| Entity | Uterine Leiomyomata (UL) |
| Note | Synonyms include uterine fibroids, fibromas, myofibromas and myomas. |
| Disease | Benign mesenchymal tumors of the uterus. |
| Prognosis | Excellent, but may require surgical intervention as one- third of hysterectomies performed in the United States have a primary indication of UL. |
| Cytogenetics | UL rarely associated with cytologically visible 1q42 deletions. |
| Hybrid/Mutated Gene | Deletions of FH from structural rearrangements of 1q42.1. |
| Abnormal Protein | Presumed haploinsufficiency or functional null if mutation in other FH allele occurs. |
| | |
| Entity | Hereditary leiomyomatosis and renal cell carcinoma (HLRCC)/ multiple cutaneous and uterine leiomyomatosis (MCUL1). |
| Note | Also known as Reed¹s syndrome. |
| Disease | HLRCC is an autosomal dominant disorder, characterized by smooth muscle tumors of the skin and uterus and/or kidney. |
| Prognosis | Good, if early diagnosis. |
| Abnormal Protein | Inherited mutations can predispose to somatic deletions resulting in truncated, non-functional or absent proteins. |
| Oncogenesis | FH acts as classic tumor suppressor gene in HLRCC/MCUL1. Genetic or epigenetic alterations in FH resulting from substitution, deletion or methylation follow the Knudson ³two hit² mechanism. The resulting functionally null state for fumarase can lead to subsequent oxidative tissue damage and tumorigenesis. |
| | |
| Entity | Fumarate hydratase deficiency (FHD). |
| Note | Synonymous with fumarase deficiency and fumaric aciduria. |
| Disease | Autosomal recessive condition characterized by delayed development, diminished muscle tone, and encephalopathy likely due to limited energy generation during development. |
| Prognosis | Poor. FHD is a rare condition, but reported cases indicate most affected individuals survive only several months while very few survive into their third decade. |
| Hybrid/Mutated Gene | The most common allelic abnormality is a 3 base pair- AAA insertion. |
| Abnormal Protein | Mutations near fumarase active site result in absent or truncated protein. |
| | |
| Mitochondrial and cytoplasmic fumarases in Saccharomyces cerevisiae are encoded by a single nuclear gene FUM1. |
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