The Phenotype of the X-Linked Dystonia-Parkinsonism Syndrome An Assessment of 42 Cases in the Philippines

Lee, Lillian V.; Kupke, Kenneth G.; Caballar-gonzaga, Flor; Hebron-ortiz, Marilyn; Müller, Ulrich

doi:10.1097/00005792-199105000-00002

Cited by 91 publications

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“…XDP patients were the same as those investigated before (1,11). Controls included the 105 Filipino males studied before (1,11) and an additional 73 male and female adult Filipinos (comprising 103 X chromosomes) with a negative family history of XDP. Blood was drawn after informed consent.…”

Section: Methodsmentioning

confidence: 99%

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Specific sequence changes in multiple transcript system DYT3 are associated with X-linked dystonia parkinsonism

Nolte

Niemann

Müller

2003

Proc. Natl. Acad. Sci. U.S.A.

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125

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X-linked dystonia parkinsonism (XDP) is an X-linked recessive adult onset movement disorder characterized by both dystonia and parkinsonism. We report delineation of the disease gene within a 300-kb interval of Xq13.1 by allelic association. Sequencing of this region in a patient revealed five disease-specific single-nucleotide changes (here referred to as DSC) and a 48-bp deletion unique to XDP. One of the DSCs is located within an exon of a not previously described multiple transcript system that is composed of at least 16 exons. There is a minimum of three different transcription start sites that encode four different transcripts. Two of these transcripts include distal portions of the TAF1 gene (TATA-box binding protein-associated factor 1) and are alternatively spliced. Three exons overlap with ING2 (a putative tumor suppressor) and with a homologue of CIS4 (cytokine-inducible SH2 protein 4), both of which are encoded by the opposite strand. Although all DSCs are located within this multiple transcript system, only DSC3 lies within an exon. This exon is used by all alternative transcripts making a pathogenic role of DSC3 in XDP likely. The multiple transcript system is therefore referred to as DYT3 (disease locus in XDP).X chromosome ͉ positional cloning ͉ single-nucleotide polymorphism ͉ alternative splicing ͉ transcription factor

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Section: Methodsmentioning

confidence: 99%

“…314215) is an X-linked recessive adult onset movement disorder characterized by generalized dystonia and parkinsonism in Ϸ50% of cases (1,2). The disease is invariably fatal, and death occurs after a duration of up to 40 years by starvation (due to oropharyngeal dystonia) or secondary infections (mainly aspiration pneumonia).…”

mentioning

confidence: 99%

Specific sequence changes in multiple transcript system DYT3 are associated with X-linked dystonia parkinsonism

Nolte

Niemann

Müller

2003

Proc. Natl. Acad. Sci. U.S.A.

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125

122

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“…In many reported cases, it is often medication resistant or minimally responsive to pharmacologic treatment [2] . The disabling symptoms have also been surgically refractory in the limited available reports in the literature where thalamotomy was employed [3,4] .…”

Section: Introductionmentioning

confidence: 99%

Differential Response of Dystonia and Parkinsonism following Globus Pallidus Internus Deep Brain Stimulation in X-Linked Dystonia-Parkinsonism (Lubag)

Oyama¹,

Fernández²,

Foote³

et al. 2010

Stereotact Funct Neurosurg

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Background: X-linked dystonia-parkinsonism (XDP; DYT3; Lubag) is an adult-onset hereditary progressive dystonia/parkinsonism which is typically minimally responsive to pharmacological treatment. Case Report: We report a 63- year-old man with a diagnosis of XDP who underwent bilateral globus pallidus internus deep brain stimulator (GPi-DBS) placement. His course initially began with right hand tremor and dystonia at age 57 and progressed to also include bradykinesia and rigidity. The patient tolerated the procedure without significant complications. GPi-DBS improved his right hand dystonia, but did not significantly improve his parkinsonism. Conclusion: DBS may be a therapeutic option for select cases of XDP, but its specificindications must be carefully discussed, as the available cases have had mixed responses. Whether other targets may be more effective is not known.

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“…The X chromosome-linked dystonia-parkinsonism syndrome (XDP) is a severe movement disorder most likely caused by a malfunction of the basal ganglia (1)(2)(3). XDP is characterized by dystonia-i.e., "involuntary, sustained muscle contractions resulting in twisting and repetitive movements, or abnormal postures" (4), and concurrent parkinsonian symptoms in a significant percentage of patients (2,5).…”

mentioning

confidence: 99%

“…XDP is characterized by dystonia-i.e., "involuntary, sustained muscle contractions resulting in twisting and repetitive movements, or abnormal postures" (4), and concurrent parkinsonian symptoms in a significant percentage of patients (2,5). The mean age of onset of XDP is 35 ± 8 years (range, 12-50 years) with an age-dependent penetrance apparently complete by the end of the 5th decade (2). The prevalence of XDP is highest in the Philippine island of Panay, where it probably originated from a single mutation (founder effect).…”

mentioning

confidence: 99%

Delineation of the dystonia-parkinsonism syndrome locus in Xq13.

Graeber

Kupke

Müller

1992

Proc. Natl. Acad. Sci. U.S.A.

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The X chromosome-linked dystonia-parkinsonism syndrome (XDP) is a severe movement disorder, characterized by both dystonia and parkinsonism. XDP is a genetically homogeneous disorder. Known ancestry of all patients has been traced back to Panay, Philippines, where the disease probably originated from a single mutation (founder effect). The gene locus, DYT3, has been previously assigned to the proximal long arm of the X chromosome (Xql2-q21.1). Using four dinucleotide tandem repeat (DNTR) sequences from Xql3-derived yeast artificial chromosomes (YACs), we further delineate DYT3 within Xql3. Observation of a recombination event between DYT3 and DNTR locus 4548-7, derived from a YAC encompassing locus DXS56, establishes 4548-7 as a distal flanking marker. Assignment of DYT3 to a region in Xql3, flanked by loci 4548-7 and DXS159, is further supported by highly significant allelic association between DYT3 and a total of four DNTR loci-PY2-31, PY5-10, 4548-1, and 4548-7-located in a region defied by PGKI and DXS56. 1k1 and JAl values were 0.82/0.35, 0.78/0.42, 0.65/0.34, and 0.88/0.58 for PY2-31 , PY5-10, 4548-1, and 4548-7 atP < 10-2, P < 10-4, P < 10-3, and P < 10-6.The X chromosome-linked dystonia-parkinsonism syndrome (XDP) is a severe movement disorder most likely caused by a malfunction of the basal ganglia (1-3). XDP is characterized by dystonia-i.e., "involuntary, sustained muscle contractions resulting in twisting and repetitive movements, or abnormal postures" (4), and concurrent parkinsonian symptoms in a significant percentage of patients (2, 5). The mean age of onset of XDP is 35 ± 8 years (range, 12-50 years) with an age-dependent penetrance apparently complete by the end of the 5th decade (2). The prevalence of XDP is highest in the Philippine island of Panay, where it probably originated from a single mutation (founder effect). Known ancestry of patients, including those diagnosed in North America, has been traced back to Panay, Philippines. XDP thus appears to be a genetically homogeneous disorder.Idiopathic parkinsonism, clinically characterized by a combination of the symptoms bradykinesia, rigidity, tremor, and loss of postural reflexes, affects ==1% of all Americans older than 50 years (6). The major neuropathologic findings are loss of dopaminergic neurons, notably in the substantia nigra and related nuclei (7). The cause of this degeneration is unclear. Unlike XDP, idiopathic parkinsonism is usually not inherited as a Mendelian trait, and both environmental and genetic factors are implicated in its etiology. The genetic component of the disorder is presently not amenable to analysis.Knowledge of genes involved in pathogenesis of basal ganglia dysfunction may greatly contribute to a better understanding ofboth dystonia and parkinsonism. One approach to identify such genes is the investigation of rare genetic disorders, which are inherited as Mendelian traits. Due to its genetic homogeneity and X chromosome-linked recessive mode of inheritance, XDP is well suited for such analysis.In an ef...

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The Phenotype of the X-Linked Dystonia-Parkinsonism Syndrome An Assessment of 42 Cases in the Philippines

Cited by 91 publications

References 0 publications

Specific sequence changes in multiple transcript system DYT3 are associated with X-linked dystonia parkinsonism

Specific sequence changes in multiple transcript system DYT3 are associated with X-linked dystonia parkinsonism

Differential Response of Dystonia and Parkinsonism following Globus Pallidus Internus Deep Brain Stimulation in X-Linked Dystonia-Parkinsonism (Lubag)

Delineation of the dystonia-parkinsonism syndrome locus in Xq13.

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