title: Coffin-Siris Syndrome with obesity, macrocephaly, hepatomegaly and hyperinsulinism caused by a mutation in the ARID1B gene.
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.
authors.affiliation: 1] Department of Paediatrics, University of Tartu, Tartu, Estonia [2] Children's Clinic, Tartu University Hospital, Tartu, Estonia [3] United Laboratories, Department of Genetics, Tartu University Hospital, Tartu, Estonia.
authors.forename: Mari-Anne
authors.initials: MA
authors.lastname: Vals
authors.affiliation: 1] Department of Paediatrics, University of Tartu, Tartu, Estonia [2] Children's Clinic, Tartu University Hospital, Tartu, Estonia.
authors.forename: Eve
authors.initials: E
authors.lastname: Õiglane-Shlik
authors.affiliation: 1] Estonian Genome Center, University of Tartu, Tartu, Estonia [2] Institute of Molecular and Cell Biology, University of Tartu, Tartu, Estonia.
authors.forename: Margit
authors.initials: M
authors.lastname: Nõukas
authors.affiliation: Tallinn Children's Hospital, Tallinn, Estonia.
authors.forename: Riina
authors.initials: R
authors.lastname: Shor
authors.affiliation: 1] Department of Paediatrics, University of Tartu, Tartu, Estonia [2] Children's Clinic, Tartu University Hospital, Tartu, Estonia.
authors.forename: Aleksandr
authors.initials: A
authors.lastname: Peet
authors.affiliation: Estonian Genome Center, University of Tartu, Tartu, Estonia.
authors.forename: Mart
authors.initials: M
authors.lastname: Kals
authors.affiliation: Estonian Genome Center, University of Tartu, Tartu, Estonia.
authors.forename: Paula Ann
authors.initials: PA
authors.lastname: Kivistik
authors.affiliation: 1] Estonian Genome Center, University of Tartu, Tartu, Estonia [2] Institute of Molecular and Cell Biology, University of Tartu, Tartu, Estonia.
authors.forename: Andres
authors.initials: A
authors.lastname: Metspalu
authors.affiliation: 1] Department of Paediatrics, University of Tartu, Tartu, Estonia [2] United Laboratories, Department of Genetics, Tartu University Hospital, Tartu, Estonia.
authors.forename: Katrin
authors.initials: K
authors.lastname: Õunap
mesh_terms: D000015:Abnormalities, Multiple / Q000235:genetics*; D000293:Adolescent; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D005145:Face / Q000002:abnormalities*; D005260:Female; D016368:Frameshift Mutation; D006228:Hand Deformities, Congenital / Q000235:genetics*; D006529:Hepatomegaly / Q000235:genetics; D006579:Heterozygote; D006801:Humans; D006946:Hyperinsulinism / Q000235:genetics; D008607:Intellectual Disability / Q000235:genetics*; D058627:Megalencephaly / Q000235:genetics; D008844:Micrognathism / Q000235:genetics*; D009333:Neck / Q000002:abnormalities*; D009765:Obesity / Q000235:genetics; D011085:Polycystic Ovary Syndrome / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism
chemical_list: C497837:ARID1B protein, human; D004268:DNA-Binding Proteins; D014157:Transcription Factors