Suggestive Linkage between Markers on Chromosome 19q13.2 and Nonsyndromic Orofacial Cleft Malformation

Linkage analysis of three candidate regions of chromosome 1 in nonsyndromic familial orofacial cleft

“…Stein et al (1995) postulated the presence of the OFC3 locus at the 19q13n2 region, containing the oncogene BCL3. We were unable to confirm these results in our family set, using parametric linkage analysis ), but linkage disequilibrium was detected with markers close to the gene (Wyszynski et al 1997 ;Martinelli et al 1998).…”

“…Many molecular genetic investigations supported major gene\oligogenic models in the development of the cleft, with evidence of involved loci in different chromosome regions. Of note, there is evidence for a clefting locus on 6p23 (OFC1) (Eiberg et al 1987 ;Carinci et al 1995 ;Davies et al 1995 ;Scapoli et al 1997), 2p13 (OFC2) (Ardinger et al 1989 ;Mitchell, 1997 ;Pezzetti et al 1998), 19q13 (OFC3) (Stein et al 1995 ;Wyszynski et al 1997 ;Martinelli et al 1998), 4q25-31 (Beiraghi et al 1994Healey et al 1994) and 17q21 (RARA ) (Chenevix-Trench et al 1992 ;Shaw et al 1993). Since the aetiology of OFC seems to be quite complex, it is very likely that several loci may contribute to this malformation.…”

Linkage analysis of candidate endothelin pathway genes in nonsyndromic familial orofacial cleft

“…Stein et al (1995) found evidence of locus heterogeneity and linkage with BCL3, a proto-oncogene mapping on 19q13.2. In other studies, linkage disequilibrium for BCL3 was observed using the transmission disequilibrium test (TDT), while no linkage or heterogeneity was obtained using the LOD score method (Wyszynski et al 1997 ;Martinelli et al 1998).…”

Linkage disequilibrium analysis of two genes mapping on OFC3: PVR and PVRL2

“…6,7 We previously analysed the OFC3 candidate region using a sample of 40 multiplex pedigrees and microsatellite markers, and obtained evidence of linkage and linkage disequilibrium with APM and TDT analyses. 8 Recently, Warrington et al 9 searched for an association between orofacial clefts and mutations in the PVR and PVRL2 genes, using samples from different populations. They found a statistically significant association in the South American and Iowa populations for an allelic variant in the PVR gene, while the PVR marker did not show any significant association in the Danish sample.…”