CAMOS, a nonprogressive, autosomal recessive, congenital cerebellar ataxia, is caused by a mutant zinc-finger protein, ZNF592.
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.
Nicolas
Elsa
E
Faculté de Médecine de la Timone, INSERM UMR_S 910, Génétique Médicale et Génomique Fonctionnelle, Université de la Méditerranée, Marseille, France.
Poitelon
Yannick
Y
Chouery
Eliane
E
Salem
Nabiha
N
Levy
Nicolas
N
Mégarbané
André
A
Delague
Valérie
V
D000595:Amino Acid Sequence; D002874:Chromosome Mapping; D002884:Chromosomes, Human, Pair 15; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D018450:Disease Progression; D005192:Family Health; D005786:Gene Expression Regulation; D005808:Genes, Recessive; D008040:Genetic Linkage; D005819:Genetic Markers; D006801:Humans; D008607:Intellectual Disability / Q000235:genetics; D007861:Lebanon; D008969:Molecular Sequence Data; D050505:Mutant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D020125:Mutation, Missense; D013132:Spinocerebellar Degenerations / Q000235:genetics; D016335:Zinc Fingers
D004268:DNA-Binding Proteins; D005819:Genetic Markers; D050505:Mutant Proteins; C555602:ZNF592 protein, human