title: Novel homozygous mutation in KPTN gene causing a familial intellectual disability-macrocephaly syndrome.
abstract: Recently, a novel autosomal recessive developmental delay-macrocephaly syndrome was described caused by homozygous or compound heterozygous mutations in the KPTN gene. All reported patients belonged to one large Amish kindred. We report on the second case of KPTN-related syndrome in two Estonian adult sibs. The brother and sister both have macrocephaly and moderate intellectual disability, and their verbal abilities are more affected than motor development. No notable minor anomalies are present. Behavioral problems and a few episodes of seizures were reported in the brother. Whole exome sequencing carried out from the brother's DNA sample identified homozygous one-nucleotide frameshift duplication c.665dupA (p.Q222fs) in the KPTN gene. Homozygosity of both affected sibs and heterozygosity of parents were confirmed by Sanger sequencing. Thus, we confirm the pathogenicity of KPTN mutations and further delineate the novel developmental delay-macrocephaly syndrome. We also support the hypothesis that KPTN-related syndrome is not restricted to the Amish population.
authors.affiliation: Department of Genetics, United Laboratories, Tartu University Hospital, Tartu, Estonia.|Institute of Biomedicine and Translational Medicine, Department of Biomedicine, University of Tartu, Tartu, Estonia.
authors.forename: Sander
authors.initials: S
authors.lastname: Pajusalu
authors.affiliation: Department of Genetics, United Laboratories, Tartu University Hospital, Tartu, Estonia.|Institute of Biomedicine and Translational Medicine, Department of Biomedicine, University of Tartu, Tartu, Estonia.|Department of Paediatrics, University of Tartu, Tartu, Estonia.
authors.forename: Tiia
authors.initials: T
authors.lastname: Reimand
authors.affiliation: Department of Genetics, United Laboratories, Tartu University Hospital, Tartu, Estonia.|Department of Paediatrics, University of Tartu, Tartu, Estonia.
authors.forename: Katrin
authors.initials: K
authors.lastname: Õunap
mesh_terms: D000328:Adult; D005260:Female; D006801:Humans; D008607:Intellectual Disability / Q000235:genetics*; D008297:Male; D058627:Megalencephaly / Q000235:genetics*; D008840:Microfilament Proteins / Q000235:genetics*; D009154:Mutation; D055815:Young Adult
chemical_list: C119742:KPTN protein, human; D008840:Microfilament Proteins
keywords: KPTN protein; homozygote; intellectual disability; megalencephaly; whole exome sequencing