Permanent neonatal diabetes caused by dominant, recessive, or compound heterozygous SUR1 mutations with opposite functional effects.
Am J Hum Genet
; 81(2): 375-82, 2007 Aug.
Article
en En
| MEDLINE
| ID: mdl-17668386
ABSTRACT
Heterozygous activating mutations in the KCNJ11 gene encoding the pore-forming Kir6.2 subunit of the pancreatic beta cell K(ATP) channel are the most common cause of permanent neonatal diabetes (PNDM). Patients with PNDM due to a heterozygous activating mutation in the ABCC8 gene encoding the SUR1 regulatory subunit of the K(ATP) channel have recently been reported. We studied a cohort of 59 patients with permanent diabetes who received a diagnosis before 6 mo of age and who did not have a KCNJ11 mutation. ABCC8 gene mutations were identified in 16 of 59 patients and included 8 patients with heterozygous de novo mutations. A recessive mode of inheritance was observed in eight patients with homozygous, mosaic, or compound heterozygous mutations. Functional studies of selected mutations showed a reduced response to ATP consistent with an activating mutation that results in reduced insulin secretion. A novel mutational mechanism was observed in which a heterozygous activating mutation resulted in PNDM only when a second, loss-of-function mutation was also present.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Receptores de Droga
/
Canales de Potasio
/
Transportadoras de Casetes de Unión a ATP
/
Canales de Potasio de Rectificación Interna
/
Diabetes Mellitus
/
Mutación
Tipo de estudio:
Etiology_studies
/
Incidence_studies
/
Observational_studies
/
Prognostic_studies
/
Risk_factors_studies
Límite:
Humans
/
Newborn
Idioma:
En
Año:
2007
Tipo del documento:
Article