Association between non syndromic cleft lip palate and microsatellite markers located in 6p

Background: Nonsyndromic cleft lip with or without cleft palate (NSCLP) is a common craniofacial developmental defect. Association studies have sugges ted that a clefting locus is located on chromosome GP nt ol near two possib le loci, Factor 13A (FI3A) in the region Gp 25-24 and HLA at 6p 21.3. Aim. To test the hypothesis on the possible presence of a major gene on chromoso me 6p associated with NSCLP. Patients and methods: We carried out all assoc iation study on a sample of unrelated NSCLP patients from multiplex (Mx) an d simplex (Sx) families, of their unaffected relatives and in control indiv iduals. DNA was analyzed with three PCR markers close to the putative NSCLP locus, dinucleotide repeats at loci D6S89, D6S109 and D6S105. PCR products were resolved by PAGE and visualized by silver staining. Statistical analy sis was performed by means of chi(2) log ratio. Results: Significant differ ences were observed when comparing the allele frequency distribution of D6S 89 in patients with NSCLP and controls and in patients with NSCLP-Mx and co ntrols. No significant differences were observed for patients with NSCLP-Sx . D6S109 and D6S105 showed no significant differences in any of the compari sons. Conclusions: Our results support the hypothesis that a NSCLP locus ma ps on 6p23 rely close to D6S89. Results for D6S109 and D6S105 do not show a clear association. Differences observed between NSCLP-MX and Sx families s eem to represent different etiologic entities. The results of the present s tudy, plus those already published for candidate loci, TGFA and MSX1, suppo rt the hypothesis that several interacting major genes participate in the e tiology of NSCLP.