title: Possible relationship between the van der Woude syndrome (vWS) locus and nonsyndromic cleft lip with or without cleft palate (NSCL/P).
abstract: Cleft lip with or without cleft palate (CL/P) is one of the most common congenital malformations in humans occurring with a birth prevalence of approximately 1:1,000. CL/P may be part of a defined syndrome, sequence or association, although most individual or familial cases present as an isolated (nonsyndromic) malformation (NSCL/P). Inheritance is generally regarded as multigenic although, in some families, NSCL/P seemingly segregates as a monogenic trait. On the other hand, van der Woude syndrome (vWS) is a rare autosomal dominant with cardinal features of lower-lip pits (LLP) and CL/P or cleft palate (alone). Since none of these traits is present in all mutation carriers, some individual or familial vWS cases, especially those lacking LLP, are indiscernible from NSCL/P, raising the question whether allelic variation at the vWS locus could underlie NSCL/P. This question was addressed using parametric linkage (LOD score) analysis in 21 multiplex NSCL/P families based on a tightly linked microsatellite marker (D1S3753), and nonparametric analysis using the transmission/disequilibrium test (GTDT) in 106 NSCL/P triads and selecting markers D1S205, D1S491, and D1S3753. No evidence for linkage of NSCL/P to vWS was found on the 21 families using the LOD score approach. In contrast, TDT yielded a significant P value of 0.04 for D1S205, supporting involvement of vWS in NSCL/P in a complex, modifying/polygenic manner rather than as a monogenic/major disease locus.
authors.affiliation: Biochimie et Biologie Moléculaire, Hôpital d'Enfants Armand-Trousseau, Assistance Publique-Hôpitaux de Paris, 26 Avenue du Docteur Arnold-Necker, 75571 Paris Cedex 12, France. biochimie.trousseau@trs.ap-hop-paris.fr
authors.forename: C
authors.initials: C
authors.lastname: Houdayer
authors.forename: C
authors.initials: C
authors.lastname: Bonaïti-Pellié
authors.forename: C
authors.initials: C
authors.lastname: Erguy
authors.forename: V
authors.initials: V
authors.lastname: Soupre
authors.forename: M G
authors.initials: MG
authors.lastname: Dondon
authors.forename: L
authors.initials: L
authors.lastname: Bürglen
authors.forename: E
authors.initials: E
authors.lastname: Cougoureux
authors.forename: R
authors.initials: R
authors.lastname: Couderc
authors.forename: M P
authors.initials: MP
authors.lastname: Vazquez
authors.forename: M
authors.initials: M
authors.lastname: Bahuau
mesh_terms: D000483:Alleles; D002971:Cleft Lip / Q000235:genetics*; D002972:Cleft Palate / Q000235:genetics*; D005260:Female; D005838:Genotype; D006579:Heterozygote; D006801:Humans; D007569:Jaw Abnormalities; D015810:Linkage Disequilibrium / Q000235:genetics; D008126:Lod Score; D008297:Male; D018895:Microsatellite Repeats / Q000235:genetics; D010375:Pedigree