ABSTRACT
Coffin-Siris Syndrome (CSS, MIM 135900) is a rare genetic disorder, and mutations in ARID1B were recently shown to cause CSS. In this study, we report a novel ARID1B mutation identified by whole-exome sequencing in a patient with clinical features of CSS. We identified a novel heterozygous frameshift mutation c.1584delG in exon 2 of ARID1B (NM_020732.3) predicting a premature stop codon p.(Leu528Phefs*65). Sanger sequencing confirmed the c.1584delG mutation as a de novo in the proband and that it was not present either in her parents, half-sister or half-brother. Clinically, the patient presented with extreme obesity, macrocephaly, hepatomegaly, hyperinsulinism and polycystic ovarian syndrome (PCOS), which have previously not been described in CSS patients. We suggest that obesity, macrocephaly, hepatomegaly and/or PCOS may be added to the list of clinical features of ARID1B mutations, but further clinical reports are required to make a definite conclusion.
Subject(s)
Abnormalities, Multiple/genetics , DNA-Binding Proteins/genetics , Face/abnormalities , Hand Deformities, Congenital/genetics , Intellectual Disability/genetics , Micrognathism/genetics , Neck/abnormalities , Transcription Factors/genetics , Adolescent , DNA-Binding Proteins/metabolism , Female , Frameshift Mutation , Hepatomegaly/genetics , Heterozygote , Humans , Hyperinsulinism/genetics , Megalencephaly/genetics , Obesity/genetics , Polycystic Ovary Syndrome/genetics , Transcription Factors/metabolismABSTRACT
BACKGROUND: We aimed to determine the prevalence and characteristics of celiac disease in children with type 1 diabetes in Estonia, a country with a formerly low frequency of both diseases. METHODS: Altogether, 271 patients with diabetes were studied over 12 years (1995-2006): 122 at diagnosis and 149 patients 0.1-14.8 years after diagnosis. In addition, 73 patients were followed up over 1-6 years. Immunoglobulin A type endomysium and tissue transglutaminase antibodies were determined. Patients with antibodies and/or with celiac-disease-related symptoms were invited for a small-intestinal biopsy. RESULTS: At the primary screening, celiac disease was histologically confirmed in nine patients (all without symptoms), that is, in 3.3% (95% confidence interval: 1.63-6.42) of type 1 diabetes cases. At follow up, celiac disease was additionally detected in two (2.7%) of 73 diabetic patients, that is, in 0.016 (95% confidence interval: 0-0.072) celiac disease cases per follow-up year. CONCLUSION: The prevalence of celiac disease among type 1 diabetes patients in Estonia is similar to that in countries with a high incidence of celiac disease and type 1 diabetes. As celiac disease is mostly symptomless, all children with type 1 diabetes, irrespective of their geographic origin, should be regularly screened for celiac disease.