Genetic basis of early-onset, maturity-onset diabetes of the young-like diabetes in Japan and features of patients without mutations in the major MODY genes: Dominance of maternal inheritance.
Pediatr Diabetes
; 19(7): 1164-1172, 2018 11.
Article
em En
| MEDLINE
| ID: mdl-29927023
ABSTRACT
BACKGROUND:
Causative mutations cannot be identified in the majority of Asian patients with suspected maturity-onset diabetes of the young (MODY).OBJECTIVES:
To elucidate the genetic basis of Japanese patients with MODY-like diabetes and gain insight into the etiology of patients without mutations in the major MODY genes.SUBJECTS:
A total of 263 Japanese patients with early-onset, non-obese, MODY-like diabetes mellitus referred to Osaka City General Hospital for diagnosis.METHODS:
Mutational analysis of the four major MODY genes (GCK, HNF1A, HNF4A, HNF1B) by Sanger sequencing. Mutation-positive and mutation-negative patients were further analyzed for clinical features.RESULTS:
Mutations were identified in 103 (39.2%) patients; 57 mutations in GCK; 29, HNF1A; 7, HNF4A; and 10, HNF1B. Contrary to conventional diagnostic criteria, 18.4% of mutation-positive patients did not have affected parents and 8.2% were in the overweight range (body mass index [BMI] >85th percentile). HOMA-IR at diagnosis was elevated (>2) in 15 of 66 (22.7%) mutation-positive patients. Compared with mutation-positive patients, mutation-negative patients were significantly older (P = 0.003), and had higher BMI percentile at diagnosis (P = 0.0006). Interestingly, maternal inheritance of diabetes was significantly more common in mutation-negative patients (P = 0.0332) and these patients had significantly higher BMI percentile as compared with mutation-negative patients with paternal inheritance (P = 0.0106).CONCLUSIONS:
Contrary to the conventional diagnostic criteria, de novo diabetes, overweight, and insulin-resistance are common in Japanese patients with mutation-positive MODY. A significant fraction of mutation-negative patients had features of early-onset type 2 diabetes common in Japanese, and non-Mendelian inheritance needs to be considered for these patients.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Proteínas Serina-Treonina Quinases
/
Diabetes Mellitus Tipo 2
/
Fatores Nucleares de Hepatócito
/
Herança Materna
Tipo de estudo:
Prognostic_studies
Limite:
Adolescent
/
Adult
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Child
/
Child, preschool
/
Female
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Humans
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Male
País/Região como assunto:
Asia
Idioma:
En
Revista:
Pediatr Diabetes
Assunto da revista:
ENDOCRINOLOGIA
Ano de publicação:
2018
Tipo de documento:
Article
País de afiliação:
Japão