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. 1990 Mar;46(3):486–491.

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

J C Murray, D Y Nishimura, K H Buetow, H H Ardinger, M A Spence, R S Sparkes, R E Falk, P M Falk, R J M Gardner, E M Harkness, L P Glinski, R M Pauli, Y Nakamura, P P Green, A Schinzel
PMCID: PMC1683619  PMID: 2309700

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 (θ = 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.

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Selected References

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