CAMOS, a nonprogressive, autosomal recessive, congenital cerebellar ataxia, is caused by a mutant zinc-finger protein, ZNF592.

Abstract

CAMOS (Cerebellar Ataxia with Mental retardation, Optic atrophy and Skin abnormalities) is a rare autosomal recessive syndrome characterized by a nonprogressive 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 3.6-cM 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-amino-acid zinc-finger (ZnF) protein, and the mutation, located within the eleventh ZnF, is predicted to affect the DNA-binding properties of ZNF592. 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.

• Authors: Elsa Nicolas, Yannick Poitelon, Eliane Chouery, Nabiha Salem, Nicolas Levy, André Mégarbané, Valérie Delague
• Journal: European journal of human genetics : EJHG (Eur J Hum Genet) Vol. 18 Issue 10 Pg. 1107-13 (Oct 2010) ISSN: 1476-5438 [Electronic] England
• PMID: 20531441 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• DNA-Binding Proteins
• Genetic Markers
• Mutant Proteins
• ZNF592 protein, human

Topics

• Amino Acid Sequence
• Chromosome Mapping
• Chromosomes, Human, Pair 15
• DNA-Binding Proteins (chemistry, genetics, metabolism)
• Disease Progression
• Family Health
• Gene Expression Regulation
• Genes, Recessive
• Genetic Linkage
• Genetic Markers
• Humans
• Intellectual Disability (genetics)
• Lebanon
• Molecular Sequence Data
• Mutant Proteins (chemistry, genetics, metabolism)
• Mutation, Missense
• Spinocerebellar Degenerations (genetics)
• Zinc Fingers