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, and select noncoding variants. Our assay provides a Q30 quality-adjusted mean coverage depth of 350x (50x minimum, or supplemented with additional analysis). Variants classified as pathogenic or likely pathogenic are confirmed with orthogonal methods, except individual variants that have high quality scores and previously validated in at least ten unrelated samples.
Our analysis detects most intragenic deletions and duplications at single exon resolution. However, in rare situations, single-exon copy number events may not be analyzed due to inherent sequence properties or isolated reduction in data quality. If you are requesting the detection of a specific single-exon copy number variation, please contact Client Services before placing your order.
|Gene||Transcript reference||Sequencing analysis||Deletion/Duplication analysis|