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

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.

• Authors: Aloysius Domingo, Lillian V Lee, Norbert Brüggemann, Karen Freimann, Frank J Kaiser, Roland D G Jamora, Raymond L Rosales, Christine Klein, Ana Westenberger
• Journal: JAMA neurology (JAMA Neurol) Vol. 71 Issue 9 Pg. 1177-80 (Sep 2014) ISSN: 2168-6157 [Electronic] United States
• PMID: 25004170 (Publication Type: Case Reports, Journal Article, Research Support, Non-U.S. Gov't)

Topics

• Aged
• Dystonic Disorders (genetics, pathology, physiopathology)
• Female
• Genetic Diseases, X-Linked (genetics, pathology, physiopathology)
• Genetic Testing
• Humans
• Philippines
• Sex Factors
• X Chromosome Inactivation (genetics)