Skeletal dysplasia

Gene: RAB33B

Green List (high evidence)

spondylo-epi-(meta)-physeal dysplasias gp of SD. >3 cases; Review on behalf of Tracy Lester

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

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Smith-McCort dysplasia 2 615222

I don't know

Comment on list classification: 5 cases reported.

Created: 17 Jul 2019, 1:04 p.m. | Last Modified: 17 Jul 2019, 1:04 p.m.

Panel Version: 1.184

Associated with Smith-McCort dysplasia 2 (615222) in OMIM.

PMID: 22652534 - Alshammari et al. (2012) - 1 family - a consanguineous Saudi family segregating Smith-McCort syndrome. Identified a homozygous missense mutation in the RAB33B gene (K46Q). Immunoblot analysis showed severe deficiency of RAB33B in patient cells compared with control cells, and patient fibroblasts also displayed a marked reduction in the immunofluorescence signal corresponding to RAB33B but comparable signal intensity to the Golgi marker giantin.

PMID: 16470731/23042644 - Neumann et al. (2006)/Dupuis et al. (2013) - 1 case. 22-year-old Turkish man with Smith-McCort syndrome-2. Identified a homozygous missense mutation in the RAB33B gene (N148K;). By Western blot analysis and immunofluorescence studies, Dupuis et al. (2013) found marked reduction of the RAB33B protein.

PMID: 28127940 - Salian et al. (2017) - 3 families. 3 SMC patients with four novel pathogenic variants in RAB33B, including homozygosity for c.211C>T (p.R71*), homozygosity for c.365T>C (p.F122S), and compound heterozygosity for c.48delCGGGGCAG (p.G17Vfs*58) and c.490C>T (p.Q164*). The mutations segregated with the disorder in each family. Skeletal survey of all three patients showed predominant abnormalities of the spine and pelvic bones, mildly affected epi‐metaphyses of the long bones, and brachydactyly.

5 cases in total.

Created: 8 May 2019, 3:17 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: RAB33B; Initial rating suggestion: green

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

Comment when marking as ready: Associated with phenotype in OMIM . At least two variants reported

Created: 29 Jul 2016, 1:40 p.m.

Green List (high evidence)

Tier 1

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

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Smith-McCort dysplasia 2 615222

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