Effects of a polymorphism in the GFAP promoter on the age of onset and ambulatory disability in late-onset Alexander disease.

[alexander disease]

Alexander disease (AxD ) is a rare neurodegenerative disorder . Most patients with AxD have a de novo dominant missense mutation in the glial fibrillary acidic protein (GFAP ) gene . Patients with late-onset AxD exhibit a more variable onset and severity than patients with early -onset AxD , suggesting the existence of factors that modify the clinical phenotype of late-onset AxD . A -250 -bp C /A single -nucleotide polymorphism (SNP ) of the GFAP promoter (rs 2070935 ) in the activator protein-1 binding site is a candidate factor for modification of the clinical phenotype . We analyzed the SNP in 10 patients with late-onset AxD and evaluated the effects of the SNP on the clinical course of late-onset AxD . Three of four cases with the C /C genotype lost the ability to walk in their 30 s or 40 s , whereas all six cases with the other genotypes retained the ability to walk throughout their 30 s . The age of onset in patients with the C /C genotype was significantly earlier than in patients with the other genotypes (P <0 .05 ). A more severe phenotype was observed in the patient in whom the C allele of rs 2070935 was in cis with the GFAP mutation compared with the patient in whom the C allele of rs 2070935 was in trans with the GFAP mutation . Our investigation revealed the possibility that the C /C genotype at rs 2070935 of the GFAP promoter in late-onset AxD was associated with an earlier onset and a more rapid progression of ambulatory disability compared with the other genotypes .

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Diseases presenting "an earlier onset" symptom

alexander disease

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