title: Homozygous HOXA1 mutations disrupt human brainstem, inner ear, cardiovascular and cognitive development.
abstract: We identified homozygous truncating mutations in HOXA1 in three genetically isolated human populations. The resulting phenotype includes horizontal gaze abnormalities, deafness, facial weakness, hypoventilation, vascular malformations of the internal carotid arteries and cardiac outflow tract, mental retardation and autism spectrum disorder. This is the first report to our knowledge of viable homozygous truncating mutations in any human HOX gene and of a mendelian disorder resulting from mutations in a human HOX gene critical for development of the central nervous system.
authors.affiliation: Department of Medicine, Program in Genomics, Children's Hospital Boston, Boston, Massachusetts 02115, USA.
authors.forename: Max A
authors.initials: MA
authors.lastname: Tischfield
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Bosley
authors.forename: Mustafa A M
authors.initials: MA
authors.lastname: Salih
authors.forename: Ibrahim A
authors.initials: IA
authors.lastname: Alorainy
authors.forename: Emin C
authors.initials: EC
authors.lastname: Sener
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Nester
authors.forename: Darren T
authors.initials: DT
authors.lastname: Oystreck
authors.forename: Wai-Man
authors.initials: WM
authors.lastname: Chan
authors.forename: Caroline
authors.initials: C
authors.lastname: Andrews
authors.forename: Robert P
authors.initials: RP
authors.lastname: Erickson
authors.forename: Elizabeth C
authors.initials: EC
authors.lastname: Engle
mesh_terms: D001321:Autistic Disorder / Q000208:ethnology / Q000235:genetics*; D001933:Brain Stem / Q000254:growth & development*; D018376:Cardiovascular Abnormalities / Q000208:ethnology / Q000235:genetics*; D002343:Carotid Artery, Internal / Q000002:abnormalities / Q000254:growth & development; D003072:Cognition Disorders / Q000235:genetics; D003638:Deafness / Q000208:ethnology / Q000235:genetics*; D007758:Ear, Inner / Q000254:growth & development; D018398:Homeodomain Proteins / Q000235:genetics*; D006720:Homozygote; D006801:Humans; D008607:Intellectual Disability / Q000208:ethnology / Q000235:genetics*; D015835:Ocular Motility Disorders / Q000208:ethnology / Q000235:genetics*; D012529:Saudi Arabia; D013577:Syndrome; D014157:Transcription Factors / Q000235:genetics*; D014421:Turkey; D000099261:Homeobox A1 Protein
chemical_list: D018398:Homeodomain Proteins; D014157:Transcription Factors; D000099261:Homeobox A1 Protein