title: Linkage of an autosomal dominant clefting syndrome (Van der Woude) to loci on chromosome Iq.
abstract: Van der Woude syndrome (VWS) is an autosomal dominant disorder in which affected individuals have one or more of the following manifestations: cleft lip, cleft palate, hypodontia, or paramedian lower-lip pits. VWS is a well-characterized example of a single-gene abnormality that disturbs normal craniofacial morphogenesis. As a first step in identifying genes involved in human development, we used a candidate-gene-and-region approach to look for a linkage to VWS. Six families with 3 or more generations of affected individuals were studied. Evidence for linkage (theta = 0.02, lod score = 9.09) was found between the renin (REN) gene on 1q and VWS. Other linked loci included CR1, D1S58, and D1S53. The genes for laminin B2 (LAMB2), a basement-membrane protein, and for decay-accelerating factor (DAF) were studied as possible candidate genes on 1q. Recombinants between VWS and both LAMB2 and DAF excluded these genes from a causal role in the etiology of VWS for the families studied in this report. Multipoint linkage analysis indicated that the VWS locus was flanked by REN and D1S65 at a lod score of 10.83. This tight linkage with renin and other nearby loci provides a first step in identifying the molecular abnormality underlying this disturbance of human development.
authors.affiliation: Department of Pediatrics, University of Iowa, Iowa City.
authors.forename: J C
authors.initials: JC
authors.lastname: Murray
authors.forename: D Y
authors.initials: DY
authors.lastname: Nishimura
authors.forename: K H
authors.initials: KH
authors.lastname: Buetow
authors.forename: H H
authors.initials: HH
authors.lastname: Ardinger
authors.forename: M A
authors.initials: MA
authors.lastname: Spence
authors.forename: R S
authors.initials: RS
authors.lastname: Sparkes
authors.forename: R E
authors.initials: RE
authors.lastname: Falk
authors.forename: P M
authors.initials: PM
authors.lastname: Falk
authors.forename: R J
authors.initials: RJ
authors.lastname: Gardner
authors.forename: E M
authors.initials: EM
authors.lastname: Harkness
mesh_terms: D002878:Chromosomes, Human, Pair 1; D002971:Cleft Lip / Q000235:genetics*; D002972:Cleft Palate / Q000235:genetics*; D015342:DNA Probes; D008040:Genetic Linkage; D005819:Genetic Markers; D006801:Humans; D010375:Pedigree; D013577:Syndrome
chemical_list: D015342:DNA Probes; D005819:Genetic Markers