title: Truncation of the Down syndrome candidate gene DYRK1A in two unrelated patients with microcephaly.
abstract: We have identified and characterized two unrelated patients with prenatal onset of microcephaly, intrauterine growth retardation, feeding problems, developmental delay, and febrile seizures/epilepsy who both carry a de novo balanced translocation that truncates the DYRK1A gene at chromosome 21q22.2. DYRK1A belongs to the dual-specificity tyrosine phosphorylation-regulated kinase (DYRK) family, which is highly conserved throughout evolution. Given its localization in both the Down syndrome critical region and in the minimal region for partial monosomy 21, the gene has been studied intensively in animals and in humans, and DYRK1A has been proposed to be involved in the neurodevelopmental alterations associated with these syndromes. In the present study, we show that truncating mutations of DYRK1A result in a clinical phenotype including microcephaly.
authors.affiliation: Wilhelm Johannsen Centre for Functional Genome Research, Institute of Cellular and Molecular Medicine, University of Copenhagen, Blegdamsvej 3, 2200 Copenhagen N, Denmark.
authors.forename: Rikke S
authors.initials: RS
authors.lastname: Møller
authors.forename: Sabine
authors.initials: S
authors.lastname: Kübart
authors.forename: Maria
authors.initials: M
authors.lastname: Hoeltzenbein
authors.forename: Babett
authors.initials: B
authors.lastname: Heye
authors.forename: Ida
authors.initials: I
authors.lastname: Vogel
authors.forename: Christian P
authors.initials: CP
authors.lastname: Hansen
authors.forename: Corinna
authors.initials: C
authors.lastname: Menzel
authors.forename: Reinhard
authors.initials: R
authors.lastname: Ullmann
authors.forename: Niels
authors.initials: N
authors.lastname: Tommerup
authors.forename: Hans-Hilger
authors.initials: HH
authors.lastname: Ropers
authors.forename: Zeynep
authors.initials: Z
authors.lastname: Tümer
authors.forename: Vera M
authors.initials: VM
authors.lastname: Kalscheuer
mesh_terms: D002648:Child; D002891:Chromosomes, Human, Pair 21 / Q000235:genetics*; D004314:Down Syndrome / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D006801:Humans; D007223:Infant; D008297:Male; D008831:Microcephaly / Q000235:genetics*; D009154:Mutation; D010641:Phenotype; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D011505:Protein-Tyrosine Kinases / Q000235:genetics*; D000097603:Dyrk Kinases
chemical_list: D017346:Protein Serine-Threonine Kinases; D011505:Protein-Tyrosine Kinases; D000097603:Dyrk Kinases