Osteogenesis imperfecta

Gene: GORAB

I don't know

Comment on list classification: Following discussion in the GMS musculoskeletal specialist test group Webex on 2019-06-04 it was decided to rate this gene green. Sufficient cases.

Created: 11 Jun 2019, 2:53 p.m.

PMID: 18997784 - Hennies et al 2008 - Gene is called by previous name of SCYL1BP1. Looked at 13 families all showing the typical GO phenotype. A homozygous nonsense mutation, p.E123X, in the gene SCYL1BP1 (in all affected individuals from all 4 Mennonite families - likely founder effect. In 9 additional GO patients from Germany, Italy, Oman, Pakistan, Libya, Mexico, and the U.S. they found eight other mutations, including five nonsense mutations, two frameshift mutations, one splice site mutation, and one mutation of the deduced methionine start codon.

PMID: 28807865 - Takeda et al 2017 - in 1 patient with Geroderma osteodysplastica with two novel compound heterozygous nonsense mutations in the GORAB gene.

Created: 15 May 2019, 3:45 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: GORAB; Suggested initial gene rating: green

Created: 3 Apr 2019, 4:08 p.m.

Green List (high evidence)

Following discussion with Dr Balasubramanian - rate green

Created: 3 Apr 2019, 4:14 p.m.

PMID: 28807865 Patient with recurrent long bone fractures and clinical features, including wrinkled skin, joint laxity, and a distinctive face, low bone mineral density. Whole exome sequencing revealed two novel compound heterozygous nonsense mutations in the GORAB gene (p.Arg60* and p.Gln124*).
PMID: 18997784 Found a homozygous nonsense mutation in the GORAB gene in 12 affected individuals from 4 Mennonite pedigrees with geroderma osteodysplastica.

Created: 22 Jan 2019, 11:52 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
congenital wrinkly skin; prematurely aged face; extremely short stature; osteoporosis leading to recurrent fractures

Publications

• 18997784
• 28807865

Red List (low evidence)

Red List (low evidence)