title: TBCK-related intellectual disability syndrome: Case study of two patients.
abstract: There is a significant level of genetic heterogeneity underlying the phenotype of nonspecific hypotonia with severe intellectual disability. Exome sequencing has proven to be a powerful tool for identifying the underlying molecular basis of such nonspecific, abnormal neurological phenotypes. Mutations in the TBCK gene have been reported associated with very poor, if any, psychomotor development, poor speech, and inability to walk independently. We describe the long-term phenotypic evolution of a severe nonspecific neurodevelopmental disorder in two siblings born to an Arab-Moslem family living in northern Israel. Exome sequencing led to identification of a novel homozygous mutation: c.1854delT in the TBCK gene. Abnormal elevated β-HCG was found in the maternal serum during the two pregnancies, a finding that has not been reported before. These individuals present with severe intellectual disability, no speech, hypotonia, convulsions, and lack of any independent daily skills. © 2016 Wiley Periodicals, Inc.
authors.affiliation: Rambam Health Care Campus, Metabolic Unit, Rappaport School of Medicine, Technion-Israel Institute of Technology, Haifa, Israel.
authors.forename: Hanna
authors.initials: H
authors.lastname: Mandel
authors.affiliation: Genetics Institute, Ha'emek Medical Center, Afula, Israel.
authors.forename: Morad
authors.initials: M
authors.lastname: Khayat
authors.affiliation: Genetics Institute, Ha'emek Medical Center, Afula, Israel.
authors.forename: Elana
authors.initials: E
authors.lastname: Chervinsky
authors.affiliation: The Monique and Jacques Roboh Department of Genetic Research, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.
authors.forename: Orly
authors.initials: O
authors.lastname: Elpeleg
authors.affiliation: Genetics Institute, Ha'emek Medical Center, Afula, Israel.|Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel.
authors.forename: Stavit
authors.initials: S
authors.lastname: Shalev
mesh_terms: D001921:Brain / Q000002:abnormalities; D059472:Exome; D056726:Genetic Association Studies; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D007231:Infant, Newborn; D008607:Intellectual Disability / Q000175:diagnosis* / Q000235:genetics*; D008279:Magnetic Resonance Imaging; D008297:Male; D009154:Mutation; D010375:Pedigree; D010641:Phenotype; D010808:Physical Examination; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D013577:Syndrome; D014057:Tomography, X-Ray Computed; D014463:Ultrasonography
chemical_list: D017346:Protein Serine-Threonine Kinases; C587598:TBCK protein, human
keywords: TBCK; exome sequencing; neurodevelopmental disorder