Mutation analysis of CLPTM 1 and PVRL 1 genes in patients with non-syndromic clefts of lip, alveolus and palate

Study of the Clptm1 Gene in South American Non-Syndromic Cleft Lip Patients With or Without Palate

“…We screened the entire sequence of exon 3 of the CLPTM1 gene, and adjacent intron and non-coding sequences, by simultaneous SSCP/ heteroduplex analysis for South American samples, followed by DNA sequencing of PCR products that contained apparent variants. Consequently, we determined a synonymous change (C�T resulting in a silent change, A88A) which was already reported by Turhani et al (24) and was particularly common in both patients and controls. And then we calculated mutant T allele frequencies for this synonymous change and tested for the presence of statistical significance using Fisher 's exact test.…”

“…CLPTM1 was also considered as a candidate gene which was initially identified at translocation break-point segregated 2-3 generation in a family with cleft lip and palate and it is localized at chromosome 19q13 (23). In another report by Turhani et al, it was screened for associated mutations with non-syndromic cleft lip with/without palate and they suggested that simultaneous occurance of CLPTM1 variations with a PVRL1 variant in the patients with non-syndromic cleft lip with/without palate could be a genetic risk factor, though the sample size were relatively small (24). However no other supportive reports in larger populations appeared lately.…”

“…Recently in another report, Turhani et al, have also analyzed the sequence changes in CLPTM1 gene together with PVRL1 variations in nsCL/P patients versus controls and reported no sequence changes in exons 4,5,7,9,11,12 and 14 in any of the patients and the controls, however, they reported some intronic changes in the following introns: two changes in IVS13 and IVS2, one in IVS3, IVS6 and IVS7 as well as several synonomous changes two of which are in exon 8 (Pro309Pro and Gly331Gly) and one in exon 3 (Ala88Ala). Also they reported that a PVRL1 variant, Glu441-Gly442 ins Glu, was found more frequently in the nsCL/P patients and none of the controls (24). However, they suggested that simultaneous occurrence of an intron change, exon changes of the CLPTM1 gene and Glu441-Gly442 ins Glu mutation of PVRL1 could be a genetic factor for nonsyndromic clefts.…”

PVRL1 as a Candidate Gene for Nonsyndromic Cleft Lip With or Without Cleft Palate: No Evidence for the Involvement of Common or Rare Variants in Southern Han Chinese Patients

“…A follow-up study from the same research team identified heterozygosity of the nonsense W185 · mutation as a genetic risk factor of NSCL/P in a northern Venezuelan population (Sozen et al, 2001). These findings established PVRL1 as a promising candidate gene of NSCL/P, and several subsequent investigations have been conducted on the coding regions of PVRL1 (Item et al, 2003;Scapoli et al, 2004Scapoli et al, , 2006Turhani et al, 2005;Avila et al, 2006;Ichikawa et al, 2006;Tseng et al, 2006;Sozen et al, 2009;Zhao et al, 2009;Shu et al, 2011). Nevertheless, results from different ethnic groups have been conflicting (the findings of these studies are summarized in Table 1).…”

Lack of mutations in the PVRL3 gene in North American caucasians with non-syndromic cleft lip/palate

“…Genetic linkage and association studies have implicated many loci in the pathogenesis of nsCLP, including PVRL1, which encodes nectin-1, a cell adhesion molecule (Reymond et al, 2000;Satoh-Horikawa et al, 2000). Homozygous loss-of-function mutations in PVRL1 result in a rare recessive CLP syndrome, CLPED1 (Suzuki et al, 2000), and heterozygous PRVL1 variants have been associated with nsCLP (Sozen et al, 2001;Turhani et al, 2005;Avila et al, 2006;Neiswanger et al, 2006;Scapoli et al, 2006;Tseng et al, 2006).Two other nectin-family paralogues, PVR and PVRL2, were recently evaluated as candidate genes for nsCLP and found to show evidence of genetic association (Warrington et al, 2006). Here, we describe the analysis of another member of the nectin gene family, PVRL3, which encodes nectin-3, as a candidate gene for nsCLP.…”