The Dutch FAMMM family material: clinical and genetic data.

Department of Dermatology, University Medical Center Leiden, The Netherlands.
Cytogenetics and cell genetics 02/1992; 59(2-3):161-4. DOI: 10.1159/000133232
Source: PubMed
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The most common hereditary melanoma susceptibility disorder is the familial atypical multiple mole-melanoma (FAMMM) syndrome. FAMMM is regarded as an ideal natural model to study the very complex pathologic mechanism of melanoma. In 1994, cloning of the melanoma susceptibility gene CDKN2A was thought to give answers to many questions on genotype-phenotype correlations in familial melanoma. Today, 4 y later, germline mutations cosegregate with melanoma in only 40%–50% of the families predisposed to this disease. The hunt for genes and modifying genes is on again. Through the years the very well-characterized Dutch FAMMM families have proven to be valuable study subjects in melanoma research. This paper describes over 10 y of melanoma research illustrated by research performed in the Dutch FAMMM families.Keywords: CDKN2A, hereditary melanoma, melanocortin 1 receptor
    Journal of Investigative Dermatology Symposium Proceedings 08/1999; 4(1):50-54. DOI:10.1038/sj.jidsp.5640181 · 3.73 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Risk factors for melanoma include environmental (particularly ultraviolet exposure) and genetic factors. In rare families, susceptibility to melanoma is determined by high penetrance mutations in the genes CDKN2A or CDK4, with more common, less penetrant genes also postulated. A further, potent risk factor for melanoma is the presence of large numbers of melanocytic nevi so that genes controlling nevus phenotype could be such melanoma susceptibility genes. A large Australian study involving twins aged 12 y of predominantly U.K. ancestry showed strong evidence for genetic influence on nevus number and density. We carried out essentially the same study in the U.K. to gain insight into gene–environment interactions for nevi. One hundred and three monozygous (MZ) and 118 dizygous (DZ) twin pairs aged 10–18 y were examined in Yorkshire and Surrey, U.K. Nevus counts were, on average, higher in boys (mean = 98.6) than girls (83.8) (p =0.009) and higher in Australia (110.4) than in the U.K. (79.2, adjusted to age 12 y, p <0.0001), and nevus densities were higher on sun-exposed sites (92 per m2) than sun-protected sites (58 per m2) (p <0.0001). Correlations in sex and age adjusted nevus density were higher in MZ pairs (0.94, 95%CI 0.92–0.96) than in DZ pairs (0.61, 95%CI 0.49–0.72), were notably similar to those of the Australian study (MZ = 0.94, DZ = 0.60), and were consistent with high heritability (65% in the U.K., 68% in Australia). We conclude that emergence of nevi in adolescents is under strong genetic control, whereas environmental exposures affect the mean number of nevi.Keywords: genes, heritability, melanoma, nevi, twins
    Journal of Investigative Dermatology 07/2001; 117(2):348-352. DOI:10.1046/j.0022-202x.2001.01415.x · 6.37 Impact Factor