Exome sequencing identifies a de novo FOXA2 variant in a patient with syndromic diabetes.
Pediatr Diabetes
; 20(3): 366-369, 2019 05.
Article
em En
| MEDLINE
| ID: mdl-30684292
ABSTRACT
OBJECTIVE:
When diabetes is associated with congenital malformations, without autoimmune antibodies, a genetic cause is suspected. Here, we aimed to identify a defective gene that led to diabetes. RESEARCH DESIGN ANDMETHODS:
We performed an exome analysis of an index case and his healthy parents.RESULTS:
The child presented with childhood-onset diabetes, congenital hypopituitarism, cardiac malformation, and anal atresia. A DNA analysis revealed a heterozygous de novo pathogenic variant in the developmental transcription factor, forkhead box A2 (FOXA2). The mutation resided in the DNA-binding domain, which is highly conserved among species. Tridimensional molecular dynamics simulation modeling predicted an altered interaction between the mutated protein and DNA.CONCLUSIONS:
A defect in the FOXA2 DNA-binding domain was associated with childhood-onset diabetes and multiple congenital anomalies, which reflected the pleiotropic nature of the gene. This report extends the recently described phenotype of neonatal hypoglycemia to later-onset diabetes. We suggest to include FOXA2 analysis for neonatal hypoglycemia and to implement a long-term follow-up, particularly for the risk of diabetes.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Mutação de Sentido Incorreto
/
Diabetes Mellitus
/
Fator 3-beta Nuclear de Hepatócito
Tipo de estudo:
Prognostic_studies
Limite:
Child
/
Humans
/
Male
Idioma:
En
Revista:
Pediatr Diabetes
Assunto da revista:
ENDOCRINOLOGIA
Ano de publicação:
2019
Tipo de documento:
Article
País de afiliação:
Suíça