OBJECTIVE: To characterise the phenotype of a family with paroxysmal exercise induced dystonia (PED) and migraine and establish whether it is linked to the paroxysmal non-kinesigenic dyskinesia (PNKD) locus on chromosome 2q33-35, the familial hemiplegic migraine (FHM) locus on chromosome 19p, or the familial infantile convulsions and paroxysmal choreoathetosis (ICCA syndrome) locus on chromosome 16. METHODS: A family, comprising 30 members, was investigated. Fourteen family members in two generations including three spouses were examined. Haplotypes were reconstructed for all the available family members by typing several microsatellite markers spanning the PNKD, FHM, and ICCA loci. Additionally, the four exons containing the known FHM mutations were sequenced. RESULTS: Of 14 members examined four were definitely affected and one member was affected by history. The transmission pattern in this family was autosomal dominant with reduced penetrance. Mean age of onset in affected members was 12 (range 9-15 years). Male to female ratio was 3:1. Attacks of PED in affected members were predominantly dystonic and lasted between 15 and 30 minutes. They were consistently precipitated by walking but could also occur after other exercise. Generalisation did not occur. Three of the affected members in the family also had migraine without aura. Linkage of the disease to the PNKD, FHM, or ICCA loci was excluded as no common haplotype was shared by all the affected members for each locus. In addition, direct DNA sequential analysis of the FHM gene (CACNL1A4) ruled out all known FHM point mutations. CONCLUSIONS: This family presented with the classic phenotype of PED and is not linked to the PNKD, FHM, or ICCA loci. A new gene, possibly coding for an ion channel, is likely to be the underlying cause of the disease.
OBJECTIVE: To characterise the phenotype of a family with paroxysmal exercise induced dystonia (PED) and migraine and establish whether it is linked to the paroxysmal non-kinesigenic dyskinesia (PNKD) locus on chromosome 2q33-35, the familial hemiplegic migraine (FHM) locus on chromosome 19p, or the familial infantile convulsions and paroxysmal choreoathetosis (ICCA syndrome) locus on chromosome 16. METHODS: A family, comprising 30 members, was investigated. Fourteen family members in two generations including three spouses were examined. Haplotypes were reconstructed for all the available family members by typing several microsatellite markers spanning the PNKD, FHM, and ICCA loci. Additionally, the four exons containing the known FHM mutations were sequenced. RESULTS: Of 14 members examined four were definitely affected and one member was affected by history. The transmission pattern in this family was autosomal dominant with reduced penetrance. Mean age of onset in affected members was 12 (range 9-15 years). Male to female ratio was 3:1. Attacks of PED in affected members were predominantly dystonic and lasted between 15 and 30 minutes. They were consistently precipitated by walking but could also occur after other exercise. Generalisation did not occur. Three of the affected members in the family also had migraine without aura. Linkage of the disease to the PNKD, FHM, or ICCA loci was excluded as no common haplotype was shared by all the affected members for each locus. In addition, direct DNA sequential analysis of the FHM gene (CACNL1A4) ruled out all known FHM point mutations. CONCLUSIONS: This family presented with the classic phenotype of PED and is not linked to the PNKD, FHM, or ICCA loci. A new gene, possibly coding for an ion channel, is likely to be the underlying cause of the disease.
Authors: P W Reed; J L Davies; J B Copeman; S T Bennett; S M Palmer; L E Pritchard; S C Gough; Y Kawaguchi; H J Cordell; K M Balfour Journal: Nat Genet Date: 1994-07 Impact factor: 38.330
Authors: Yvonne G Weber; Alexander Storch; Thomas V Wuttke; Knut Brockmann; Judith Kempfle; Snezana Maljevic; Lucia Margari; Christoph Kamm; Susanne A Schneider; Stephan M Huber; Arnulf Pekrun; Robert Roebling; Guiscard Seebohm; Saisudha Koka; Camelia Lang; Eduard Kraft; Dragica Blazevic; Alberto Salvo-Vargas; Michael Fauler; Felix M Mottaghy; Alexander Münchau; Mark J Edwards; Anna Presicci; Francesco Margari; Thomas Gasser; Florian Lang; Kailash P Bhatia; Frank Lehmann-Horn; Holger Lerche Journal: J Clin Invest Date: 2008-06 Impact factor: 14.808
Authors: Alexander J A Groffen; Thom Klapwijk; Anne-Fleur van Rootselaar; Justus L Groen; Marina A J Tijssen Journal: J Neurol Date: 2012-06-30 Impact factor: 4.849
Authors: Arvid Suls; Peter Dedeken; Karolien Goffin; Hilde Van Esch; Patrick Dupont; David Cassiman; Judith Kempfle; Thomas V Wuttke; Yvonne Weber; Holger Lerche; Zaid Afawi; Wim Vandenberghe; Amos D Korczyn; Samuel F Berkovic; Dana Ekstein; Sara Kivity; Philippe Ryvlin; Lieve R F Claes; Liesbet Deprez; Snezana Maljevic; Alberto Vargas; Tine Van Dyck; Dirk Goossens; Jurgen Del-Favero; Koen Van Laere; Peter De Jonghe; Wim Van Paesschen Journal: Brain Date: 2008-06-24 Impact factor: 13.501