title: Dysmorphic Features, Frontal Cerebral Cavernoma, and Hyperglycemia in a Girl with a De Novo Deletion of 7.23 Mb in Region 7p13-p12.1.
abstract: We describe the case of a 7-year-old girl referred to our diabetes unit for hyperglycemia associated with facial dysmorphic features, intellectual disability, and cerebral cavernomas. Based on presence of anti islet antigen-2 (IA2) antibodies and a human leukocyte antigen of DR3/DR4/DQ2, the patient was initially diagnosed to be a case of type 1 diabetes mellitus. At follow-up, the very good metabolic control on a low insulin dose and negative IA2 antibodies led to a suspicion of glucokinase (GCK)-related maturity-onset diabetes of the young (MODY 2). This suspicion was substantiated in multiplex ligation-dependent probe amplification (MLPA) which showed a heterozygous GCK deletion (exons 1 to 12). However, the patient's parents did not have such a deletion and were clinically euglycemic. Given the clinical picture and the MLPA findings, array based comparative genomic hybridization was performed showing a monoallelic deletion of 7.23 Mb in the short arm of chromosome 7 (7p13-p12.1). The deleted intervals contain 39 genes listed in the Online Mendelian Inheritance in Man list, including GCK associated with MODY 2, CCM2 associated with type 2 cerebral cavernous malformations, IGFBP-3 associated with decrease in postnatal growth, and OGD associated with alpha-ketoglutarate dehydrogenase deficiency, with cognitive impairment and movement abnormalities. This previously unreported deletion was considered to explain the clinical picture of the patient. Also, the findings suggest that 7p13-p12.1 contains genes involved in intellectual disability and craniofacial development.
authors.affiliation: Ramón y Cajal University Hospital, Department of Pediatrics, Pediatric Endocrinology and Diabetes Unit, Madrid, Spain.
authors.forename: Gilberto Pérez
authors.initials: GP
authors.lastname: López
authors.affiliation: Ramón y Cajal University Hospital, Department of Pediatrics, Pediatric Endocrinology and Diabetes Unit, Madrid, Spain.
authors.forename: Beatriz Villafuerte
authors.initials: BV
authors.lastname: Quispe
authors.affiliation: Ramón y Cajal University Hospital, Department of Clinical Genetics, Madrid, Spain.
authors.forename: María José
authors.initials: MJ
authors.lastname: Cabrejas Núñez
authors.affiliation: Cruces University Hospital, Research Unit, Bilbao, Spain.
authors.forename: Luis
authors.initials: L
authors.lastname: Castaño
authors.affiliation: Ramón y Cajal University Hospital, Department of Pediatrics, Pediatric Endocrinology and Diabetes Unit, Madrid, Spain.
authors.forename: Raquel
authors.initials: R
authors.lastname: Barrio
mesh_terms: D002648:Child; D002872:Chromosome Deletion; D002897:Chromosomes, Human, Pair 7; D019465:Craniofacial Abnormalities / Q000150:complications / Q000235:genetics*; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000235:genetics; D005260:Female; D006801:Humans; D006943:Hyperglycemia / Q000150:complications / Q000235:genetics*; D008607:Intellectual Disability / Q000150:complications / Q000235:genetics*; D008844:Micrognathism / Q000150:complications / Q000235:genetics*; D012272:Ribs / Q000002:abnormalities*
keywords: Glucokinase; cerebral cavernous malformation; hyperglycemia intellectual disability.; maturity-onset diabetes; oxoglutarate dehydrogenase