/
Feminino
/
Humanos
/
Masculino
Idioma:
Inglês
Revista:
Journal of Korean Medical Science
Ano de publicação:
2016
Tipo de documento:
Artigo
Similares
MEDLINE
...
LILACS
LIS