Journal
JAMA NEUROLOGY
Volume 71, Issue 9, Pages 1177-1180Publisher
AMER MEDICAL ASSOC
DOI: 10.1001/jamaneurol.2014.56
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Funding
- Parkinson Foundation
- German Academic Exchange Service (DAAD)
- German Research Foundation (DFG) [LO 1555/3-2]
- Herman and Lilly Schilling Foundation
- Bachmann-Strauss Dystonia
- Dystonia Medical Research Foundation
- Fritz Thyssen Foundation
- University of Lubeck, Germany
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IMPORTANCE Despite recessive inheritance, X-linked dystonia-parkinsonism (Lubag disease) has also been described in women presenting with a late-onset isolated parkinsonian syndrome. Interestingly, unlike in other populations, there is a slight female predominance in the prevalence of parkinsonism in the Philippines. OBSERVATIONS In a Filipino woman with suspected Parkinson disease, we confirmed the presence of all changes specific for X-linked dystonia-parkinsonism in genomic DNA. Subsequently, we analyzed complementary DNA and evaluated the methylation status of the androgen receptor gene. Owing to extremely skewed (98%:2%) X-chromosome inactivation, the patient expressed almost solely the mutated allele in a disease-specific change, rendering her molecularly comparable with a hemizygously affected man. CONCLUSIONS AND RELEVANCE Skewed X-chromosome inactivation is the likely cause of parkinsonism in this heterozygous mutation carrier. Because women carriers of the genetic changes specific for X-linked dystonia-parkinsonism are common in the Philippines, the epigenetic factor of nonrandom X-chromosome inactivation may contribute to the skewing of the sex prevalence of parkinsonism toward women in this country, warranting further investigation.
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