Skeletal dysplasia

Gene: DDRGK1

Comment when marking as ready: RNA and protein studies performed for the splice variant. These two variants likely represents founder variants

Created: 18 Aug 2023, 12:16 a.m. | Last Modified: 18 Aug 2023, 12:16 a.m.

Panel Version: 0.243

Green List (high evidence)

Comment on gene classification: This gene should be rated GREEN as it has been associated with Spondyloepimetaphyseal dysplasia, Shohat type from seven unrelated cases from multiple ethnicities and supported by functional studies.

PMID:28263186 reported six individuals from three different families of Iraqi Jewish descent (three patients from family 1 and one individual each from families 2-4) identified with homozygous c.408+1G>A donor splice site loss-of-function mutation in DDRGK1 and presented with Shohat-type spondyloepimetaphyseal dysplasia (SEMD). It is a skeletal dysplasia that affects cartilage development.

PMID: 35670300 reported two unrelated cases of Moroccan descent identified with homozygous missense variant c.406G>A and presented with SEMD. PMID:36243336 reported an Omani female patient identified with the same homozygous variant as the Iraqi cases and was reported with SEMD.

In addition, studies on both zebrafish and mouse models confirms the physiological role of DDRGK1 in the development and maintenance of the growth plate cartilage and deficiency of DDRGK1 recapitulate the clinical phenotype of short stature and joint abnormalities observed in patients with Shohat type SEMD (PMID:28263186; PMID:35377455).

This gene has been associated with relevant phenotype in OMIM (MIM #602557), but not in Gene2Phenotype.
Sources: Literature

Created: 24 Feb 2023, 7:22 p.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Spondyloepimetaphyseal dysplasia, Shohat type, OMIM:602557

Publications

• 28263186
• 35377455
• 35670300
• 36243336