Homozygous HOXA1 mutations disrupt human brainstem, inner ear, cardiovascular and cognitive development.
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.
Tischfield
Max A
MA
Department of Medicine, Program in Genomics, Children's Hospital Boston, Boston, Massachusetts 02115, USA.
Bosley
Thomas M
TM
Salih
Mustafa A M
MA
Alorainy
Ibrahim A
IA
Sener
Emin C
EC
Nester
Michael J
MJ
Oystreck
Darren T
DT
Chan
Wai-Man
WM
Andrews
Caroline
C
Erickson
Robert P
RP
Engle
Elizabeth C
EC
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
D018398:Homeodomain Proteins; D014157:Transcription Factors; D000099261:Homeobox A1 Protein