Hereditary leiomyomatosis and renal cell carcinoma (HLRCC) is a cancer syndrome that is caused by mutations in the FH gene in 90% of cases. In the other 10% of cases, the genetic cause is unknown. Here, the authors examined 28 patients from 13 families where no point mutation in FH has been found. These persons were screened for abnormalities that involve the FH gene. They discover that all 13 families carry deletions of chromosome 1q42, the region where FH is located. Eleven of the families have a full deletion of the FH gene and two families have a partial deletion. All 13 female patients (100%) from 7 different families had uterine leiomyomas. There were no female patients identified in the families with partial deletions so they were unable to determine if the partial deletion could cause uterine leiomyomas. Twenty patients were examined for cutaneous leiomyomas, and 18 of them (90%) were found to have this type of cancer. Cutaneous leiomyomas were found in families with full deletions or with the partial deletions.
Finally, there were 9 patients (from 7 families) with kidney cancer, and it was associated with both the full deletions and the partial deletions. Most individuals (8 of 9) had type-2 papillary renal cell carcinoma, which is common with HLRCC. The percentage of patients presenting with each feature is very similar to what has been described for patients with point mutations in the FH gene. Deletions of 1q42 involving all or part of the FH gene is a genetic basis for HLRCC in the families where no point mutation in the FH gene is found.
Comprehensive genomic and phenotypic characterization of germline FH deletion in hereditary leiomyomatosis and renal cell carcinoma Vocke, CD et al., Genes Chromosomes Cancer. 2017 Jun;56(6):484-492. doi: 10.1002/gcc.22452.