Association between nonsyndromic cleft lip/palate with microsatellite markers located in 4q

Background: Nonsyndromic cleft lip with, or without cleft palate (NSCLP) is a common craniofacial defect. Association studies have suggested that a cl efting locus is located on chromosome 4q at or near two microsatellite mark ers D4S175 and D4S192. Abl: To test the hypothesis on the possible presence of a clefting locus on chromosome 4q. Material and methods: We carried out an association study on a sample of unrelated NSCLP patients, of their una ffected relatives and in controls. Both probands and relatives were further analyzed depending if they originated from simplex or multiplex families. DNA was analyzed with two PCR markers close to the putative, NSCLP locus, d inucleotide repeats D4S175 and D4S192. PCR products were resolved by PAGE a nd visualized by silver staining. Statistical analysis was performed by mea ns of chi 2 log ratio. Results: Significant differences between NSCLP and c ontrols were observed when comparing the allele frequency distribution of D 4S192 both in the total sample as well as in NSCLP-multiplex and simplex ca ses. No significant differences for D4S175 were observed in any of the comp arisons. Unaffected relatives showed significant differences with controls both for D4S175 and D4S192. Conclusions: Our results support the hypothesis that a NSCLP locus maps on chromosome 4q close to the microsatellite marke r D4S192. No differences were observed between NSCLP multiplex and simplex cases versus controls, implying that they do not represent different etiolo gic entities. The results of the present and previous studies in the same g roup of patients support the hypothesis that several major interacting gene s participate in the etiology of NSCLP.