Linkage analysis of neurofibromatosis 1. Study of a homogeneous North Italian population with five DNA markers of chromosome 17. DNA analysis of genetic diseases: state of art in Italy.

Von Recklinghausen peripheral neurofibromatosis ( NF- 1 ), one of the most frequent , ubiquitous , clinically relevant, and progressive monogenic disorders in man , is inherited as an autosomal dominant condition with variable expressivity, and complete (100%) penetrance. In North-East Italy we have estimated the NF1 frequency as 1 : 4292 inhabitants ( 2 . 33 per I0,000; 95% CI 1.79 -2.87 ) , the proportion of sporadic cases as 0.56 (SE 0.09) and the mutation rate as 6.5 x 1 0 - s gametes per generation ( 9 5% c i 5 . 0 - 8 . 1 ). The locus for NF1 has been mapped to chromosome 17 and there is now general agreement, by means of linkage analysis, in assigning the gene to the proximal long arm. The recent identification of two unrelated affected individuals with balanced trans location involving chromosome 17q11.2 definitely seems to localize the gene . In order to verify the apparent genetic homogeneity of the NF1 mutation, we performed a genetic analysis using five loci tightly linked to NF1 in a sample of NF1 families, homogeneous for ascertainment and coming from a defined geographical area.