Sunita M C De Sousa1,2,3, Richard W Carroll4, Alex Henderson5, John Burgess6,7, Roderick J Clifton-Bligh8,9. 1. Endocrine & Metabolic Unit, Royal Adelaide Hospital, Adelaide, SA, Australia. Sunita.DeSousa@sa.gov.au. 2. South Australian Adult Genetics Unit, Royal Adelaide Hospital, Adelaide, SA, Australia. Sunita.DeSousa@sa.gov.au. 3. Adelaide Medical School, University of Adelaide, Adelaide, SA, Australia. Sunita.DeSousa@sa.gov.au. 4. Endocrine, Diabetes, and Research Centre, Wellington Regional Hospital, Wellington, New Zealand. 5. Wellington Hospital, Genetic Health Service New Zealand, Wellington, New Zealand. 6. Department of Diabetes and Endocrinology, Royal Hobart Hospital, Hobart, TAS, Australia. 7. School of Medicine, University of Tasmania, Hobart, TAS, Australia. 8. Department of Endocrinology, Royal North Shore Hospital, Sydney, NSW, Australia. 9. Cancer Genetics Laboratory, Kolling Institute, University of Sydney, Sydney, NSW, Australia.
Abstract
PURPOSE: The improved access and affordability of next generation sequencing has facilitated the clinical use of gene panel testing to test concurrently patients for multiple heritable hyperparathyroidism syndromes. However, there is little guidance as to which patients should be selected for gene panel testing and which genes should be included in such panels. In this review, we provide a practical approach to considering, interpreting and managing genetic testing for familial primary hyperparathyroidism (PHPT) syndromes and familial hypocalciuric hypercalcaemia (FHH) in patients with PTH-dependent hypercalcaemia. We discuss known genes implicated in PHPT and FHH, testing criteria and yields, pre-test counselling, laboratory considerations, and post-test management. METHODS: In addition to reviewing the literature, we conducted audits of local genetic testing data to examine the real-world yield of genetic testing in patients with PTH-dependent hypercalcaemia. RESULTS: Our local audits revealed a positive genetic testing rate of 15-26% in patients with suspected hyperparathyroidism syndromes. CONCLUSION: Based on the particular testing criteria met, affected patients should be tested for variants in the genes currently implicated in PHPT (MEN1, CDC73, RET, CDKN1B, GCM2, CASR) and/or FHH (CASR, GNA11, AP2S1). Patients should be provided with pre- and post-test counselling, including consideration of potential implications for family members.
PURPOSE: The improved access and affordability of next generation sequencing has facilitated the clinical use of gene panel testing to test concurrently patients for multiple heritable hyperparathyroidism syndromes. However, there is little guidance as to which patients should be selected for gene panel testing and which genes should be included in such panels. In this review, we provide a practical approach to considering, interpreting and managing genetic testing for familial primary hyperparathyroidism (PHPT) syndromes and familial hypocalciuric hypercalcaemia (FHH) in patients with PTH-dependent hypercalcaemia. We discuss known genes implicated in PHPT and FHH, testing criteria and yields, pre-test counselling, laboratory considerations, and post-test management. METHODS: In addition to reviewing the literature, we conducted audits of local genetic testing data to examine the real-world yield of genetic testing in patients with PTH-dependent hypercalcaemia. RESULTS: Our local audits revealed a positive genetic testing rate of 15-26% in patients with suspected hyperparathyroidism syndromes. CONCLUSION: Based on the particular testing criteria met, affected patients should be tested for variants in the genes currently implicated in PHPT (MEN1, CDC73, RET, CDKN1B, GCM2, CASR) and/or FHH (CASR, GNA11, AP2S1). Patients should be provided with pre- and post-test counselling, including consideration of potential implications for family members.
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