Evidence of Linkage to 6p23 and Genetic Heterogeneity in Nonsyndromic Cleft Lip with or without Cleft Palate

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

“…Additional evidence for the involvement of 6p was provided by Davies et al (1995), who reported three independent chromosome rearrangements in this region associated with OFC. During our linkage studies, using markers mapping to 6p23 (OFC1) and a large family set, evidence of linkage and locus heterogeneity with 60 % of families linked to D6S259 was observed (Scapoli et al 1997). Altogether, these studies suggest that a gene on 6p23 may play a role in clefting (Carinci et al 2000).…”

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

“…In recent years, different groups have investigated the localisation of a putative major OFC gene providing, sometimes, conflicting results . In previous linkage studies, using markers on chromosomes 6p23 and 2p13, we detected significant genetic heterogeneity (Scapoli et al 1997 ;Pezzetti et al 1998). These results indicated that 30 out of 38 families had a posterior probability 50 % in favour of linkage to the 6p23 region, while 14 out of 38 were linked to the 2p13 region.…”

“…Indeed, LOD scores calculated under the hypothesis of locus heterogeneity were negative or inconclusive (data not shown). We previously obtained evidence of linkage and genetic heterogeneity in a study regarding the 6p23 region (Scapoli et al 1997). A reanalysis of the chromosome 1 data, sorting out 6p23 linked and unlinked families, indicates that the two groups are homogeneous.…”

“…The pedigree collection of 38 families was extensively described in a previous report (Scapoli et al 1997). Briefly, all families were collected from regions of northeastern Italy, ascertained through the Archive for Cleft Lip and Palate Cases of the Clinic of Oral-Maxillofacial Surgery, General Hospital of Vicenza, Italy.…”

“…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.…”