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JAMA Neurol. 2014 Sep;71(9):1177-80. doi: 10.1001/jamaneurol.2014.56.

Woman with x-linked recessive dystonia-parkinsonism: clue to the epidemiology of parkinsonism in Filipino women?

Author information

1
Institute of Neurogenetics, University of Lübeck, Lübeck, Germany2XDP Study Group, Philippine Children's Medical Center, Quezon City, Philippines3Graduate School for Computing in Medicine and Life Sciences, University of Lübeck, Lübeck, Germany.
2
XDP Study Group, Philippine Children's Medical Center, Quezon City, Philippines.
3
Institute of Neurogenetics, University of Lübeck, Lübeck, Germany.
4
Institute of Human Genetics, University of Lübeck, Lübeck, Germany.
5
XDP Study Group, Philippine Children's Medical Center, Quezon City, Philippines5Department of Neurosciences, University of the Philippines, Manila-Philippine General Hospital, Manila.
6
XDP Study Group, Philippine Children's Medical Center, Quezon City, Philippines6Faculty of Neurology and Psychiatry, University of Santo Tomas Hospital, Manila, Philippines.

Abstract

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.

PMID:
25004170
DOI:
10.1001/jamaneurol.2014.56
[Indexed for MEDLINE]

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