Genes in panel
STRs in panel
Prev Next
Regions in panel
Prev Next

Osteogenesis imperfecta

Gene: CASR

Green List (high evidence)

CASR (calcium sensing receptor)
EnsemblGeneIds (GRCh38): ENSG00000036828
EnsemblGeneIds (GRCh37): ENSG00000036828
OMIM: 601199, Gene2Phenotype
CASR is in 14 panels

5 reviews

Duncan Baker (Sheffield Genetics)

Green List (high evidence)

Affects neonates, fractures are a feature.
Created: 3 Apr 2019, 4:14 p.m.

Phenotypes
neonatal severe hyperparathyroidism 239200; severe hypercalcemia, bone demineralization, multiple fractures

Publications

Eleanor Williams (Genomics England Curator)

I don't know

Comment on list classification: This gene was discussed in the GMS musculoskeletal specialist test group Webex on 2019-06-04. It was decided that due to further evidence, it should be made green.
Created: 11 Jun 2019, 3:20 p.m.
This gene was discussed in the GMS musculoskeletal specialist test group Webex on 2019-06-04. It was decided that due to further evidence, it should be made green.
Created: 11 Jun 2019, 2:08 p.m.
Associated with Hyperparathyroidism, neonatal, Hypocalcemia, autosomal dominant, Hypocalcemia, autosomal dominant, with Bartter syndrome and Hypocalciuric hypercalcemia, type I in OMIM.

Multiple fractures is listed as one of the clinical phenotypes for Hyperparathyroidism, neonatal in OMIM.

PMID: 22620673 - Tonyushkina et al 2012 - report a case of an unusually severe neonatal Familial Hypocalciuric Hypercalcemia due to a novel CaSR gene mutation that presented with perinatal fractures and moderate hypercalcemia. A heterozygous nucleotide substitution c.1664 T>C in exon 6, resulting in an amino acid change I555T.

PMID: 30376845 - Capozza et al 2018 - report a case of a child with Neonatal severe primary hyperparathyroidism. Phenotype included fracture of the humerus neck and severe osteoporosis. The patient was found to have a homozygous novel mutation of the splicing donor site of the intron 5 ( c.1608 + 1G > A –IVS5 + 1G > A. Both asymptomatic parents were found to be heterozygous.

PMID: 26161261 - Fisher et al 2015 - report two unrelated patients with neonatal severe hyperparathyroidism and de novo R185Q heterozygous inactivating CASR mutations. Patient 2 had multiple rib fractures.

Summary: 3 cases reported of patients with variants in CASR and neonatal severe hyperparathyroidism or severe neonatal Familial Hypocalciuric Hypercalcemia. Patients homo- and hetero-zygous for variants in CASR are reported.
Created: 11 Jun 2019, 2:07 p.m.
This gene was part of an initial gene list collated by Duncan Baker, Sheffield Diagnostic Genetics Service, January 2019 on behalf of the GMS Musculoskeletal Specialist Group; Gene symbol submitted: CASR; Suggested initial gene rating: green
Created: 3 Apr 2019, 4:08 p.m.

Meena Balasubramanian (Sheffield Children's NHS Foundation Trust)

Red List (low evidence)

Rebecca Pollitt (Sheffield Diagnostic Genetics Service ; University of Sheffield)

Red List (low evidence)

Mode of inheritance
BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal

Phenotypes
familial hypocalciuric hypercalcemia; neonatal severe hyperparathyroidism

Christine Burren (University Hospitals Bristol NHS Foundation Trust)

Red List (low evidence)

This gene is associated with Autosomal Dominant Hypocalc Hypercalcuria Syndromes as opposed to the Osteogenesis Imperfecta phenotype.
Created: 14 Dec 2015, 10:10 a.m.

Details

Mode of Inheritance
BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Sources
  • Expert Review Green
  • NHS GMS
  • Emory Genetics Laboratory
Phenotypes
  • Osteogenesis Imperfecta and Decreased Bone Density
  • skeletal dysplasias
  • neonatal severe hyperparathyroidism 239200
  • severe hypercalcemia, bone demineralization, multiple fractures
  • familial hypocalciuric hypercalcemia
OMIM
601199
Clinvar variants
Variants in CASR
Penetrance
Complete
Publications
Panels with this gene

History Filter Activity

11 Jun 2019, Gel status: 3

Entity classified by Genomics England curator

Eleanor Williams (Genomics England Curator)

Gene: casr has been classified as Green List (High Evidence).

11 Jun 2019, Gel status: 1

Set mode of inheritance

Eleanor Williams (Genomics England Curator)

Mode of inheritance for gene: CASR was changed from to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal

15 May 2019, Gel status: 1

Set Phenotypes

Eleanor Williams (Genomics England Curator)

Phenotypes for gene: CASR were changed from Osteogenesis Imperfecta and Decreased Bone Density; skeletal dysplasias to Osteogenesis Imperfecta and Decreased Bone Density; skeletal dysplasias; neonatal severe hyperparathyroidism 239200; severe hypercalcemia, bone demineralization, multiple fractures; familial hypocalciuric hypercalcemia

15 May 2019, Gel status: 1

Set publications

Eleanor Williams (Genomics England Curator)

Publications for gene: CASR were set to

13 Mar 2019, Gel status: 1

Added New Source

Eleanor Williams (Genomics England Curator)

Source NHS GMS was added to CASR.

10 May 2016, Gel status: 1

Gene classified by Genomics England curator

Chris Boustred (Genomics England)

This gene has been classified as Red List (Low Evidence).

23 Jun 2015, Gel status: 1

Added New Source

Ellen McDonagh (Genomics England Curator)

CASR was added to Osteogenesis Imperfecta panel. Sources: Emory Genetics Laboratory