This test analyzes the CDC73 gene, which is associated with the spectrum of CDC73-related disorders including parathyroid carcinoma, familial isolated hyperparathyroidism (FIHP), and hyperparathyroidism-jaw tumor (HPT-JT) syndrome. HPT-JT is characterized by primary hyperthyroidism that is most often due to a benign pituitary adenoma or pituitary hyperplasia, ossifying jaw fibromas, and renal and uterine lesions.
It is important to confirm a diagnosis of HPT-JT because this condition is associated with increased risk of parathyroid and other cancers. Although many of the typical signs and symptoms of HPT-JT evolve with age, genetic testing by analysis of CDC73 may confirm a diagnosis in early childhood 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.
CDC73-related conditions are on clinical spectrum inclusive of familial isolated hyperparathyroidism (FIHP), parathyroid carcinoma, and hyperparathyroidism-jaw tumor (HPT-JT) syndrome. While FIHP and hereditary parathyroid carcinoma lack additional extra-organ involvement, HPT-JT is typically a multi-systemic neoplastic condition. Features include:
While not everyone with a CDC73 pathogenic variant will manifest symptoms, approximately 70% will develop a CDC73-related condition.
In HPT-JT, the onset of primary hyperparathyroidism (PHPT) is typically during adolescence or early adulthood; 80% of cases will develop PHPT by age 40. The risk of parathyroid carcinoma is 10%-15% and there is a 25%-50% risk of developing ossifying jaw fibromas. Approximately 20% of affected individuals develop renal cysts, hamartomas, and more rarely, Wilms tumor; however, the lifetime risk of kidney cancer is currently unclear. Up to 75% of affected females will develop benign or malignant uterine tumors.
The frequency of CDC73 pathogenic variants in individuals with ossifying jaw fibromas is currently unknown; however, an identifiable pathogenic variant is identified in:
Autosomal dominant. Most cases are inherited; the rate of spontaneous de novo mutations is unknown.
The prevalence of CDC73 conditions is currently unknown and appears to be rare.
Analysis of the CDC73 gene may be considered in individuals with the following:
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|