This test analyzes the FH gene associated with hereditary leiomyomatosis and renal cell cancer (HLRCC). HLRCC is characterized by cutaneous leiomyomas, uterine leiomyomas, and/or renal tumors. Individuals with HLRCC are also at risk of having a child with autosomal recessive fumarate hydratase deficiency (FHD) if their partner also carries an FH pathogenic variant.
Genetic testing of this gene may confirm a diagnosis and help guide treatment and management decisions. Identification of a disease-causing variant would also guide testing and diagnosis of at-risk relatives. This test is specifically designed for heritable germline mutations and is not appropriate for the detection of somatic mutations in tumor tissue.
Hereditary leiomyomatosis and renal cell cancer (HLRCC) is characterized by cutaneous leiomyomas, uterine leiomyomas, and renal tumors. Affected individuals typically have multiple cutaneous leiomyomas on the abdomen, shoulders and extremities, which typically manifest in the second to fourth decade of life. Uterine leiomyomas (fibroids or “smooth muscle tumors”) are present in nearly all women with HLRCC. Uterine leiomyomas cause pelvic pain and irregular or heavy menstruation but rarely become cancerous.
Renal tumors, which may be either unifocal or unilateral, occur in approximately 15% of affected individuals. Several tumor types have been reported, including type 2 papillary renal cell carcinoma, collecting-duct carcinomas and Wilms tumor.
HLRCC is inherited in an autosomal dominant pattern. Most cases are inherited and the rate of spontaneous de novo mutations is unknown. Fumarate hydratase deficiency (FHD) has autosomal recessive inheritance.
HLRCC is very rare. More than 200 cases have been described, but the exact prevalence is unknown.
Testing for HLRCC may be considered in individuals with a personal and/or family history of at least one of the following:
For management recommendations, please refer to:
Invitae is a College of American Pathologists (CAP)-accredited and Clinical Laboratory Improvement Amendments (CLIA)-certified clinical diagnostic laboratory performing full-gene sequencing and deletion/duplication analysis using next-generation sequencing technology (NGS).
Our sequence analysis covers clinically important regions of each gene, including coding exons, +/- 10 base pairs of adjacent intronic sequence in the transcript listed below. In addition, analysis covers the select non-coding variants specifically defined in the table below. Any variants that fall outside these regions are not analyzed. Any specific limitations in the analysis of these genes are also listed in the table below.
Based on validation study results, this assay achieves >99% analytical sensitivity and specificity for single nucleotide variants, insertions and deletions <15bp in length, and exon-level deletions and duplications. Invitae's methods also detect insertions and deletions larger than 15bp but smaller than a full exon but sensitivity for these may be marginally reduced. Invitae’s deletion/duplication analysis determines copy number at a single exon resolution at virtually all targeted exons. However, in rare situations, single-exon copy number events may not be analyzed due to inherent sequence properties or isolated reduction in data quality. Certain types of variants, such as structural rearrangements (e.g. inversions, gene conversion events, translocations, etc.) or variants embedded in sequence with complex architecture (e.g. short tandem repeats or segmental duplications), may not be detected. Additionally, it may not be possible to fully resolve certain details about variants, such as mosaicism, phasing, or mapping ambiguity. Unless explicitly guaranteed, sequence changes in the promoter, non-coding exons, and other non-coding regions are not covered by this assay. Please consult the test definition on our website for details regarding regions or types of variants that are covered or excluded for this test. This report reflects the analysis of an extracted genomic DNA sample. In very rare cases, (circulating hematolymphoid neoplasm, bone marrow transplant, recent blood transfusion) the analyzed DNA may not represent the patient's constitutional genome.
|Gene||Transcript reference||Sequencing analysis||Deletion/Duplication analysis|