Molecular characterization of Fanconi anaemia group C (FAC) gene polymorphisms.

Fanconi anaemia (FA) is a genetically heterogeneous disease with defects in at least five genes. The gene for complementation group C (FAC) has been cloned and mapped to chromosome 9q22.3 in the interval between D9S280 and D9S287. Linkage analysis is a rapid tool for the exclusion of FA families from complementation group C. The currently available markers are informative microsatellites flanking FAC and an intragenic restriction fragment length polymorphism (RFLP). In this paper, the identification of three CA polymorphic repeats localized in introns-1a, 2 and 3 and one rare variant in exon 2 are reported. The new microsatellites will enable more accurate analysis not only of FA but also in families affected by multiple self-healing squamous epitheliomata (ESS1) and nevoid basal cell carcinoma (NBCCS), since the genes of both syndromes have been mapped in the same interval as FAC.

Scanning the first part of the neurofibromatosis type 1 gene by RNA-SSCP: identification of three novel mutations and of two new polymorphisms.

Neurofibromatosis type 1 (NF1) of von Recklinghausen is a common autosomal dominant disorder, characterized by peripheral neurofibromas, café-au-lait spots and Lisch nodules of the iris. The high mutation rate at the NF1 locus results in a wide range of molecular abnormalities. We have scanned 14 different exons from the first part of the NF1 gene using the RNA-single strand conformation polymorphism (RNA-SSCP) method in a series of 40 NF1 patients. Three novel mutations, two nonsense and one missense, and two polymorphisms have been detected in familial cases. Genotype-phenotype correlations have been investigated, but no particular association has been detected. After this screening, the majority of NF1 chromosomes has not yet been characterized, confirming the difficulty in detecting the defect underlying NF1 in most families, even following extensive DNA analysis.