A family with spinocerebellar ataxia type 8 expansion and vitamin E deficiency ataxia.
BACKGROUND
Ataxia with vitamin E deficiency is a recessive autosomal neurodegenerative disorder resembling the Friedreich ataxia phenotype but is due to mutations in the alpha-tocopherol transfer protein (TTPA) gene. In a recent article, we described a patient with ataxia carrying reduced serum vitamin E levels and showing CTA/CTG expansions of 320 triplet repeats in the SCA8 gene.


OBJECTIVE
To perform a screening of the TTPA gene in the patient and to evaluate the effects of treatment with vitamin E on the patient's neurologic disturbances.


METHODS
We performed a single-strand conformation polymorphism and nucleotide sequence analysis of the 5 exons of the TTPA gene in the patient's family members.


RESULTS
The results indicated the patient to be a compound heterozygote for 2 mutations (in exon 3), each transmitted by one of the 2 parents, yielding a nonfunctional protein.


CONCLUSIONS
We describe for the first time, to our knowledge, a mutated form of the TTPA gene in a patient also carrying an expansion in the SCA8 gene. The lack of improvement in the patient's symptoms on supplementation with alpha-tocopherol suggests that the SCA8 mutations may act in the neurodegeneration process, worsening the neurologic signs caused by the vitamin E deficit, and it could be speculated that the co-occurrence of mutant alleles for 2 distinct loci may influence the clinical course of the disease.
Cellini
Elena
E
Department of Neurological and Psychiatric Sciences, University of Florence, Italy.
Piacentini
Silvia
S
Nacmias
Benedetta
B
Forleo
Paolo
P
Tedde
Andrea
A
Bagnoli
Silvia
S
Ciantelli
Monica
M
Sorbi
Sandro
S
D000328:Adult; D002352:Carrier Proteins / Q000235:genetics*; D005260:Female; D006801:Humans; D008297:Male; D009419:Nerve Tissue Proteins / Q000235:genetics*; D010375:Pedigree; D062085:RNA, Long Noncoding; D022661:RNA, Untranslated; D020754:Spinocerebellar Ataxias / Q000235:genetics*; D019680:Trinucleotide Repeat Expansion / Q000235:genetics*; D014811:Vitamin E Deficiency / Q000235:genetics*
C415906:ATXN8OS gene product, human; D002352:Carrier Proteins; D009419:Nerve Tissue Proteins; D062085:RNA, Long Noncoding; D022661:RNA, Untranslated; C017763:alpha-tocopherol transfer protein