General information
The SALSA MLPA Probemix P466 CDC73 is a research use only (RUO) assay for the detection of deletions or duplications in the CDC73 gene, which is associated with hyperparathyroidism-jaw tumour syndrome (HPT-JT), familial isolated hyperparathyroidism (FIHP) and parathyroid carcinoma.

Germ line inactivating point mutations and deletions of the CDC73 gene (also known as HRTP2) underlie HPT-JT (OMIM: 145001), and CDC73 aberrations are also detected in familial primary hyperparathyroidism (OMIM: 145000). HPT-TJ is an autosomal dominant syndrome, characterized by the predisposition to develop parathyroid adenoma or carcinoma, and by the prevalence to develop malignant neoplastic lesions also in jaw bones, kidneys or uterus. Defects in the tumour suppressor gene CDC73 on chromosome 1q, are identified in approximately 60% of HPT-JT cases (Carpten et al. 2002), and are represented by both intragenic and gross germline deletions of CDC73 (Cascon et al. 2011; Bricaire et al. 2013; Korpi-Hyövälti et al. 2014; Muscarella et al. 2018; Le Collen et al. 2021). Moreover, bi-allelic inactivation or mutations of CDC73 leading to dysfunction of the parafibromin protein have been reported in the majority of sporadic parathyroid carcinomas and also in subsets of parathyroid adenomas (Shattuck et al. 2003; Howell et al. 2003).

More information is available at https://www.ncbi.nlm.nih.gov/books/NBK3789/

This SALSA MLPA probemix is not CE/FDA registered for use in diagnostic procedures. Purchase of this product includes a limited license for research purposes.

Probemix content
The SALSA MLPA Probemix P466-A1 CDC73 contains 38 MLPA probes with amplification products between 124 and 409 nucleotides (nt). This includes 18 probes for the CDC73 gene. Furthermore, this probemix also contains one probe for the B3GALT2 gene that is located in intron 10 of the CDC73 gene, and five probes for flanking regions of the CDC73 gene to aid in the determination of the extent of the possible copy number aberration. In addition, 14 reference probes are included that target relatively copy number stable regions in various cancer types including tumours of the parathyroid gland. Complete probe sequences and the identity of the genes detected by the reference probes are available in Table 3 of the Product Description and online (www.mrcholland.com).

This probemix contains nine quality control fragments generating amplification products between 64 and 105 nt: four DNA Quantity fragments (Q-fragments), two DNA Denaturation fragments (D-fragments), one Benchmark fragment, and one chromosome X and one chromosome Y-specific fragment. More information on how to interpret observations on these control fragments can be found in the MLPA General Protocol and online at www.mrcholland.com.