RESUMEN
Neonatal diabetes is a highly genetically heterogeneous disorder. There are over 20 distinct syndromic and non-syndromic forms, including dominant, recessive and X-linked subtypes. Biallelic truncating or mis-sense mutations in the DNA-binding domain of the RFX6 transcription factor cause an autosomal recessive, syndromic form of neonatal diabetes previously described as Mitchell-Riley syndrome. In all, eight cases have been reported, with the age at onset of diabetes in the first 2 weeks of life. Here we report two individuals born to double first cousins in whom intestinal atresias consistent with a diagnosis of Mitchell-Riley syndrome were diagnosed at birth, but in whom diabetes did not present until the ages of 3 and 6 years. Novel compound heterozygous RFX6 nonsense mutations (p.Arg726X/p.Arg866X) were identified at the 3' end of the gene. The later onset of diabetes in these patients may be due to incomplete inactivation of RFX6. Genetic testing for RFX6 mutations should be considered in patients presenting with intestinal atresias in the absence of neonatal diabetes.
Asunto(s)
Codón sin Sentido , Proteínas de Unión al ADN/genética , Diabetes Mellitus/genética , Enfermedades de la Vesícula Biliar/genética , Atresia Intestinal/genética , Factores de Transcripción/genética , Adolescente , Alelos , Niño , Diabetes Mellitus/diagnóstico , Femenino , Enfermedades de la Vesícula Biliar/diagnóstico , Heterocigoto , Humanos , Atresia Intestinal/diagnóstico , Masculino , Factores de Transcripción del Factor Regulador XRESUMEN
The ileal bile acid-binding protein (IBABP) is important for the reabsorption of bile salts in the distal small intestine. Studies with the human IBABP gene (FABP6, on chromosome 5q33.3-q34) defined the major transcription start site and identified conserved elements. A consensus element for the caudal-related homeobox factor CDX2 was functional in gel-shift assays and in transfection experiments.