Skeletal dysplasia

Gene: RASGRP2

Green List (high evidence)

Osteopetrosis and related disorders SD gp - 4 cases (3 families) all had increased bone density. Primary feature is bleeding/immdef - gene previously called CalDAG-GEF1.; Review on behalf of Tracy Lester

Created: 6 Mar 2019, 11:44 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Bleeding disorder, platelet-type, 18 615888

Publications

• 18709451
• 24958846

I don't know

PMID: 18709451 - Kilic et al 2009 - 3 families with 4 individuals with Leukocyte adhesion deficiency (LAD) type III (severe recurrent infections, leukocytosis, and increased bleeding tendency). All patients had increased bone density on X-ray similar to that seen in patients with osteopetrosis, and variants in the CalDAG-GEF1 gene (now called RASGRP2). A splice junction mutation was found in families 1 and 3. The patient from family 2 had very low levels of CalDAG-GEF1. . Knock out CalDAG-GEFI deficient mice exhibit the same platelet and neutrophil adhesion defect but NO abnormalities in bone density on X-ray.

PMID: 24958846 - Canault et al 2014 - three siblings affected by severe bleeding - whole-exome sequencing identified the culprit mutation (cG742T) in RASGRP2 - couldn't find any mention of a bone density/skeletal dysplasia phenotype.

Created: 13 May 2019, 1:24 p.m.

This gene was part of an initial gene list collated by Tracy Lester, Oxford Medical Genetics Laboratories, Oxford University Hospitals NHS Foundation Trust, February 2019 on behalf of the GMS Musculoskeletal Specialist Group; Gene symbol submitted: RASGRP2; Initial rating suggestion: green if SD, red if not

Created: 6 Mar 2019, 11:36 a.m.

Comment on publications: 18709451 reports a splice site variant in two apparently unrelated consanguineous families resulting in reduced expression (qPCR)(no HVGS provided), reduced expression was also reported in another consanguineous family (no HVGS provided)

Created: 11 Jul 2016, 7:34 a.m.

Comment on list classification: Used diagnostically by Ana Beleza (Guy's and St Thomas' NHS Foundation Trust)

Created: 21 Jun 2016, 1:08 p.m.

Green List (high evidence)

Tier 2

Created: 17 Jun 2016, 8:07 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
?Bleeding disorder, platelet-type, 18 615888; Osteopetrosis - Kilic SS et al. The clinical spectrum of leukocyte adhesion deficiency (LAD) III due to defective CalDAG-GEF1. J Clin Immunol. 2009 Jan, 29(1):117-22.

Variants in this GENE are reported as part of current diagnostic practice