A novel c.5308_5311delGAGA mutation in Senataxin in a Cypriot family with an autosomal recessive cerebellar ataxia.
BACKGROUND
Senataxin (chromosome 9q34) was recently identified as the causative gene for an autosomal recessive form of Ataxia (ARCA), termed as Ataxia with Oculomotor Apraxia, type 2 (AOA2) and characterized by generalized incoordination, cerebellar atrophy, peripheral neuropathy, "oculomotor apraxia" and increased alpha-fetoprotein (AFP). Here, we report a novel Senataxin mutation in a Cypriot ARCA family.


METHODS
We studied several Cypriot autosomal recessive cerebellar ataxia (ARCA) families for linkage to known ARCA gene loci. We linked one family (909) to the SETX locus on chromosome 9q34 and screened the proband for mutations by direct sequencing.


RESULTS
Sequence analysis revealed a novel c.5308_5311delGAGA mutation in exon 11 of the SETX gene. The mutation has not been detected in 204 control chromosomes from the Cypriot population, the remaining Cypriot ARCA families and 37 Cypriot sporadic cerebellar ataxia patients.


CONCLUSIONS
We identified a novel SETX homozygous c.5308_5311delGAGA mutation that co-segregates with ARCA with cerebellar atrophy and raised AFP.
Nicolaou
Paschalis
P
The Cyprus Institute of Neurology and Genetics, 6 International Airport Avenue, Nicosia, Cyprus. paschali@cing.ac.cy
Georghiou
Anthi
A
Votsi
Christina
C
Middleton
Lefkos T
LT
Zamba-Papanicolaou
Eleni
E
Christodoulou
Kyproula
K
D000293:Adolescent; D000595:Amino Acid Sequence; D001921:Brain / Q000473:pathology; D002524:Cerebellar Ataxia / Q000235:genetics* / Q000473:pathology; D002648:Child; D002899:Chromosomes, Human, Pair 9; D003535:Cyprus; D004265:DNA Helicases; D005260:Female; D005808:Genes, Recessive; D006801:Humans; D008126:Lod Score; D008279:Magnetic Resonance Imaging; D008297:Male; D064251:Multifunctional Enzymes; D010375:Pedigree; D020365:RNA Helicases / Q000235:genetics*; D017384:Sequence Deletion
D064251:Multifunctional Enzymes; C484368:SETX protein, human; D004265:DNA Helicases; D020365:RNA Helicases