title: HESX1: a novel gene implicated in a familial form of septo-optic dysplasia.
abstract: The homeobox gene Hesx1, which encodes a pituitary transcription factor, is first expressed at gastrulation in the mouse embryo. Hesx1 expression begins in prospective forebrain tissue but later becomes restricted to Rathke's pouch, the primordium of the anterior pituitary gland. Transgenic mice lacking Hesx1 exhibit a phenotype comprising variable anterior CNS defects, such as a reduced prosencephalon, abnormalities in the corpus callosum and septum pellucidum, anophthalmia or microphthalmia, defective olfactory development and bifurcations in Rathke's pouch with pituitary dysplasia. A comparable and highly variable phenotype in humans is septo-optic dysplasia. We have cloned and sequenced the human homologue HESX1 and screened for mutations in affected individuals using single-stranded conformational polymorphism analysis. Two siblings with septo-optic dysplasia were homozygous for a missense mutation within the HESX1 homeobox. This mutation resulted in the substitution of a highly conserved arginine residue (Arg53) by cysteine and led to a loss of in vitro DNA binding. Hence, a vital role for Hesx1/HESX1 in forebrain and pituitary development in mice and humans is suggested.
authors.affiliation: London Centre for Paediatric Endocrinology and Metabolism, Institute of Child Health, UK. m.dattani@ich.ucl.ac.uk
authors.forename: M T
authors.initials: MT
authors.lastname: Dattani
authors.forename: J P
authors.initials: JP
authors.lastname: Martinez-Barbera
authors.forename: P Q
authors.initials: PQ
authors.lastname: Thomas
authors.forename: J M
authors.initials: JM
authors.lastname: Brickman
authors.forename: R
authors.initials: R
authors.lastname: Gupta
authors.forename: J K
authors.initials: JK
authors.lastname: Wales
authors.forename: P C
authors.initials: PC
authors.lastname: Hindmarsh
authors.forename: R S
authors.initials: RS
authors.lastname: Beddington
authors.forename: I C
authors.initials: IC
authors.lastname: Robinson
mesh_terms: D000818:Animals; D001120:Arginine / Q000235:genetics; D051792:Basic Helix-Loop-Helix Proteins; D003545:Cysteine / Q000235:genetics; D005801:Genes, Homeobox; D005838:Genotype; D018257:Helix-Loop-Helix Motifs / Q000235:genetics*; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D020125:Mutation, Missense; D010641:Phenotype; D010903:Pituitary Gland, Anterior / Q000502:physiology; D016548:Prosencephalon / Q000502:physiology; D012097:Repressor Proteins; D012688:Septum Pellucidum / Q000002:abnormalities*; D000072056:Transcription Factor HES-1; D014158:Transcription, Genetic
chemical_list: D001120:Arginine; D051792:Basic Helix-Loop-Helix Proteins; D003545:Cysteine; D018398:Homeodomain Proteins; D012097:Repressor Proteins; D000072056:Transcription Factor HES-1; C489736:HESX1 protein, human; C489734:Hes1 protein, mouse; C489733:Hesx1 protein, mouse; C078493:HES1 protein, human