CAMOS, a non-progressive, autosomal recessive, congenital cerebellar ataxia, is caused by a mutant Zinc-Finger protein, ZNF592.

Valérie Delague (1) , Elsa Nicolas (1) , Yannick Poitelon (1) , Eliane Chouery (1) , Nabiha Salem (1) , Nicolas Lévy (1) , André Mégarbané (1)

1 GMGF - Génétique Médicale et Génomique Fonctionnelle

CAMOS (Cerebellar Ataxia with Mental retardation, Optic atrophy and Skin abnormalities) is a rare autosomal recessive syndrome characterized by a non-progressive congenital Cerebellar ataxia associated with Mental retardation, Optic atrophy and Skin abnormalities. Using homozygosity mapping in a large inbred Lebanese Druze family, we previously reported the mapping of the disease gene at chromosome 15q24-q26 to a 3.6cM interval between markers D15S206 and D15S199. Screening of candidate genes lying in this region led to the identification of a homozygous p.Gly1046Arg missense mutation in ZNF592, in all five affected individuals of the family. ZNF592 encodes a 1267-aa zinc finger protein, and the mutation, located within the eleventh zinc finger, is predicted to affect ZNF592 's DNA binding properties. Although the precise role of ZNF592 remains to be determined, our results suggest that ZNF592 is implicated in a complex developmental pathway, and that the mutation is likely to disturb the highly orchestrated regulation of genes during cerebellar development, by either disrupting interactions with target DNA or with a partner protein.

Mots clés: CAMOS; cerebellar ataxia; ZNF592

Valérie Delague, Elsa Nicolas, Yannick Poitelon, Eliane Chouery, Nabiha Salem, et al.. CAMOS, a non-progressive, autosomal recessive, congenital cerebellar ataxia, is caused by a mutant Zinc-Finger protein, ZNF592.. European Journal of Human Genetics, 2010, ⟨10.1038/ejhg.2010.82⟩. ⟨hal-00544823⟩