title: The gene responsible for X-linked cleft palate (CPX) in a British Columbia native kindred is localized between PGK1 and DXYS1.
abstract: Human craniofacial malformations are a class of common congenital anomalies in which the etiology is heterogeneous and often poorly understood. To better delineate the molecular basis of craniofacial development, we have undertaken a series of experiments directed toward the isolation of a gene involved in human secondary palate formation. DNA marker linkage studies have been performed in a large British Columbia (B.C.) Native family in which cleft palate segregates as an X-linked trait. We have examined 62 family members, including 15 affected males and 8 obligate carrier females. A previous clinical description of the clefting defect in this kindred included submucous cleft palate and bifid or absent uvula. Our recent reevaluation of the family has indicated that ankyloglossia (tongue-tie) is also a feature of X-linked cleft palate in some of the affected males and carrier females. Ankyloglossia has previously been associated with X-linked cleft palate in an Icelandic kindred in which a gene responsible for cleft palate (CPX) was assigned to the Xq21.3-q22 region between DXYS12 and DXS17. For the B.C. kindred reported here, we have mapped the gene responsible for cleft palate and/or ankyloglossia to a more proximal position on the X chromosome. No recombination was observed between B.C. CPX and the DNA marker DXS72 (peak lod score [Zmax] = 7.44 at recombination fraction [theta] = .0) localized to Xq21.1. Recombination was observed between CPX and PGK1 (Zmax = 7.35 at theta = .03) and between CPX and DXYS1 (Zmax = 5.59 at theta = .04). These recombination events localize B.C. CPX between PGK1 and DXYS1 in the Xq13-q21.31 region.
authors.affiliation: Department of Medical Genetics, University of British Columbia, Vancouver, Canada.
authors.forename: S M
authors.initials: SM
authors.lastname: Gorski
authors.forename: K J
authors.initials: KJ
authors.lastname: Adams
authors.forename: P H
authors.initials: PH
authors.lastname: Birch
authors.forename: J M
authors.initials: JM
authors.lastname: Friedman
authors.forename: P J
authors.initials: PJ
authors.lastname: Goodfellow
mesh_terms: D015139:Blotting, Southern; D002972:Cleft Palate / Q000235:genetics*; D005260:Female; D008040:Genetic Linkage / Q000235:genetics*; D005819:Genetic Markers / Q000235:genetics; D006579:Heterozygote; D006801:Humans; D008297:Male; D010375:Pedigree; D011110:Polymorphism, Genetic / Q000235:genetics; D014059:Tongue / Q000002:abnormalities; D014960:X Chromosome
chemical_list: D005819:Genetic Markers