Familial hyperparathyroidism or hypocalciuric hypercalcaemia
Gene: AP2S1Additional evidence from mouse model that is representative for FHH3 in humans:
PMID: 33729479 - Hannan et al 2021 - Created mice with the AP2S1 p.Arg15Leu mutation, which causes the most severe FHH3 phenotype. Heterozygous (Ap2s1+/L15) mice were viable, homozygous mice died perinatally, The heterozygous mice showed hypercalcaemia, hypermagnesaemia, hypophosphataemia. The phenotype can be ameliorated by treatment with cinacalcet.Created: 8 Mar 2022, 3:36 p.m. | Last Modified: 8 Mar 2022, 3:36 p.m.
Panel Version: 2.16
Phenotypes
Hypocalciuric hypercalcemia, type III, OMIM:600740
Publications
Submitted on behalf of Treen Cranston (Oxford): codon 15 should be covered.Created: 31 Jul 2019, 2:14 p.m. | Last Modified: 31 Jul 2019, 2:14 p.m.
Panel Version: 1.3
As discussed in the GMS Endocrinology Specialist Test Group webex call 28th Jan 2019: The Specialist Test Group agreed that there is enough evidence to rate this gene green.Created: 29 Jan 2019, 11:51 a.m.
Comment on list classification: Have given AP2S1 a green gene status as recommended by Treena Cranston's (Oxford) review.Created: 11 Jan 2019, 9:12 a.m.
pathogenic mutations affecting codon 15 of AP2S1 are causative of FHH3. There can be clinical overlap between hyperparathyroidism and FHH and as such AP2S1, which is a simple test should be considered as part of the differential diagnosis. In our own cohort of individuals referred for the hyperparathyroidism panel we have detected 2 individuals with pathogenic AP2S1 variants (unpublished).
Due to clinical overlap and clinical management of the different conditions, Inclusion of the FHH genes on hyperparathyroidism gene panel lists is a recommendation from an international workshop: Diagnosis of Asymptomatic Primary Hyperparathyroidism: Proceedings of the Fourth International Workshop PMID: 25162666
Sources: Expert ReviewCreated: 9 Jan 2019, 6:07 p.m.
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes
FHH3
Publications
Variants in this GENE are reported as part of current diagnostic practice
Publications for gene: AP2S1 were set to 25162666; 28740527; 26963950
Phenotypes for gene: AP2S1 were changed from Hypocalciuric hypercalcemia, type III, 600740 to Hypocalciuric hypercalcemia, type III, OMIM:600740
Treena Cranston: pathogenic mutations affecting
Gene: ap2s1 has been classified as Green List (High Evidence).
Gene: ap2s1 has been classified as Green List (High Evidence).
Publications for gene: AP2S1 were set to PMID: 25162666; PMID: 28740527
Phenotypes for gene: AP2S1 were changed from FHH3; Hypocalciuric hypercalcemia, type III, 600740 to Hypocalciuric hypercalcemia, type III, 600740
Mode of inheritance for gene: AP2S1 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes for gene: AP2S1 were changed from FHH3 to FHH3; Hypocalciuric hypercalcemia, type III, 600740
gene: AP2S1 was added gene: AP2S1 was added to Familial hyperparathyroidism. Sources: Expert Review Mode of inheritance for gene: AP2S1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: AP2S1 were set to PMID: 25162666; PMID: 28740527 Phenotypes for gene: AP2S1 were set to FHH3 Penetrance for gene: AP2S1 were set to unknown gene: AP2S1 was marked as current diagnostic