Gruis N A, Sandkuijl L A, Weber J L, van der Zee A, Borgstein A M, Bergman W, Frants R R
MGC-Department of Human Genetics, Leiden University, The Netherlands.
Melanoma Res. 1993 Aug;3(4):271-7.
Familial atypical multiple mole-melanoma (FAMMM) syndrome is characterized by the familial occurrence of malignant melanoma of the skin in combination with multiple atypical precursor naevi. In the present study we performed linkage analysis in seven Dutch FAMMM families to define the relationship between the ultimate phenotype melanoma and the postulated precursors, atypical (dysplastic) naevi. Various models were defined, varying from melanoma only to various combinations of melanoma and atypical naevi, reflecting the FAMMM phenotype. Using 124 microsatellite markers spread across all autosomes, hints for linkage were obtained between several chromosome 9p markers and a melanoma locus (D9S171; odds for linkage, 275:1). In a model including melanoma and a florid manifestation of atypical naevi a considerably higher lod score was obtained with D9S171 (odds for linkage, 4365:1); models including milder manifestations yielded less support. We conclude that, also in the Dutch FAMMM families, a melanoma gene is located on the short arm of chromosome 9 and that multiple atypical naevi, at least in certain cases, seems to be a component of the FAMMM phenotype.
家族性非典型多发性痣-黑色素瘤（FAMMM）综合征的特征是家族性发生皮肤恶性黑色素瘤并伴有多个非典型前体痣。在本研究中，我们对7个荷兰FAMMM家族进行了连锁分析，以确定最终表型黑色素瘤与假定的前体、非典型（发育异常）痣之间的关系。定义了各种模型，从仅黑色素瘤到黑色素瘤与非典型痣的各种组合，反映了FAMMM表型。使用分布在所有常染色体上的124个微卫星标记，在几个9号染色体短臂标记与一个黑色素瘤基因座（D9S171；连锁几率，275:1）之间获得了连锁线索。在一个包括黑色素瘤和非典型痣的明显表现的模型中，D9S171获得了相当高的对数优势分数（连锁几率，4365:1）；包括较轻表现的模型得到的支持较少。我们得出结论，在荷兰FAMMM家族中，一个黑色素瘤基因也位于9号染色体短臂上，并且多个非典型痣至少在某些情况下似乎是FAMMM表型的一个组成部分。
