title: Nonsyndromic cleft lip with or without cleft palate: evidence of linkage to BCL3 in 17 multigenerational families.
abstract: Nonsyndromic cleft lip with or without cleft palate (CL/P) is a common craniofacial developmental defect. Recent segregation analyses have suggested that major genes play a role in the etiology of CL/P. Linkage to 22 candidate genes was tested in 11 multigenerational families with CL/P, and 21 of these candidates were excluded. APOC2, 19q13.1, which is linked to the proto-oncogene BCL3, gave suggestive evidence for linkage to CL/P. The study was expanded to include a total of 39 multigenerational CL/P families. Linkage was tested in all families, using an anonymous marker, D19S178, and intragenic markers in BCL3 and APOC2. Linkage was tested under two models, autosomal dominant with reduced penetrance and affecteds only. Homogeneity testing on the two-point data gave evidence of heterogeneity at APOC2 under the affecteds-only model. Both models showed evidence of heterogeneity, with 43% of families linked at zero recombination to BCL3 when marker data from BCL3 and APOC2 were included. A maximum multipoint LOD score of 7.00 at BCL3 was found among the 17 families that had posterior probabilities > = 50% in favor of linkage. The transmission disequilibrium test provided additional evidence for linkage with the 3 allele of BCL3 more often transmitted to affected children. These results suggest that BCL3, or a nearby gene, plays a role in the etiology of CL/P in some families.
authors.affiliation: University of Texas Medical School at Houston 77225, USA.
authors.forename: J
authors.initials: J
authors.lastname: Stein
authors.forename: J B
authors.initials: JB
authors.lastname: Mulliken
authors.forename: S
authors.initials: S
authors.lastname: Stal
authors.forename: D L
authors.initials: DL
authors.lastname: Gasser
authors.forename: S
authors.initials: S
authors.lastname: Malcolm
authors.forename: R
authors.initials: R
authors.lastname: Winter
authors.forename: S H
authors.initials: SH
authors.lastname: Blanton
authors.forename: C
authors.initials: C
authors.lastname: Amos
authors.forename: E
authors.initials: E
authors.lastname: Seemanova
authors.forename: J T
authors.initials: JT
authors.lastname: Hecht
mesh_terms: D000081242:B-Cell Lymphoma 3 Protein; D002971:Cleft Lip / Q000235:genetics*; D002972:Cleft Palate / Q000235:genetics*; D005260:Female; D008040:Genetic Linkage; D006801:Humans; D008126:Lod Score; D008297:Male; D010375:Pedigree; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D014157:Transcription Factors
chemical_list: D000081242:B-Cell Lymphoma 3 Protein; C000631344:BCL3 protein, human; C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins; D014157:Transcription Factors