Familial hyperparathyroidism or hypocalciuric hypercalcaemia

Gene: CDKN2B

Red List (low evidence)

CDKN2B was published by Agarwal et al, 2009 as potentially implicated in hyperparathyroidism, as such laboratories added it to their testing panels as it is a simple test. However, there has been little corroborating literature since then and in our own hands we have not identified any clearly pathogenic variants. I feel removal from routine panel testing would be appropriate due to difficulties in interpretation/clear association. It may be worth considering in research setting.

Created: 9 Jan 2019, 6:26 p.m.

Variants in this GENE are reported as part of current diagnostic practice

Red List (low evidence)

Comment on list classification: This gene has been proposed to have Green status by Soo-Mi Park (East Anglian Medical Genetics Service).

This gene is not associated with any phenotypes in OMIM or Gene2Phenotype.

Based on the currently available information there does not appear to be enough evidence to support a gene-disease association. Until more evidence is available this gene has been promoted from Red to Amber.

Created: 29 Jan 2021, 10:35 a.m. | Last Modified: 29 Jan 2021, 10:35 a.m.

Panel Version: 2.11

Comment on publications: PMID: 19141585 is study looking at cases of MEN1 or related states for germline mutations in all cyclin-dependent kinase inhibitor (CDKI) genes. 196 cases were tested. 2 case had CDKN2B N41D and L64R. Both cases had primary HPT and there is no family history of the phenotype.

PMID: 23715670. 85 parathyroid adenomas from 85 cases were screened. 1 adenoma had a CDKN2B variant (c.256G>A, Asp86Asn). There was no family history of primary hyperparathyroidism and variant was confirmed in the germline.

PMID: 30536424. 121 patients were screened. No variants were found in CDKN2B.

Created: 29 Jan 2021, 10:34 a.m. | Last Modified: 29 Jan 2021, 10:34 a.m.

Panel Version: 2.9

CDKN2B is not confirmed to be associated with any phenotypes on OMIM or Gene2Phenotype. There are only two reported cases of a patient with Multiple endocrine neoplasia 1-like disease with a variant in CDKN2B.

Created: 5 Dec 2018, 2:33 p.m.