MICROSATELLITE DNA AS A MARKER FOR MAPPING OF LOCI LINKED TO CRANIOFACIAL MALFORMATIONS

Cleft Lip with or without cleft palate (CL +/- P) is one of most common congenital orofacial anomaly, with a frequency of 1/700-1/1,000 live births among Caucasians. This embryopathy is due to a failure of nasal processes and palatal shelves fusion. Approximately 20 % of patients have a positive family history of CL +/- P, and thus genetic factors are thought to be important in its etiology. Four different chromosomal regions, 6p23-25, 2p13, 17q21.1 and 1q21, have been claimed to contain a CL +/- P locus. In our study we investigated the possible CL +/- P locus of chromosome 6p23. To this purpose we selected a group of markers, which map on this chromosome region, to analyse a large sample of families. Twentyone families characterized by the presence of at least two affected CL +/- P individuals, arising from north-eastern Italy, were enrolled in this study. DNA was analyzed with five highly informative PCR markers close to the putative CL +/- P locus: 1 VNTR factor 13A, and 4 dinucleotide repeats at loci EDN1, D6S89, D6S109, D6S105. Our results demonstrate that nonsyndromic familiar CL +/- P is heterogeneous; these data are in agreement with the idea of a model of a dominant major gene modified by additional genetic and/or enviromental factors. So it is possible that different chromosomal region are involved in etiology of the disease. Our linked families showed an autosomal dominant inheritance with incomplete penetrance. Finally, CL +/- P locus maps on 6p23 very close to, or at the microsatellite marker D6S89.