STUDY OF THE CLPTM1 GENE IN SOUTH AMERICAN NON-SYNDROMIC CLEFT LIP PATIENTS WITH OR WITHOUT PALATE

Mehmet A Sözen,Richard A Spritz,Marie M Tolarova

doi:10.29333/ejgm/82594

Abstract

Aim: The CLPTM1 gene is considered as a candidate gene based on the fact that it is localized in the human chromosomal region 19q13 which maps in the candidate region OFC3. This study aims to test the involvement of this candidate gene, CLPTM1, in non-syndromic cleft lip with or without cleft palate (CL/P, MIM 119530) and to analyze particularly a CLPTM1 variant, A88A if there is an allelic association with non-syndromic cleft lip and palate. Methods: A total of 171 non-syndromic cleft lip patients with or without palate and 181 healthy controls from Venezuela and a total of 92 non-syndromic CL/P patients and 76 healthy controls from Argentina were screened for CLPTM1 Exon 3 variation, A88A using Single Stranded Conformation Polymorphism technique. Results: We found no significant difference for the A88A mutation of CLPTM1 gene between nsCL/P patients and controls neither in Venezuela nor in Argentina, although the first cohort from Venezuela showed a significant difference in terms of CLPTM1 88A mutant allele frequency in particular. Conclusion: The CLPTM1 variant, A88A, was not found to be associated with the disease in the two populations studied. These data suggest that CLPTM1 gene do not seem to participate in the development of nsCL/P in the South American populations studied. These results also suggest that larger sample size in the study of the allelic association might be more informative than the smaller ones.

Highlights

Cleft lip with/without palate (CL/P)is is perhaps the most common major birth defect and occurs in approximately0.4-2 per 1000 liveborn infants in most populations depending on the geographic origin and ethnic background worldwide [1,2] In man, about 30% of cases are syndromic and in the rest (70%) of them, CL/P occurs as an isolated, sporadic defect where the clefts are without other anomalies
Turhani et al, have analyzed the sequence changes in CLPTM1 gene together with PVRL1 variations in non-syndromic cleft lip with/ without palate (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, 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)
We screened the entire sequence of exon 3 of the CLPTM1 gene, and adjacent intron and non-coding sequences, by simultaneous single stranded conformation polymorphism (SSCP)/ heteroduplex analysis for South American samples, followed by DNA sequencing of polymerase chain reaction (PCR) products that contained apparent variants

Summary

Introduction

0.4-2 per 1000 liveborn infants in most populations depending on the geographic origin and ethnic background worldwide [1,2] In man, about 30% of cases are syndromic and in the rest (70%) of them, CL/P occurs as an isolated, sporadic defect where the clefts are without other anomalies Such ‘non-syndromic’ CL/P (nsCL/P, MIM 119530) is a polygenic, multifactorial disorder, showing complex inheritance and thought that both genes and environmental factors, contributing either independently or in combination, are responsible for that kind of clefting (3- 7). They reported that a PVRL1 variant, Glu441Gly442 ins Glu, was found more frequently in the nsCL/P patients and none of the controls [24] 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. A mutation screening for exon 3 of CLPTM1 gene were attempted followed by the calculation of the allele frequencies and an allelic association between the synonymous mutation A88A of the CLPTM1 gene and non-syndromic cleft lip with or without palate malformation was tested in the Venezuelan, and Argentinian populations

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