title: A submicroscopic deletion in Xq26 associated with familial situs ambiguus.
abstract: Abnormal left-right-axis formation results in heterotaxy, a multiple-malformation syndrome often characterized by severe heart defects, splenic abnormalities, and gastrointestinal malrotation. Previously we had studied a large family in which a gene for heterotaxy, HTX1, was mapped to a 19-cM region in Xq24-q27.1. Further analysis of this family has revealed two recombinations that place HTX1 between DXS300 and DXS1062, an interval spanning approximately 1.3 Mb in Xq26.2. In order to provide independent confirmation of HTX1 localization, a PCR-based search for submicroscopic deletions in this region was performed in unrelated males with sporadic or familial heterotaxy. A cluster of sequence-tagged sites failed to amplify in an individual who also had a deceased, affected brother. FISH identified the mother as a carrier of the deletion, which arose as a new mutation from the maternal grandfather. The deletion interval spans 600-1,100 kb and lies wholly within the 1.3-Mb region identified by recombination. Discovery of this deletion supports localization of HTX1 to Xq26.2 and reveals the first molecular-genetic abnormality associated with human left-right-asymmetry defects.
authors.affiliation: Department of Pathology, Baylor College of Medicine, Houston, TX 77030, USA.
authors.forename: G B
authors.initials: GB
authors.lastname: Ferrero
authors.forename: M
authors.initials: M
authors.lastname: Gebbia
authors.forename: G
authors.initials: G
authors.lastname: Pilia
authors.forename: D
authors.initials: D
authors.lastname: Witte
authors.forename: A
authors.initials: A
authors.lastname: Peier
authors.forename: R J
authors.initials: RJ
authors.lastname: Hopkin
authors.forename: W J
authors.initials: WJ
authors.lastname: Craigen
authors.forename: L G
authors.initials: LG
authors.lastname: Shaffer
authors.forename: D
authors.initials: D
authors.lastname: Schlessinger
authors.forename: A
authors.initials: A
authors.lastname: Ballabio
authors.forename: B
authors.initials: B
authors.lastname: Casey
mesh_terms: D000015:Abnormalities, Multiple / Q000235:genetics*; D019521:Body Patterning / Q000235:genetics*; D005260:Female; D017353:Gene Deletion; D008040:Genetic Linkage; D018392:Genomic Imprinting; D006330:Heart Defects, Congenital / Q000235:genetics; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D010375:Pedigree; D016324:Sequence Tagged Sites; D012729:Sex Chromosome Aberrations / Q000235:genetics*; D012857:Situs Inversus / Q000235:genetics; D013154:Spleen / Q000002:abnormalities; D014781:Viscera / Q000002:abnormalities; D014960:X Chromosome / Q000235:genetics*