RESUMEN
Neonatal diabetes is a rare disease, often caused by a monogenic abnormality. A male infant patient developed diabetic ketoacidosis at 2 months-of-age due to the heterozygous ABCC8 gene mutation (p.Pro1198Leu). After genetic diagnosis, insulin therapy was successfully transitioned to oral sulfonylurea therapy. For >6 years, oral sulfonylurea therapy has been safe and effective, and the required amount of sulfonylureas has progressively decreased. The mutation was transmitted in an autosomal-dominant fashion across three generations of his family, but the severity of diabetes varied among members from neonatal diabetes to mild diabetes. One family member had normal glucose tolerance despite having the mutation. This case presentation could help in the understanding of neonatal diabetes caused by the ABCC8 gene mutation.
Asunto(s)
Cetoacidosis Diabética/genética , Receptores de Sulfonilureas/genética , Cetoacidosis Diabética/tratamiento farmacológico , Gliburida/uso terapéutico , Hemoglobina Glucada/análisis , Humanos , Hipoglucemiantes/uso terapéutico , Recién Nacido , Enfermedades del Recién Nacido , Insulina/uso terapéutico , Masculino , Mutación , Linaje , Resultado del TratamientoRESUMEN
Activating mutations in the ABCC8 gene cause diabetes and inactivating mutations usually cause hyperinsulinemic hypoglycemia in infancy. Patients with hypoglycemia in infancy due to a heterozygous inactivating mutation have been reported to occasionally progress to diabetes later in life. We explored the gene responsible for diabetes in two brothers, who were suspected to have diabetes at 15 and 18 years-of-age, respectively, with whole exome sequencing, and identified a compound heterozygous ABCC8 gene mutation (p.Arg168Cys and p.Arg1421Cys). Although their father and mother were heterozygous carriers of the p.Arg168Cys and the p.Arg1421Cys mutation, respectively, neither parent had diabetes. These mutations have been reported to be responsible for hypoglycemia in infancy and function as an inactivating mutation. Our results suggest that the inactivating ABCC8 gene mutation is also important in the etiology of diabetes.
Asunto(s)
Diabetes Mellitus/genética , Receptores de Sulfonilureas/genética , Adolescente , Edad de Inicio , Hiperinsulinismo Congénito/genética , Humanos , Masculino , Mutación , Linaje , Secuenciación del ExomaAsunto(s)
Hiperinsulinismo Congénito/genética , Hiperglucemia/genética , Hipoglucemia/genética , Mutación Missense , Receptores de Sulfonilureas/genética , Adolescente , Adulto , Niño , Hiperinsulinismo Congénito/sangre , Hiperinsulinismo Congénito/diagnóstico , Diabetes Mellitus/sangre , Diabetes Mellitus/diagnóstico , Diabetes Mellitus/genética , Salud de la Familia , Femenino , Hemoglobina Glucada/análisis , Heterocigoto , Humanos , Hiperglucemia/sangre , Hiperglucemia/diagnóstico , Hipoglucemia/sangre , Hipoglucemia/diagnóstico , Masculino , Persona de Mediana Edad , LinajeRESUMEN
Whole-exome sequencing is a new technology. We used it to explore the gene responsible for early-onset diabetes as a result of impaired insulin secretion in a family. In the INS gene, we identified the heterozygous c.188-31G>A mutation in the proband - a 43-year-old woman. The mutation was also identified in her two daughters with diabetes, but not in her son or her parents, all of whom did not have diabetes. The substitution was located 31 bp proximal to exon 3 in intron 2. It was predicted to create an ectopic splice site leading to inserting 29 nucleotides of intron 2 as an exonic sequence in the transcript. The mutation has been reported in White families, and the present case is the first report in an Asian person. The present results would help in understanding the role of the mutation in developing diabetes.