AP2S1, CASR, CDC73, CDKN1B, MEN1 AND RET GENE ANALYSIS IN FAMILIAL ISOLATED HYPERPARATHYROIDISM
Primary hyperparathyroidism is characterised by hypercalcaemia, inappropriately high parathyroid hormone (PTH) levels and isolated parathyroid tumours. Hereditary primary hyperparathyroidism may develop as a solitary endocrinopathy or as part of the Multiple Endocrine Neoplasia type 1 (MEN1) or hereditary hyperparathyroidism-jaw tumour (HPT-JT) syndromes.
MEN1 disease-causing variants have been reported in 20-57% of families with familial isolated hyperparathyroidism (Villablanca et al 2002 Eur J Endocrinol 147:313-322; Pannett et al 2003 Clin Endocrinol 58:639-646). Inactivating variants of CDC73 (formerly known as HRPT2), account for approximately 14% of familial isolated hyperparathyroidism cases and 50% of HPT-JT cases (Cascon et al 2011 Genes Chromosomes and Cancer 50:922-929). Inactivating variants in the CASR gene cause primary hyperparathyroidism and Familial hypocalciuric hypercalcaemia (FHH). Variants in CASR account for approximately 15-18% of Familial Isolated Hyperparathyroidism cases (Warner et al 2004 J Med Genet 41:155-160).
The laboratory participates in the European Molecular Genetics Quality Network (EMQN) sequencing scheme.
NHSE test directory code: R151 Familial hyperparathyroidism. Testing criteria can be found on this webpage: https://www.england.nhs.uk/publication/national-genomic-test-directories/.
AMEND is a registered charity offering support for patients with MEN types 1 and 2, and associated sporadic growths. Click here to view their website.