Skeletal dysplasia

Gene: COG1

Green List (high evidence)

Dysostoses with predominant vertebral with and without costal involvement gp of SD. At least 3 cases reported - green; Review on behalf of Tracy Lester

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

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Congenital disorder of glycosylation, type IIg 611209

Publications

• 16537452
• 19008299

I don't know

Comment on list classification: 3 unrelated cases with plausible disease causing variants in the gene reported and a relevant phenotype.

Created: 20 Nov 2019, 11:10 p.m. | Last Modified: 20 Nov 2019, 11:10 p.m.

Panel Version: 1.221

Associated with Congenital disorder of glycosylation, type IIg #611209 (AR) in OMIM. Clinical features include short stature, several skeletal features such as scoliosis and vertebral abnormalities.

PMID: 16537452 - Foulquier et al 2006 - describe a patient with a mild form of congenital disorder of glycosylation type II with a homozygous insertion of a single nucleotide (2659-2660insC), which is predicted to lead to a premature translation stop and truncation of the C terminus of the Cog1 protein by 80 amino acids. Both parents were shown to be heterozygous for this mutation. Her skeletal features included small hands and feet, rhizomelic short stature.

PMID: 19008299 - Zeevaert et al 2009 - two patients (one with consanguineous Greek-Turkish parents, the other with unrelated Bulgarian parents) with a cerebrocostomandibular-like syndrome and an intronic mutation, c.1070+5G>A, that disrupts a splice donor site and leads to skipping of exon 6, a frameshift and a premature stopcodon in exon 7. Patient 1's characteristics included multiple congenital abnormalities including Pierre-Robin sequence (cleft palate, micrognathia and glossoptosis), costovertebral anomalies including osteopenia, ribfusions and posterior rib gaps, butterfly vertebrae, misalignment of the vertebrae and a clubfoot on the right. Patient 2 presented with rhizomelic shortening of upper limbs, ulnar deviation of fingers, thoracic scoliosis, hypospadias-I and left-side cryptorchidism among other features.

3 unrelated cases.

Created: 20 Nov 2019, 5:01 p.m. | Last Modified: 20 Nov 2019, 11:09 p.m.

Panel Version: 1.220

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: COG1; Initial rating suggestion: green

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

Comment when marking as ready: Associated with phenotype in OMIM and G2P. Only two variants reported

Created: 28 Jul 2016, 8:15 a.m.

Green List (high evidence)

Tier 2

Created: 17 Jun 2016, 8:02 a.m.

Mode of inheritance
Unknown

Phenotypes
Congenital disorder of glycosylation, type IIg 611209; Cerebro-costo-mandibular-like syndrome with vertebral defects

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