title: From VACTERL-H to heterotaxy: variable expressivity of ZIC3-related disorders.
abstract: The ZIC3 gene encodes a zinc finger protein which functions as a transcription factor in early stages of left-right body axis formation. Mutations in this X-linked gene cause a variety of clinical manifestations including heterotaxy, complex or isolated heart defect as well as other midline urogenital and hindgut malformations. We report a four generation family with X-linked heterotaxy associated with a deletion of the ZIC3 gene at Xq26.3. The index fetus of our proband showed classical features of heterotaxy while her maternal uncle and one brother had imperforate anus and her other brother had features suggestive of VACTERL-H without heterotaxy. A 1.4 Mb deletion in Xq26.3 including the ZIC3 gene was found in the fetus. Six females in the family were found to be asymptomatic carriers. Our report indicates that some of the cases with VACTERL-H syndrome may be caused by a mutation or deletion of the ZIC3 gene.
authors.affiliation: The Prenatal Diagnosis and Medical Genetics Program, Department of Obstetrics and Gynecology, Mount Sinai Hospital, University of Toronto, Ontario, Canada.
authors.forename: Brian
authors.initials: B
authors.lastname: Chung
authors.forename: Lisa G
authors.initials: LG
authors.lastname: Shaffer
authors.forename: Sarah
authors.initials: S
authors.lastname: Keating
authors.forename: Joan
authors.initials: J
authors.lastname: Johnson
authors.forename: Bret
authors.initials: B
authors.lastname: Casey
authors.forename: David
authors.initials: D
authors.lastname: Chitayat
mesh_terms: D000328:Adult; D005260:Female; D040181:Genetic Diseases, X-Linked / Q000235:genetics*; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D010375:Pedigree; D014157:Transcription Factors / Q000235:genetics*
chemical_list: D018398:Homeodomain Proteins; D014157:Transcription Factors; C491595:ZIC3 protein, human