title: Delineation of the KIAA2022 mutation phenotype: two patients with X-linked intellectual disability and distinctive features.
abstract: Next-generation sequencing has enabled the screening for a causative mutation in X-linked intellectual disability (XLID). We identified KIAA2022 mutations in two unrelated male patients by targeted sequencing. We selected 13 Japanese male patients with severe intellectual disability (ID), including four sibling patients and nine sporadic patients. Two of thirteen had a KIAA2022 mutation. Patient 1 was a 3-year-old boy. He had severe ID with autistic behavior and hypotonia. Patient 2 was a 5-year-old boy. He also had severe ID with autistic behavior, hypotonia, central hypothyroidism, and steroid-dependent nephrotic syndrome. Both patients revealed consistent distinctive features, including upswept hair, narrow forehead, downslanting eyebrows, wide palpebral fissures, long nose, hypoplastic alae nasi, open mouth, and large ears. De novo KIAA2022 mutations (p.Q705X in Patient 1, p.R322X in Patient 2) were detected by targeted sequencing and confirmed by Sanger sequencing. KIAA2022 mutations and alterations have been reported in only four families with nonsyndromic ID and epilepsy. KIAA2022 is highly expressed in the fetal and adult brain and plays a crucial role in neuronal development. These additional patients support the evidence that KIAA2022 is a causative gene for XLID.
authors.affiliation: Division of Medical Genetics, Kanagawa Children's Medical Center, Yokohama, Japan.
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Kuroda
authors.affiliation: Division of Medical Genetics, Kanagawa Children's Medical Center, Yokohama, Japan.
authors.forename: Ikuko
authors.initials: I
authors.lastname: Ohashi
authors.affiliation: Division of Medical Genetics, Kanagawa Children's Medical Center, Yokohama, Japan.
authors.forename: Takuya
authors.initials: T
authors.lastname: Naruto
authors.affiliation: Division of Medical Genetics, Kanagawa Children's Medical Center, Yokohama, Japan.
authors.forename: Kazumi
authors.initials: K
authors.lastname: Ida
authors.affiliation: Division of Medical Genetics, Kanagawa Children's Medical Center, Yokohama, Japan.
authors.forename: Yumi
authors.initials: Y
authors.lastname: Enomoto
authors.affiliation: Department of Clinical Laboratory, Kanagawa Children's Medical Center, Yokohama, Japan.
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Saito
authors.affiliation: Department of Clinical Laboratory, Kanagawa Children's Medical Center, Yokohama, Japan.
authors.forename: Jun-Ichi
authors.initials: J
authors.lastname: Nagai
authors.affiliation: Division of Pediatric Neurology, Kanagawa Children's Medical Center, Yokohama, Japan.
authors.forename: Takahito
authors.initials: T
authors.lastname: Wada
authors.affiliation: Division of Medical Genetics, Kanagawa Children's Medical Center, Yokohama, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Kurosawa
mesh_terms: D000483:Alleles; D001321:Autistic Disorder / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D002675:Child, Preschool; D003409:Congenital Hypothyroidism / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D015870:Gene Expression; D050172:Genes, X-Linked; D006579:Heterozygote; D059014:High-Throughput Nucleotide Sequencing; D006720:Homozygote; D006801:Humans; D008607:Intellectual Disability / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D008297:Male; D009123:Muscle Hypotonia / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D020125:Mutation, Missense; D009419:Nerve Tissue Proteins / Q000235:genetics*; D010375:Pedigree; D010641:Phenotype
chemical_list: C000598871:NEXMIF protein, human; D009419:Nerve Tissue Proteins
keywords: KIAA2022; X-linked intellectual disability; next-generation sequencing; targeted sequencing