Osteogenesis imperfecta

Gene: CASR

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

• 22620673

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.

Red List (low evidence)

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

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.