Linkage of an autosomal dominant clefting syndrome (Van der Woude) to loci on chromosome Iq

Am J Hum Genet. 1990 Mar;46(3):486-91.


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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Chromosomes, Human, Pair 1*
  • Cleft Lip / genetics*
  • Cleft Palate / genetics*
  • DNA Probes
  • Genetic Linkage*
  • Genetic Markers
  • Humans
  • Pedigree
  • Syndrome


  • DNA Probes
  • Genetic Markers