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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

Involvement of fumarate hydratase in nonsyndromic uterine leiomyomas: genetic linkage analysis and FISH studies.

Recently, germline mutations of the fumarate hydratase (FH) gene, in 1q42.1, have been found to be involved in syndromes associated with uterine leiomyomas (ULs). Compelling evidence also supports a genetic liability to develop nonsyndromic UL, although susceptibility genes have not been reported to date. Loss of heterozygosity (LOH) studies have found no or rare evidence of LOH of FH in nonsyndromic UL. However, the karyotypes of these tumors were not reported, and cytogenetic aberrations of 1q42-44 have been observed infrequently in UL. To determine whether FH mutations also may predispose women to developing nonsyndromic UL, we performed a genetic linkage study with DNA from 123 families containing at least one affected sister pair. In addition, to assess the frequency of FH loss specifically in UL with 1q rearrangements, we performed a fluorescence in situ hybridization (FISH) analysis of UL with 1q rearrangements. Analysis of the genotyping data revealed evidence suggestive of linkage to the FH region among study participants who were less than 40 years of age at diagnosis (Zlr 1.7 at D1S547, P = 0.04). FISH results showed that one copy of FH was absent in 9 of 11 ULs. These data indicate that loss of FH might be a significant event in the pathogenesis of a subset of nonsyndromic ULs.[1]


  1. Involvement of fumarate hydratase in nonsyndromic uterine leiomyomas: genetic linkage analysis and FISH studies. Gross, K.L., Panhuysen, C.I., Kleinman, M.S., Goldhammer, H., Jones, E.S., Nassery, N., Stewart, E.A., Morton, C.C. Genes Chromosomes Cancer (2004) [Pubmed]
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