title: A syndrome of microcephaly, short stature, polysyndactyly, and dental anomalies caused by a homozygous KATNB1 mutation.
abstract: Using whole-exome sequencing, we identified a homozygous acceptor splice-site mutation in intron 6 of the KATNB1 gene in a patient from a consanguineous Turkish family who presented with congenital microcephaly, lissencephaly, short stature, polysyndactyly, and dental abnormalities. cDNA analysis revealed complete loss of the natural acceptor splice-site resulting either in the usage of an alternative, exonic acceptor splice-site inducing a frame-shift and premature protein truncation or, to a minor extent, in complete skipping of exon 7. Both effects most likely lead to complete loss of KATNB1 function. Homozygous and compound heterozygous mutations in KATNB1 have very recently been described as a cause of microcephaly with brain malformations and seizures. We extend the KATNB1 associated phenotype by describing a syndrome characterized by primordial dwarfism, lissencephaly, polysyndactyly, and dental anomalies, which is caused by a homozygous truncating KATNB1 mutation.
authors.affiliation: Institute of Human Genetics, University of Cologne, Cologne, Germany.|Center for Molecular Medicine Cologne (CMMC), University of Cologne, Cologne, Germany.|Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, Cologne, Germany.
authors.forename: Gökhan
authors.initials: G
authors.lastname: Yigit
authors.affiliation: Institut für Humangenetik, Universitätsklinikum Essen, Universität Duisburg-Essen, Essen, Germany.
authors.forename: Dagmar
authors.initials: D
authors.lastname: Wieczorek
authors.affiliation: Institute of Human Genetics, University of Cologne, Cologne, Germany.|Center for Molecular Medicine Cologne (CMMC), University of Cologne, Cologne, Germany.|Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, Cologne, Germany.
authors.forename: Nina
authors.initials: N
authors.lastname: Bögershausen
authors.affiliation: Institute of Human Genetics, University of Cologne, Cologne, Germany.|Center for Molecular Medicine Cologne (CMMC), University of Cologne, Cologne, Germany.|Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, Cologne, Germany.
authors.forename: Filippo
authors.initials: F
authors.lastname: Beleggia
authors.affiliation: Department of Neuroradiology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.
authors.forename: Claudia
authors.initials: C
authors.lastname: Möller-Hartmann
authors.affiliation: Institute of Human Genetics, University of Cologne, Cologne, Germany.|Cologne Center for Genomics (CCG), University of Cologne, Cologne, Germany.
authors.forename: Janine
authors.initials: J
authors.lastname: Altmüller
authors.affiliation: Cologne Center for Genomics (CCG), University of Cologne, Cologne, Germany.
authors.forename: Holger
authors.initials: H
authors.lastname: Thiele
authors.affiliation: Center for Molecular Medicine Cologne (CMMC), University of Cologne, Cologne, Germany.|Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, Cologne, Germany.|Cologne Center for Genomics (CCG), University of Cologne, Cologne, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Nürnberg
authors.affiliation: Institute of Human Genetics, University of Cologne, Cologne, Germany.|Center for Molecular Medicine Cologne (CMMC), University of Cologne, Cologne, Germany.|Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, Cologne, Germany.|Institute of Human Genetics, University Medical Center Göttingen, Göttingen, Germany.
authors.forename: Bernd
authors.initials: B
authors.lastname: Wollnik
mesh_terms: D002675:Child, Preschool; D004252:DNA Mutational Analysis; D004392:Dwarfism / Q000175:diagnosis / Q000235:genetics*; D059472:Exome; D005260:Female; D023061:Gene Order; D056426:Genetic Loci; D059014:High-Throughput Nucleotide Sequencing; D006720:Homozygote; D006801:Humans; D054082:Lissencephaly / Q000175:diagnosis / Q000235:genetics*; D008279:Magnetic Resonance Imaging; D008831:Microcephaly / Q000175:diagnosis / Q000235:genetics*; D009154:Mutation; D010375:Pedigree; D010641:Phenotype; D013576:Syndactyly / Q000175:diagnosis / Q000235:genetics*; D013577:Syndrome
keywords: KATNB1; katanin; lissencephaly; microcephalic primordial dwarfism; polydactyly