Arthrogryposis

Gene: COASY

Green List (high evidence)

The rating of this gene has been updated to green following NHS Genomic Medicine Service approval.

Created: 26 Sep 2024, 12:24 p.m. | Last Modified: 26 Sep 2024, 12:24 p.m.

Panel Version: 7.4

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Green List (high evidence)

Comment on list classification: There is sufficient evidence available for promoting this gene to green rating in the next GMS review.

Created: 25 Apr 2024, 9:51 a.m. | Last Modified: 25 Apr 2024, 9:51 a.m.

Panel Version: 5.31

PMID: 30089828 - Four individuals from two families were reported with biallelic COASY variants and with pontocerebellar hypoplasia (PCH), prenatal onset microcephaly, and arthrogryposis. Family 1 had compound heterozygous variants c.1549_1550delAG/ c.1486-3 C>G, whereas family 2 was homozygous for the c.1486-3 C>G variant.

PMID: 35499143 - Five more families reported with PCH and arthrogryposis and members from four of these families were homozygous for the same c.1486-3 C>G variant. All these reported families were from an endogamous community. But one family did not have the affected individuals sequenced, but they were presumed homozygous as parents are carriers. c.1486-3 C>G. The allele frequency of this variant is 0.62% in the available Asian Indian database.

PMID: 36495139 - Two siblings were identified with the homozygous c.1664G>A variant. However, they did not have either COASY-associated neurodegeneration or PCH. But, they presented with significant hypotonia and respiratory insufficiency at birth. They had bilateral finger contractures at birth/ initial examination.

Biallelic variants in COASY gene were associated with two different phenotypes in OMIM (MIMs #615643 & #618266), while with COASY-related neurodegeneration with brain accumulation phenotype in Gene2Phenotype database (with 'definitive' rating in the DD panel).

Created: 25 Apr 2024, 9:48 a.m. | Last Modified: 25 Apr 2024, 9:48 a.m.

Panel Version: 5.29

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Neurodegeneration with brain iron accumulation 6, OMIM:615643; Pontocerebellar hypoplasia, type 12, OMIM:618266; arthrogryposis, MONDO:0008779

Publications

• 30089828
• 35499143
• 36495139

I don't know

PMID: 35499143 reports five unrelated families affected with the disorder, with the previously reported COASY variant, c.1486-3C>G
Eight patients from four families were found to have arthrogryposis postnatally

Created: 17 Apr 2024, 2:30 p.m. | Last Modified: 17 Apr 2024, 2:30 p.m.

Panel Version: 5.22

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Pontocerebellar hypoplasia type 12

Publications

• PMID: 35499143

I don't know

Comment on list classification: New gene. Rated Amber until more cases on gene and disease association are reported.

Created: 3 Dec 2018, 11:17 a.m.

added watchlist tag

Created: 3 Dec 2018, 11:17 a.m.

From Dijk et al. (2018) PMID: 30089828 variants in the gene Coenzyme A (CoA) synthase (COASY) gene, an enzyme essential in CoA synthesis. A single variant was identified in 4 individuals in 2 unrelated families with PCH, prenatal onset microcephaly, and arthrogryposis. In both families, the variant c.[1549_1550delAG]; [1486-3 C>G] segregated wth the phenotype. No CoA synthase protein was detected in patient cells by immunoblot analysis and CoA synthase activity was virtually absent. Partial CoA synthase defects were previously described by Dusi et al. (2014) PMID: 24360804 as a cause of COASY Protein-Associated Neurodegeneration (CoPAN), a type of Neurodegeneration and Brain Iron Accumulation (MIM: 615643). Dijk et al. (2018) PMID: 30089828 demonstrate that near complete loss of function variants in COASY are associated with lethal PCH and arthrogryposis.
Sources: Literature

Created: 3 Dec 2018, 11:16 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Severe prenatal onset pontocerebellar hypoplasia, microcephaly, arthrogryposis

Publications

• 30089828
• 24360804