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Fumarate hydratase mutations and predisposition to cutaneous leiomyomas, uterine leiomyomas and renal cancer.
Br J Dermatol. 2005 Jul; 153(1):11-7.BJ

Abstract

Germline heterozygous loss-of-function mutations of fumarate hydratase (FH) predispose to the autosomal dominant syndrome of multiple cutaneous and uterine leiomyomatosis (MCUL). Forty-five distinct FH mutations have been identified in 76 of 89 (85%) reported probands with skin leiomyomas. This suggests that MCUL is a genetically homogeneous condition and that most patients presenting with skin leiomyomas will have underlying FH mutations. FH mutations identified include 26/45 (58%) missense; 12/45 (27%) frameshift, 4/45 (9%) nonsense changes and 3/45 (7%) different whole gene deletions. In MCUL kindreds, the majority of females with FH mutations have both skin and uterine leiomyomas. A proportion of individuals with FH mutations have associated renal cancer, a variant known as hereditary leiomyomatosis and renal cell cancer (HLRCC). If selection bias is removed, the prevalence of renal cancer in MCUL lies between one of 46 (2%) families who were not radiologically screened, and two of 32 (6%) families who were radiologically screened. Truncating, particularly frameshift, mutations appear to be significantly associated with renal cancer (P = 0.003), suggesting a possible basis for selective screening. There may also be a significantly increased rate of renal cancer in females (P = 0.004), suggesting a possible role for hormonal factors. Review of the literature suggests that, unlike most individuals presenting with skin leiomyomas, the majority of patients presenting with uterine leiomyomas or renal cancer will not have underlying FH mutations.

Authors+Show Affiliations

Molecular and Population Genetics Laboratory, Cancer Research UK, Lincoln's Inn Fields, London WC2A 3PX, UK. ufrina.alam@gmail.comNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Review

Language

eng

PubMed ID

16029320

Citation

Alam, N A., et al. "Fumarate Hydratase Mutations and Predisposition to Cutaneous Leiomyomas, Uterine Leiomyomas and Renal Cancer." The British Journal of Dermatology, vol. 153, no. 1, 2005, pp. 11-7.
Alam NA, Olpin S, Leigh IM. Fumarate hydratase mutations and predisposition to cutaneous leiomyomas, uterine leiomyomas and renal cancer. Br J Dermatol. 2005;153(1):11-7.
Alam, N. A., Olpin, S., & Leigh, I. M. (2005). Fumarate hydratase mutations and predisposition to cutaneous leiomyomas, uterine leiomyomas and renal cancer. The British Journal of Dermatology, 153(1), 11-7.
Alam NA, Olpin S, Leigh IM. Fumarate Hydratase Mutations and Predisposition to Cutaneous Leiomyomas, Uterine Leiomyomas and Renal Cancer. Br J Dermatol. 2005;153(1):11-7. PubMed PMID: 16029320.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Fumarate hydratase mutations and predisposition to cutaneous leiomyomas, uterine leiomyomas and renal cancer. AU - Alam,N A, AU - Olpin,S, AU - Leigh,I M, PY - 2005/7/21/pubmed PY - 2005/10/26/medline PY - 2005/7/21/entrez SP - 11 EP - 7 JF - The British journal of dermatology JO - Br J Dermatol VL - 153 IS - 1 N2 - Germline heterozygous loss-of-function mutations of fumarate hydratase (FH) predispose to the autosomal dominant syndrome of multiple cutaneous and uterine leiomyomatosis (MCUL). Forty-five distinct FH mutations have been identified in 76 of 89 (85%) reported probands with skin leiomyomas. This suggests that MCUL is a genetically homogeneous condition and that most patients presenting with skin leiomyomas will have underlying FH mutations. FH mutations identified include 26/45 (58%) missense; 12/45 (27%) frameshift, 4/45 (9%) nonsense changes and 3/45 (7%) different whole gene deletions. In MCUL kindreds, the majority of females with FH mutations have both skin and uterine leiomyomas. A proportion of individuals with FH mutations have associated renal cancer, a variant known as hereditary leiomyomatosis and renal cell cancer (HLRCC). If selection bias is removed, the prevalence of renal cancer in MCUL lies between one of 46 (2%) families who were not radiologically screened, and two of 32 (6%) families who were radiologically screened. Truncating, particularly frameshift, mutations appear to be significantly associated with renal cancer (P = 0.003), suggesting a possible basis for selective screening. There may also be a significantly increased rate of renal cancer in females (P = 0.004), suggesting a possible role for hormonal factors. Review of the literature suggests that, unlike most individuals presenting with skin leiomyomas, the majority of patients presenting with uterine leiomyomas or renal cancer will not have underlying FH mutations. SN - 0007-0963 UR - https://www.unboundmedicine.com/medline/citation/16029320/Fumarate_hydratase_mutations_and_predisposition_to_cutaneous_leiomyomas_uterine_leiomyomas_and_renal_cancer_ L2 - https://doi.org/10.1111/j.1365-2133.2005.06678.x DB - PRIME DP - Unbound Medicine ER -