Osteogenesis imperfecta
Gene: CASR
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
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: greenCreated: 3 Apr 2019, 4:08 p.m.
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
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.
Gene: casr has been classified as Green List (High Evidence).
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
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
Publications for gene: CASR were set to
Source NHS GMS was added to CASR.
This gene has been classified as Red List (Low Evidence).
CASR was added to Osteogenesis Imperfecta panel. Sources: Emory Genetics Laboratory