Because mutations in the gene encoding fumarate hydratase (FH) underlie syndromic forms of uterine leiomyomas, namely multiple cutaneous and uterine leiomyomata (150800), Gross et al. (2004) investigated whether mutations in the FH gene may predispose women to developing ... Because mutations in the gene encoding fumarate hydratase (FH) underlie syndromic forms of uterine leiomyomas, namely multiple cutaneous and uterine leiomyomata (150800), Gross et al. (2004) investigated whether mutations in the FH gene may predispose women to developing nonsyndromic UL. They performed a genetic linkage study with DNA from 123 families containing at least 1 affected sister pair. In addition, to assess the frequency of FH loss specifically in UL with 1q rearrangements, they performed a 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 (p = 0.04). FISH results showed that 1 copy of FH was absent in 9 of 11 ULs. Gross et al. (2004) concluded that loss of FH may be a significant event in the pathogenesis of a subset of nonsyndromic ULs. Makinen et al. (2011) performed whole-exome sequencing on 18 uterine leiomyomas derived from 17 different patients and identified tumor-specific mutations in the MED12 gene in 10. Analysis of 207 additional tumors identified mutations in MED12 (300188), a subunit of the Mediator complex, in 70% (159/225) of tumors from a total of 80 patients. The Mediator complex is a 26-subunit transcriptional regulator that bridges DNA regulatory sequences to the RNA polymerase II initiation complex (see 180660). All mutations identified by Makinen et al. (2011) resided in exon 2, suggesting that aberrant function of this region of MED12 contributes to tumorigenesis.