HOXA1 and the Bosley–Salih–Alorainy and Athabascan Brainstem Dysgenesis Syndromes

Abstract

Abstract Homeobox A1 (HOXA1), the 3′ most member in the HOXA gene cluster, encodes a transcription factor that is necessary for catalyzing gene expression pathways important for rostral development of the vertebrate embryo. Two syndromes resulting from homozygous HOXA1 mutations, Bosley–Salih–Alorainy syndrome (BSAS) and Athabascan brain stem dysgenesis syndrome (ABDS), have been discovered in patients from three genetically isolated populations in the Middle East and American southwest. Affected individuals have a pleiotropic spectrum of phenotypes including horizontal gaze abnormalities, facial weakness, deafness, hypoventilation, skull deformities, autism, mental retardation, internal carotid artery (ICA) malformations, and conotruncal heart defects (TischFeld et al., 2005). Although horizontal gaze abnormalities and sensorineural deafness are the most penetrant aspects of the syndrome, the remaining phenotypes demonstrate variable expressivity that may be dependent upon genetic background.