Arthrogryposis

Gene: CIAO1

I don't know

CIAO1 has been rated as amber on this panel (Arthrogryposis) as the contractures reported in PMID: 38950322 are limited to Achilles tendon. If further evidence is published, a green rating will be recommended for CIAO1 on this panel.

Created: 9 Sep 2024, 3:37 p.m. | Last Modified: 9 Sep 2024, 3:37 p.m.

Panel Version: 7.2

CIAO1 variants have not previously been associated with a phenotype (OMIM, Gen2Phen, Mondo or Orphanet). Maio et al (PMID: 38950322) report five biallelic CIAO1 variants in four unrelated individuals with a neuromuscular disorder with compromised nucleocytoplasmic Fe-S enzymes. The authors also report functional studies which reveal that the "CIAO1 variants failed to recruit Fe-S recipient proteins, resulting in compromised activities of DNA helicases, polymerases, and repair enzymes that rely on the CIA complex to acquire their Fe-S cofactors". In addition, they revealed that all patient-derived cellular abnormalities could be reversed using Lentivirus-mediated restoration of CIAO1 expression.

Created: 28 Aug 2024, 3:36 p.m. | Last Modified: 28 Aug 2024, 3:36 p.m.

Panel Version: 4.37

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Green List (high evidence)

Study reported at least 4 families with: "patients with biallelic loss of function in CIAO1 developed proximal and axial muscle weakness, fluctuating creatine kinase elevation, and respiratory insufficiency. In addition, they presented with CNS symptoms including learning difficulties and neurobehavioral comorbidities, along with iron deposition in deep brain nuclei, mild normocytic to macrocytic anemia, and gastrointestinal symptoms.".
Sources: Literature

Created: 24 Aug 2024, 1:12 p.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
myopathy

Publications

• 38950322