Familial hyperparathyroidism or hypocalciuric hypercalcaemia
Gene: CDKN1A
CDKN1A 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, 6:24 p.m.
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Variants in this GENE are reported as part of current diagnostic practice
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, 10:18 a.m. | Last Modified: 29 Jan 2021, 10:21 a.m.
Panel Version: 2.8
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. 1 case had CDKN1A R67L, who had primary HPT with a family history of HPT.
PMID: 23715670. 85 parathyroid adenomas from 85 cases were screened. 2 adenomas had CDKN1A variants (c.350G>A p.C117Y and c.26G>A p.R9H). Both cases have no family history of primary hyperparathyroidism (one germline and one of undetermined germline status).
PMID: 30536424. 121 patients were screened. A single CKDN1A VUS was identified (c.350G > A p.(Cys117Tyr)). The authors have deemed this variant likely benign based on gnomAD frequency of near 1 in 500 and reported as a VUS on ClinVar. This variant was also identified in PMID: 23715670.Created: 29 Jan 2021, 10:14 a.m. | Last Modified: 29 Jan 2021, 10:14 a.m.
Panel Version: 2.7
CDKN1A is not confirmed to be associated to multiple endocrine neoplasia 1 on OMIM or Gene2Phenotype. There is only one reported case of a patient with Multiple endocrine neoplasia 1-like disease with a variant in CDKN1A.Created: 5 Dec 2018, 2:33 p.m.
Tag watchlist tag was added to gene: CDKN1A.
Gene: cdkn1a has been classified as Amber List (Moderate Evidence).
Publications for gene: CDKN1A were set to 19141585
Ivone Leong: CDKN1A is not confirmed to be
Gene: cdkn1a has been classified as Red List (Low Evidence).
Publications for gene: CDKN1A were set to
Phenotypes for gene: CDKN1A were changed from No OMIM number to No OMIM number; Multiple endocrine neoplasia 1
gene: CDKN1A was added gene: CDKN1A was added to Familial hyperparathyroidism. Sources: UKGTN Mode of inheritance for gene: CDKN1A was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Phenotypes for gene: CDKN1A were set to No OMIM number