Study of the PVRL1 Gene in Italian Nonsyndromic Cleft Lip Patients with or without Cleft Palate

Abstract

SummaryNonsyndromic cleft lip with or without cleft palate (CL/P) is a complex genetic trait and little is known about its aetiology. Recent investigations on rare clefting syndromes provided interesting clues about genes involved in face development. The PVRL1 gene encodes nectin1, a cell-to-cell adhesion molecule. Mutations in its sequence have been shown to cause the rare autosomal recessive syndrome CL/P-ectodermal dysplasia syndrome (CLPED1), while heterozygosity for the mutation W185X seemed to increase the risk of non syndromic CL/P in a population from northern Venezuela. In the present study, we screened 143 Italian CL/P patients for mutations in PVRL1. Three rare sequence variants in exon 3 that create amino-acid changes were detected in a total of 7 patients. Two of these mutations were not found in a panel of 292 unaffected controls, while the third was found in two controls. This study describes new mutations that may represent genetic risk factors for CL/P. Even though a study to look at the effects of the mutations on nectin1 function was not feasible, supporting evidence was reported, thus confirming the involvement of PVRL1 in the aetiology of non-syndromic CL/P malformation.

Mutation analysis of PVRL1 in patients with non-syndromic cleft of the lip and/or palate in Guangdong

“…Thus, PVRL1, and particularly its coding region, has become a focus point in NSCLP research (Scapoli et al, 2004(Scapoli et al, , 2006Tseng et al, 2006;Tongkobpetch et al, 2008;Zhao et al, 2009); however, the results from different regions are discrepant (Table 1).…”

“…Scapoli et al (2004Scapoli et al ( , 2006 did not find the W185X mutation in the populations studied, but instead found R199Q, R210H, and R212H mutations, affecting conserved amino acids (Avila et al, 2006). In Norway, the Philippines, and South America, 23 people carrying NSCLP-related mutations were identified; these mutations included 11 in the coding region, 7 in introns, and another 7 in the CpG islands.…”

Identification and characterization of two zebrafish nectin‐1 genes that are differentially expressed in the developing eye and brain

“…Mutations in the human nectin-1 gene are associated with the ZlotogoraOgü r syndrome and Margarita Island ectodermal dysplasia (Bustos et al, 1991;Suzuki et al, 2000;Sozen et al, 2001;Scapoli et al, 2006). These syndromes are characterized by sparse hair, scanty eyebrows, plantar hyperkeratosis, abnormal ears, dental anomalies, syndactyly, cleft lip with or without cleft palate, and occasionally mental retardation.…”

“…These syndromes are characterized by sparse hair, scanty eyebrows, plantar hyperkeratosis, abnormal ears, dental anomalies, syndactyly, cleft lip with or without cleft palate, and occasionally mental retardation. Non-syndromic cleft lip with or without cleft palate (Cl/P) may occur as isolated conditions without other recognizable anomalies (Sozen et al, 2001;Scapoli et al, 2006).…”

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

“…4 In a further screening of the same sample, we found three rare sequence variants in PVRL1 exon 3. 5 Interestingly, two PVRL1-related genes, PVR and PVRL2, which alike encode nectin-related Ig-class cell -cell adhesion molecules that serve as viral receptors, both map in chromosome segment 19q13.31 -q13.32, close to BCL3. Here is located OFC3, one of several non-syndromic CL/P susceptibility loci mapped in humans.…”