Alam N A, Bevan S, Churchman M, Barclay E, Barker K, Jaeger E E, Nelson H M, Healy E, Pembroke A C, Friedmann P S, Dalziel K, Calonje E, Anderson J, August P J, Davies M G, Felix R, Munro C S, Murdoch M, Rendall J, Kennedy S, Leigh I M, Kelsell D P, Tomlinson I P, Houlston R S
Molecular and Population Genetics Laboratory and Skin Tumour Laboratory, Imperial Cancer Research Fund, Royal London Hospital, London, United Kingdom.
Am J Hum Genet. 2001 May;68(5):1264-9. doi: 10.1086/320124. Epub 2001 Mar 14.
Dominant transmission of multiple uterine and cutaneous smooth-muscle tumors is seen in the disorder multiple leiomyomatosis (ML). We undertook a genomewide screen of 11 families segregating ML and found evidence for linkage to chromosome 1q42.3-q43 (maximum multipoint LOD score 5.40). Haplotype construction and analysis of recombinations permitted the minimal interval containing the locus, which we have designated "MCUL1," to be refined to an approximately 14-cM region flanked by markers D1S517 and D1S2842. Allelic-loss studies of tumors indicated that MCUL1 may act as a tumor suppressor. Identification of MCUL1 should have wide interest, since this gene may harbor low-penetrance variants predisposing to the common form of uterine fibroids and/or may undergo somatic mutation in sporadic leiomyomata.
在多发性平滑肌瘤病(ML)中可见多个子宫和皮肤平滑肌肿瘤的显性遗传。我们对11个患ML的家系进行了全基因组筛查,发现与1号染色体1q42.3 - q43连锁的证据(最大多点对数优势计分5.40)。单倍型构建和重组分析确定了包含该位点的最小区间,我们将其命名为“MCUL1”,该区间被精确定位到由标记D1S517和D1S2842侧翼的约14厘摩区域。肿瘤的等位基因缺失研究表明,MCUL1可能作为一种肿瘤抑制因子发挥作用。MCUL1的鉴定应会引起广泛关注,因为该基因可能携带易患常见类型子宫肌瘤的低外显率变异,和/或可能在散发性平滑肌瘤中发生体细胞突变。