title: A homeobox gene, HLXB9, is the major locus for dominantly inherited sacral agenesis.
abstract: Partial absence of the sacrum is a rare congenital defect which also occurs as an autosomal dominant trait; association with anterior meningocoele, presacral teratoma and anorectal abnormalities constitutes the Currarino triad (MIM 176450). Malformation at the caudal end of the developing notochord at approximately Carnegie stage 7 (16 post-ovulatory days), which results in aberrant secondary neurulation, can explain the observed pattern of anomalies. We previously reported linkage to 7q36 markers in two dominantly inherited sacral agenesis families. We now present data refining the initial subchromosomal localization in several additional hereditary sacral agenesis (HSA) families. We excluded several candidate genes before identifying patient-specific mutations in a homeobox gene, HLXB9, which was previously reported to map to 1q41-q42.1 and to be expressed in lymphoid and pancreatic tissues.
authors.affiliation: Human Genetics Unit, School of Biochemistry and Genetics, University of Newcastle upon Tyne, UK.
authors.forename: A J
authors.initials: AJ
authors.lastname: Ross
authors.forename: V
authors.initials: V
authors.lastname: Ruiz-Perez
authors.forename: Y
authors.initials: Y
authors.lastname: Wang
authors.forename: D M
authors.initials: DM
authors.lastname: Hagan
authors.forename: S
authors.initials: S
authors.lastname: Scherer
authors.forename: S A
authors.initials: SA
authors.lastname: Lynch
authors.forename: S
authors.initials: S
authors.lastname: Lindsay
authors.forename: E
authors.initials: E
authors.lastname: Custard
authors.forename: E
authors.initials: E
authors.lastname: Belloni
authors.forename: D I
authors.initials: DI
authors.lastname: Wilson
authors.forename: R
authors.initials: R
authors.lastname: Wadey
authors.forename: F
authors.initials: F
authors.lastname: Goodman
authors.forename: K H
authors.initials: KH
authors.lastname: Orstavik
authors.forename: T
authors.initials: T
authors.lastname: Monclair
authors.forename: S
authors.initials: S
authors.lastname: Robson
authors.forename: W
authors.initials: W
authors.lastname: Reardon
authors.forename: J
authors.initials: J
authors.lastname: Burn
authors.forename: P
authors.initials: P
authors.lastname: Scambler
authors.forename: T
authors.initials: T
authors.lastname: Strachan
mesh_terms: D001483:Base Sequence; D001847:Bone Diseases / Q000151:congenital / Q000235:genetics*; D002878:Chromosomes, Human, Pair 1; D005260:Female; D005799:Genes, Dominant; D005801:Genes, Homeobox; D006239:Haplotypes; D006801:Humans; D008297:Male; D010375:Pedigree; D010641:Phenotype; D020161:Physical Chromosome Mapping; D012447:Sacrum / Q000002:abnormalities*