Biallelic RFX6 mutations can cause childhood as well as neonatal onset diabetes mellitus.
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.
Institute of Biomedical and Clinical Science, University of Exeter Medical School, Exeter, UK.
Francis H
FH
Sansbury
Endocrinology Unit, Faculty of Medicine, Department of Pediatrics, Eskişehir Osmangazi University, Eskişehir, Turkey.
Birgül
B
Kirel
Institute of Biomedical and Clinical Science, University of Exeter Medical School, Exeter, UK.
Richard
R
Caswell
Hana Lango
HL
Allen
Institute of Biomedical and Clinical Science, University of Exeter Medical School, Exeter, UK.
Hana
H
Lango Allen
Institute of Biomedical and Clinical Science, University of Exeter Medical School, Exeter, UK.
Sarah E
SE
Flanagan
Institute of Biomedical and Clinical Science, University of Exeter Medical School, Exeter, UK.
Andrew T
AT
Hattersley
Institute of Biomedical and Clinical Science, University of Exeter Medical School, Exeter, UK.
Sian
S
Ellard
Institute of Biomedical and Clinical Science, University of Exeter Medical School, Exeter, UK.
Charles J
CJ
Shaw-Smith
D000293:Adolescent; D000483:Alleles; D002648:Child; D018389:Codon, Nonsense; D004268:DNA-Binding Proteins / Q000235:genetics*; D003920:Diabetes Mellitus / Q000175:diagnosis / Q000235:genetics*; D005260:Female; D005705:Gallbladder Diseases / Q000175:diagnosis / Q000235:genetics*; D006579:Heterozygote; D006801:Humans; D007409:Intestinal Atresia / Q000175:diagnosis / Q000235:genetics*; D008297:Male; D000071701:Regulatory Factor X Transcription Factors; D014157:Transcription Factors / Q000235:genetics*
D018389:Codon, Nonsense; D004268:DNA-Binding Proteins; D000071701:Regulatory Factor X Transcription Factors; C547964:Rfx6 protein, human; D014157:Transcription Factors