title: Woman with x-linked recessive dystonia-parkinsonism: clue to the epidemiology of parkinsonism in Filipino women?
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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
  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.affiliation: 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.
authors.forename: Aloysius
authors.initials: A
authors.lastname: Domingo
authors.affiliation: XDP Study Group, Philippine Children's Medical Center, Quezon City, Philippines.
authors.forename: Lillian V
authors.initials: LV
authors.lastname: Lee
authors.affiliation: Institute of Neurogenetics, University of Lübeck, Lübeck, Germany.
authors.forename: Norbert
authors.initials: N
authors.lastname: Brüggemann
authors.affiliation: Institute of Neurogenetics, University of Lübeck, Lübeck, Germany.
authors.forename: Karen
authors.initials: K
authors.lastname: Freimann
authors.affiliation: Institute of Human Genetics, University of Lübeck, Lübeck, Germany.
authors.forename: Frank J
authors.initials: FJ
authors.lastname: Kaiser
authors.affiliation: XDP Study Group, Philippine Children's Medical Center, Quezon City, Philippines5Department of Neurosciences, University of the Philippines, Manila-Philippine General Hospital, Manila.
authors.forename: Roland D G
authors.initials: RD
authors.lastname: Jamora
authors.affiliation: XDP Study Group, Philippine Children's Medical Center, Quezon City, Philippines6Faculty of Neurology and Psychiatry, University of Santo Tomas Hospital, Manila, Philippines.
authors.forename: Raymond L
authors.initials: RL
authors.lastname: Rosales
authors.affiliation: Institute of Neurogenetics, University of Lübeck, Lübeck, Germany.
authors.forename: Christine
authors.initials: C
authors.lastname: Klein
authors.affiliation: Institute of Neurogenetics, University of Lübeck, Lübeck, Germany.
authors.forename: Ana
authors.initials: A
authors.lastname: Westenberger
mesh_terms: D000368:Aged; D020821:Dystonic Disorders / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D005260:Female; D040181:Genetic Diseases, X-Linked / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D005820:Genetic Testing; D006801:Humans; D010679:Philippines; D012737:Sex Factors; D049951:X Chromosome Inactivation / Q000235:genetics