title: Novel de novo mutations in ZBTB20 in Primrose syndrome with congenital hypothyroidism.
abstract: The cardinal features of Primrose syndrome (MIM 259050) are dysmorphic facial features, macrocephaly, and intellectual disability, as well as large body size, height and weight, and calcified pinnae. A variety of neurological signs and symptoms have been reported including hearing loss, autism, behavioral abormalities, hypotonia, cerebral calcifications, and hypoplasia of the corpus callosum. Recently, heterozygous de novo missense mutations in ZBTB20, coding for a zing finger protein, have been identified in Primrose syndrome patients. We report a boy with intellectual disability carrying two de novo missense mutations in the last exon of ZBTB20 (Ser616Phe and Gly741Arg; both previously unreported). One of them, Ser616Phe, affects an amino acid located in one of the C2H2 zing-fingers involved in DNA-binding and close to other missense mutations already described. Reverse phenotyping showed that this patient presents with classic features of Primrose syndrome (dysmorphic facies, macrocephaly, hearing loss, hypotonia, hypoplasia of the corpus callosum) and, in addition, congenital hypothyroidism. Review of the literature reveals another Primrose syndrome patient with hypothyroidism and thus, this may represent an under recognized component that should be investigated in other patients. © 2016 Wiley Periodicals, Inc.
authors.affiliation: Department of Translational Medicine and Neurogenetics, IGBMC, Illkirch, France.
authors.forename: Francesca
authors.initials: F
authors.lastname: Mattioli
authors.affiliation: Department of Translational Medicine and Neurogenetics, IGBMC, Illkirch, France.|Laboratoire de Diagnostic Génétique, Hôpitaux Universitaires de Strasbourg, Strasbourg, France.
authors.forename: Amelie
authors.initials: A
authors.lastname: Piton
authors.affiliation: Laboratoire de Diagnostic Génétique, Hôpitaux Universitaires de Strasbourg, Strasbourg, France.
authors.forename: Bénédicte
authors.initials: B
authors.lastname: Gérard
authors.affiliation: Centre for Molecular Diseases and Department of Pediatrics, Lausanne University Hospital (CHUV), University of Lausanne, Lausanne, Switzerland.
authors.forename: Andrea
authors.initials: A
authors.lastname: Superti-Furga
authors.affiliation: Department of Translational Medicine and Neurogenetics, IGBMC, Illkirch, France.|Laboratoire de Diagnostic Génétique, Hôpitaux Universitaires de Strasbourg, Strasbourg, France.|Chaire de Génétique Humaine, Collège de France, Paris, France.
authors.forename: Jean-Louis
authors.initials: JL
authors.lastname: Mandel
authors.affiliation: Service of Medical Genetics, Lausanne University Hospital (CHUV), Lausanne, Switzerland.
authors.forename: Sheila
authors.initials: S
authors.lastname: Unger
mesh_terms: D000015:Abnormalities, Multiple / Q000175:diagnosis* / Q000235:genetics*; D015415:Biomarkers; D002114:Calcinosis / Q000175:diagnosis* / Q000235:genetics*; D055028:Comparative Genomic Hybridization; D003409:Congenital Hypothyroidism / Q000175:diagnosis* / Q000235:genetics*; D004427:Ear Diseases / Q000175:diagnosis* / Q000235:genetics*; D019066:Facies; D056726:Genetic Association Studies; D006801:Humans; D007223:Infant; D008607:Intellectual Disability / Q000175:diagnosis* / Q000235:genetics*; D008297:Male; D009133:Muscular Atrophy / Q000175:diagnosis* / Q000235:genetics*; D009154:Mutation; D020125:Mutation, Missense; D009419:Nerve Tissue Proteins / Q000235:genetics*; D010375:Pedigree; D010641:Phenotype; D014157:Transcription Factors / Q000235:genetics*
chemical_list: D015415:Biomarkers; D009419:Nerve Tissue Proteins; D014157:Transcription Factors; C427486:ZBTB20 protein, human
keywords: Primrose syndrome; ZBTB20; congenital hypothyroidism; macrocephaly