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Title: Paroxysmal dystonic choreoathetosis: Tight linkage to chromosome 2q

Abstract

Paroxysmal dystonic choreoathetosis (PDC) is characterized by attacks of involuntary movements that last up to several hours and occur at rest both spontaneously and following caffeine or alcohol consumption. We analyzed a Polish-American kindred with autosomal dominant PDC and identified tight linkage between the disorder and microsatellite markers on chromosome 2q (maximum two-point LOD score 4.77; recombination fraction 0). Our results clearly establish the existence of a locus for autosomal dominant PDC on distal chromosome 2q. The fact that three other paroxysmal neurological disorders (periodic ataxia with myokymia and hypo- and hyperkalemic periodic paralysis) are due to mutation in ion-channel genes raises the possibility that PDC is also due to an ion-channel gene mutation. It is noteworthy that a cluster of sodium-channel genes is located on distal chromosome 2q, near the PDC locus. Identifying the PDC locus on chromosome 2q will facilitate discovery whether PDC is genetically homogeneous and whether other paroxysmal movement disorders are also genetically linked to the PDC locus. 28 refs., 2 figs., 1 tab.

Authors:
; ; ;  [1]
  1. Univ. of Michigan, Ann Arbor, MI (United States) [and others
Publication Date:
OSTI Identifier:
443745
Resource Type:
Journal Article
Resource Relation:
Journal Name: American Journal of Human Genetics; Journal Volume: 59; Journal Issue: 1; Other Information: PBD: Jul 1996
Country of Publication:
United States
Language:
English
Subject:
55 BIOLOGY AND MEDICINE, BASIC STUDIES; PATIENTS; HEREDITARY DISEASES; PHENOTYPE; NERVOUS SYSTEM DISEASES; GENOTYPE; GENES; GENE MUTATIONS; GENETIC MAPPING; HUMAN CHROMOSOME 2; C CODES; DOMINANT MUTATIONS; STATISTICS; GENETICS; BIOLOGICAL MARKERS; PORINS

Citation Formats

Fink, J.K., Rainier, S., Wilkowski, J., and Jones, S.M. Paroxysmal dystonic choreoathetosis: Tight linkage to chromosome 2q. United States: N. p., 1996. Web.
Fink, J.K., Rainier, S., Wilkowski, J., & Jones, S.M. Paroxysmal dystonic choreoathetosis: Tight linkage to chromosome 2q. United States.
Fink, J.K., Rainier, S., Wilkowski, J., and Jones, S.M. 1996. "Paroxysmal dystonic choreoathetosis: Tight linkage to chromosome 2q". United States. doi:.
@article{osti_443745,
title = {Paroxysmal dystonic choreoathetosis: Tight linkage to chromosome 2q},
author = {Fink, J.K. and Rainier, S. and Wilkowski, J. and Jones, S.M.},
abstractNote = {Paroxysmal dystonic choreoathetosis (PDC) is characterized by attacks of involuntary movements that last up to several hours and occur at rest both spontaneously and following caffeine or alcohol consumption. We analyzed a Polish-American kindred with autosomal dominant PDC and identified tight linkage between the disorder and microsatellite markers on chromosome 2q (maximum two-point LOD score 4.77; recombination fraction 0). Our results clearly establish the existence of a locus for autosomal dominant PDC on distal chromosome 2q. The fact that three other paroxysmal neurological disorders (periodic ataxia with myokymia and hypo- and hyperkalemic periodic paralysis) are due to mutation in ion-channel genes raises the possibility that PDC is also due to an ion-channel gene mutation. It is noteworthy that a cluster of sodium-channel genes is located on distal chromosome 2q, near the PDC locus. Identifying the PDC locus on chromosome 2q will facilitate discovery whether PDC is genetically homogeneous and whether other paroxysmal movement disorders are also genetically linked to the PDC locus. 28 refs., 2 figs., 1 tab.},
doi = {},
journal = {American Journal of Human Genetics},
number = 1,
volume = 59,
place = {United States},
year = 1996,
month = 7
}
  • Autosomal dominant, uncomplicated familial spastic paraplegia (FSP) is a genetically heterogeneous disorder characterized by insidiously progressive lower-extremity spasticity. Recently, a locus on chromosome 14q was shown to be tightly linked with the disorder in one of three families. We performed linkage analysis in a kindred with autosomal dominant uncomplicated FSP. After excluding the chromosome 14q locus, we observed tight linkage of the disorder to a group of markers on chromosome 15q (maximum two-point lod score 9.70; {theta} = .05). Our results clearly establish the existence of a locus for autosomal dominant FSP in the centromeric region of chromosome 15q. Comparingmore » clinical and genetic features in FSP families linked to chromosome 14q with those linked to chromosome 15q may provide insight into the pathophysiology of this disorder. 34 refs., 1 fig., 1 tab.« less
  • Familial spastic paraplegia (FSP) (MIM No.18260) constitutes a clinically and genetically diverse group of disorders that share the primary feature of progressive, severe, lower extremity spasticity. FSP is classified according to the mode of inheritance and whether progressive spasticity occurs in isolation ({open_quotes}uncomplicated FSP{close_quotes}) or with other neurologic abnormalities ({open_quotes}complicated FSP{close_quotes}), including optic neuropathy, retinopathy, extrapyramidal disturbance, dementia, ataxia, ichthyosis, mental retardation, or deafness. Recently, autosomal dominant, uncomplicated FSP was shown to be genetically heterogeneous and tightly linked to a group of microsatellite markers on chromosome 14q in one large kindred. We examined 126 members of a non-consanguineous North Americanmore » kindred of Irish descent. FSP was diagnosed in 31 living subjects who developed insidiously progressive gait disturbance between ages 12 and 35 years. Using genetic linkage analysis to microsatellite DNA polymorphisms, we showed that the FSP locus on chromosome 14q was exluded from linkage with the disorder in our family. Subsequently, we searched for genetic linkage between the disorder and microsatellite DNA polymorphisms spanning approximately 50% of the genome. We observed significantly positive, two-point maximum lod scores (Z) for markers on chromosome 15q: D15S128 (Z=9.70, {theta}=0.05), D15S165 (Z=3.30, {theta}=0.10), and UT511 (Z=3.86, {theta}=0.10). Our data clearly establishes that one locus for autosomal dominant, uncomplicated FSP is mapped to the pericentric region of chromosome 15q. Identifying genes responsible for chromosome 15q-linked and chromosome 14q-linked FSP will greatly advance our understanding of this condition and hopefully other inherited and degenerative brain and spinal cord disorders that are also characterized by axonal degeneration.« less
  • ADP/ATP translocase genes play a key role in the energy metabolism of the eukaryotic cell, catalyzing the exchange of ATP and ADP across the mitochondrial membrane. They are members of a gene family composed of three highly conserved human genes and at least nine pseudogenes. All share significant sequence similarity, suggesting their evolutionary origin from a common ancestral gene. ANT1 has been linked to markers on chromosome 7p, ANT3 maps to the pseudoautosomal region (PAR) on the short arm of the X chromosome, 1.3 Mb from the telomere, proximal to the pseudoautosomal genes CSF2RA and 113RA, and ANT2 has beenmore » previously assigned to the long arm of the X chromosome Xq. In this study, we used somatic cell hybrids containing different portions of the human X chromosome to confirm the localization of ANT2 to the long arm of the X chromosome and to assign it regionally to Xq24-q27. 13 refs., 1 fig.« less
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