Recurrencia familiar del labio leporino con o sin fisura velopalatina de origen no sindrómico en poblaciones de Chile / Familial recurence of non syndromic cleft lip with or without cleft palate in Chilean populations

Background: The presence of major genes in the susceptibility of non syndromic cleft lip with or without cleft palate (CL/P) in Chile has been postulated, considering the high prevalence and familial aggregation of this condition. Aim: To study the familial recurrence of CL/P in Chile. Patients and methods: The recurrence risk of CL/P was studied in 217 extended pedigrees where 33 (15.2 percent) were multiplex (21 male and 12 female propositi). These multiplex extended pedigrees (with more than one affected individual) represented 75 nuclear pedigrees, constituted by 840 males and 803 females and are the basic information of this study. Results: A significantly higher frequency of affected males (4.15 percent) than affected females (2.27 percent) was observed, independent of the difference in number of propositi by sex. Even though no differences were observed between families where both parents were unaffected, compared to those with only one affected parent, a higher proportion of affected descendants was found when the affected propositi was the mother. In multiplex families, the recurrence risk, according to the genetic proximity to the proband, was 10.1, 3.6 and 3.3 percent respectively for first, second and third degree relatives. The figures were 1.5, 0.5 and 0.4 percent respectively, when adjusted to the 217 extended pedigrees. Considering that the risk for the general population in Chile is approximately 0.16 percent, it is 10.3, 3.2 and 2.6 times higher among affected families. Conclusions: The high heritability of CL/P and the risk encountered for the Chilean population supports the hypothesis of major genes involved in its susceptibility

Asociación entre el fenotipo fisura labiopalatina no sindrómica y marcadores de microsatélite ubicados en 4q / 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 cleftinglocus is located on chromosome 4q at or near two microsatellite markers D4S175 and D4S192. Aim: 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 unaffected 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, dinucleotide repeats D4S175 and D4S192. PCR products were resolved by PAGE and visualized by silver staining. Statistical analysis was performed by means of c2 log ratio. Results: Significant differences between NSCLP and controls were observed when comparing the allele frequency distribution of D4S192 both in the total sample as well as in NSCLP-multiplex and simplex cases. No significant differences for D4S175 were observed in any of the comparisons. 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 marker D4S192. No differences were observed between NSCLP multiplex and simplex cases versus controls, implying that they do not represent different etiologic entities. The results of the present and previous studies in the same group of patients support the hypothesis that several major interacting genes participate in the etiology of NSCLP

Estudio de asociación entre la fisura labiopalatina no sindrómica y marcadores de microsatélite ubicados en 6p / Association study 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 suggested that a clefting locus is located on chromosome 6p at or near two possible loci, Factor 13A (FI3A) in the region 6p 25-24 and HLA at 6p 21.3. Aim. To test the hypothesis on the possible presence of a major gene on chromosome 6p associated with NSCLP. Patients and methods: We carried out an association study on a sample of unrelated NSCLP patients from multiplex (Mx) and simplex (Sx) families, of their unaffected relatives and in control individuals. 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 analysis was performed by means of c2 log ratio. Results: Significant differences were observed when comparing the allele frequency distribution of D6S89 in patients with NSCLP and controls and in patients with NSCLP-Mx and controls. No significant differences were observed for patients with NSCLP-Sx. D6S109 and D6S105 showed no significant differences in any of the comparisons. Conclusions: Our results support the hypothesis that a NSCLP locus maps on 6p23 very close to D6S89. Results for D6S109 and D6S105 do not show a clear association. Differences observed between NSCLP-MX and Sx families seem to represent different etiologic entities. The results of the present study, plus those already published for candidate loci, TGFA and MSX1, support the hypothesis that several interacting major genes participate in the etiology of NSCLP