HNF1B alterations associated with congenital anomalies of the kidney and urinary tract.
Pediatr Nephrol
; 25(6): 1073-9, 2010 Jun.
Article
em En
| MEDLINE
| ID: mdl-20155289
ABSTRACT
Hepatocyte nuclear factor 1beta (HNF1beta) abnormalities have been recognized to cause congenital anomalies of the kidney and urinary tract (CAKUT), predominantly affecting bilateral renal malformations. To further understand the spectrum of HNF1beta related phenotypes, we performed HNF1B gene mutation and deletion analyses in Japanese patients with renal hypodysplasia (n = 31), unilateral multicystic dysplastic kidney (MCDK; n = 14) and others (n = 5). We identified HNF1B alterations in 5 out of 50 patients (10%). De novo heterozygous complete deletions of HNF1B were found in 3 patients with unilateral MCDK. Two of the patients showed contralateral hypodysplasia, whereas the other patient showed a radiologically normal contralateral kidney with normal renal function. Copy number variation analyses showed 1.4 Mb microdeletions involving the whole HNF1B gene with breakpoints in flanking segmental duplications. We also identified 1 novel truncated mutation (1007insC) and another missense mutation (226G>T) in patients with bilateral hypodysplasia. HNF1B alterations leading to haploinsufficiency affect a diverse spectrum of CAKUT. The existence of a patient with unilateral MCDK with normal renal function might provide genetic insight into the etiology of these substantial populations of only unilateral MCDK. The recurrent microdeletions encompassing HNF1B could have a significant impact on the mechanism of HNF1B deletions.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Sistema Urinário
/
Fator 1-beta Nuclear de Hepatócito
/
Rim
/
Nefropatias
Tipo de estudo:
Prognostic_studies
/
Risk_factors_studies
Limite:
Adolescent
/
Adult
/
Child
/
Child, preschool
/
Female
/
Humans
/
Male
Idioma:
En
Revista:
Pediatr Nephrol
Assunto da revista:
NEFROLOGIA
/
PEDIATRIA
Ano de publicação:
2010
Tipo de documento:
Article
País de afiliação:
Japão