title: A novel X-linked recessive mental retardation syndrome comprising macrocephaly and ciliary dysfunction is allelic to oral-facial-digital type I syndrome.
abstract: We report on a large family in which a novel X-linked recessive mental retardation (XLMR) syndrome comprising macrocephaly and ciliary dysfunction co-segregates with a frameshift mutation in the OFD1 gene. Mutations of OFD1 have been associated with oral-facial-digital type 1 syndrome (OFD1S) that is characterized by X-chromosomal dominant inheritance and lethality in males. In contrast, the carrier females of our family were clinically inconspicuous, and the affected males suffered from severe mental retardation, recurrent respiratory tract infections and macrocephaly. All but one of the affected males died from respiratory problems in infancy; and impaired ciliary motility was confirmed in the index patient by high-speed video microscopy examination of nasal epithelium. This family broadens the phenotypic spectrum of OFD1 mutations in an unexpected way and sheds light on the complexity of the underlying disease mechanisms.
authors.affiliation: Max Planck Institute for Molecular Genetics, Ihnestr. 73, 14195, Berlin, Germany.
authors.forename: Bartlomiej
authors.initials: B
authors.lastname: Budny
authors.forename: Wei
authors.initials: W
authors.lastname: Chen
authors.forename: Heymut
authors.initials: H
authors.lastname: Omran
authors.forename: Manfred
authors.initials: M
authors.lastname: Fliegauf
authors.forename: Andreas
authors.initials: A
authors.lastname: Tzschach
authors.forename: Marzena
authors.initials: M
authors.lastname: Wisniewska
authors.forename: Lars R
authors.initials: LR
authors.lastname: Jensen
authors.forename: Martine
authors.initials: M
authors.lastname: Raynaud
authors.forename: Sarah A
authors.initials: SA
authors.lastname: Shoichet
authors.forename: Magda
authors.initials: M
authors.lastname: Badura
authors.forename: Steffen
authors.initials: S
authors.lastname: Lenzner
authors.forename: Anna
authors.initials: A
authors.lastname: Latos-Bielenska
authors.forename: Hans-Hilger
authors.initials: HH
authors.lastname: Ropers
mesh_terms: D000483:Alleles; D015152:Blotting, Northern; D002648:Child; D002874:Chromosome Mapping; D002925:Ciliary Motility Disorders / Q000235:genetics* / Q000473:pathology; D019465:Craniofacial Abnormalities / Q000235:genetics* / Q000473:pathology; D018076:DNA, Complementary; D005260:Female; D016368:Frameshift Mutation; D005808:Genes, Recessive; D006579:Heterozygote; D006801:Humans; D008297:Male; D038901:X-Linked Intellectual Disability / Q000235:genetics* / Q000473:pathology; D010375:Pedigree; D011506:Proteins / Q000235:genetics*; D013577:Syndrome
chemical_list: D018076:DNA, Complementary; C115130:OFD1 protein, human; D011506:Proteins