The Experts below are selected from a list of 573 Experts worldwide ranked by ideXlab platform
John G Nutt - One of the best experts on this subject based on the ideXlab platform.
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a gene for episodic ataxia Myokymia maps to chromosome 12p13
American Journal of Human Genetics, 1994Co-Authors: M. Litt, Patricia L Kramer, D Root, Stephen T Gancher, D. L. Browne, E R P Brunt, T Phromchotikul, C J Dubay, John G NuttAbstract:Episodic ataxia (EA) is a rare, familial disorder producing attacks of generalized ataxia, with normal or near-normal neurological function between attacks. Families with autosomal dominant EA represent at least two distinct clinical syndromes. One clinical type of EA (MIM 160120) includes individuals who have episodes of ataxia and dysarthria lasting seconds to minutes. In addition, Myokymia (rippling of muscles, diagnosable by electromyography) is evident during and between attacks. Since K+ channel genes are candidate genes for EA, we tested markers near known K+ channel genes for linkage. Using a group of Genethon markers from one such region--chromosome 12p--we found evidence of linkage in four EA/Myokymia families. A maximum combined lod score of 13.6 was obtained at theta = 0, with the marker D12S99. A human Ca++ channel gene, CACNL1A1, and three human K+ channel genes--KCNA5, KCNA6, and KCNA1--map close to D12S99, but the Ca++ channel gene is unlikely to be the site of the defect, because crossovers have been observed to occur between the disease gene and a CA-repeat marker located close to this gene. Studies of a large EA family with a different clinical phenotype (MIM 108500), which lacks Myokymia but is associated with nystagmus, have excluded the gene causing that disease from the chromosome 12p locus.
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episodic ataxia Myokymia syndrome is associated with point mutations in the human potassium channel gene kcna1
Nature Genetics, 1994Co-Authors: D. L. Browne, Patricia L Kramer, Stephen T Gancher, E R P Brunt, John G Nutt, Eric A Smith, M. LittAbstract:Episodic ataxia (EA) is a rare, familial disorder producing attacks of generalized ataxia, with normal or near-normal neurological function between attacks. One type of EA is characterized by brief episodes of ataxia with Myokymia (rippling of muscles) evident between attacks. Linkage studies in four such families suggested localization of an EA/Myokymia gene near the voltage gated K+ channel gene, KCNA1 (Kv1.1), on chromosome 12p. Mutation analysis of the KCNA1 coding region in these families identified four different missense point mutations present in the heterozygous state, indicating that EA/Myokymia can result from mutations in this gene.
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episodic ataxia Myokymia syndrome is associated with point mutations in the human potassium channel gene kcna1 kv1 1
American Journal of Human Genetics, 1994Co-Authors: D. L. Browne, Stephen T Gancher, John G NuttAbstract:Episodic ataxia (EA) is a rare, familial disorder producing attacks of generalized ataxia, with normal or near-normal neurological function between attacks. One type of EA (MIM No.160120) displays autosomal dominant inheritance and is characterized by episodes of ataxia lasting seconds to minutes with Myokymia (rippling of small muscles) evident between attacks. Genetic linkage studies in 4 families suggested localization of an EA/Myokymia gene near the K{sup +} channel gene KCNA1 (Kv1.1) on chromosome 12p. Chemical cleavage mismatch and DNA sequence analysis of the KCNA1 coding region in these families identified 4 different missense point mutations present in the heterozygous state. The mutations found were Val174Phe, Arg239Ser, Phe249Ile and Val408Ala; the residue numbers correspond to those in the published amino acid sequence of KCNA1 (Genbank Accession No. L02750). Each of these mutations affects an amino acid residue that is invariant among Drosophila melanogaster, mouse, rat and human, The mutations were present in the affected members of the family and absent in all of the unaffected members and in at least 70 unrelated control individuals. These data strongly suggest that EA/Myokymia can result from mutations in the KCNA1 gene.
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A GENE FOR EPISODIC ATAXIA/Myokymia MAPS TO CHROMOSOME 12P13
American journal of human genetics, 1994Co-Authors: M. Litt, D. L. Browne, E R P Brunt, T Phromchotikul, C J Dubay, John G NuttAbstract:Episodic ataxia (EA) is a rare, familial disorder producing attacks of generalized ataxia, with normal or near-normal neurological function between attacks. Families with autosomal dominant EA represent at least two distinct clinical syndromes. One clinical type of EA (MIM 160120) includes individuals who have episodes of ataxia and dysarthria lasting seconds to minutes. In addition, Myokymia (rippling of muscles, diagnosable by electromyography) is evident during and between attacks. Since K+ channel genes are candidate genes for EA, we tested markers near known K+ channel genes for linkage. Using a group of Genethon markers from one such region--chromosome 12p--we found evidence of linkage in four EA/Myokymia families. A maximum combined lod score of 13.6 was obtained at theta = 0, with the marker D12S99. A human Ca++ channel gene, CACNL1A1, and three human K+ channel genes--KCNA5, KCNA6, and KCNA1--map close to D12S99, but the Ca++ channel gene is unlikely to be the site of the defect, because crossovers have been observed to occur between the disease gene and a CA-repeat marker located close to this gene. Studies of a large EA family with a different clinical phenotype (MIM 108500), which lacks Myokymia but is associated with nystagmus, have excluded the gene causing that disease from the chromosome 12p locus.
D. L. Browne - One of the best experts on this subject based on the ideXlab platform.
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Hereditary Myokymia and paroxysmal ataxia linked to chromosome 12 is responsive to acetazolamide.
Journal of neurology neurosurgery and psychiatry, 1995Co-Authors: W. J. Lubbers, Ewout R. Brunt, Hans Scheffer, M. Litt, R. Stulp, D. L. Browne, T.w. Van WeerdenAbstract:A sixth family with autosomal dominantly inherited Myokymia and paroxysmal ataxia is described. The syndrome in this family is linked to the recently discovered locus for inherited Myokymia and paroxysmal ataxia on the human chromosome 12p, and a missense mutation is shown in the KCNA1 gene. The attacks of ataxia in this family compare well with those of previously described families and similarly are precipitated by kinesigenic stimuli, exertion, and startle. Responsiveness of these attacks to low dose acetazolamide is confirmed, but some loss of efficacy occurs with prolonged treatment, and side effects are notable. Although not all affected family members showed Myokymia on clinical examination, electromyography invariably showed myokymic discharges, in one patient only after a short provocation with regional ischaemia. One affected family member also had attacks of paroxysmal kinesigenic choreoathetosis, responsive to carbamazepine.
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a gene for episodic ataxia Myokymia maps to chromosome 12p13
American Journal of Human Genetics, 1994Co-Authors: M. Litt, Patricia L Kramer, D Root, Stephen T Gancher, D. L. Browne, E R P Brunt, T Phromchotikul, C J Dubay, John G NuttAbstract:Episodic ataxia (EA) is a rare, familial disorder producing attacks of generalized ataxia, with normal or near-normal neurological function between attacks. Families with autosomal dominant EA represent at least two distinct clinical syndromes. One clinical type of EA (MIM 160120) includes individuals who have episodes of ataxia and dysarthria lasting seconds to minutes. In addition, Myokymia (rippling of muscles, diagnosable by electromyography) is evident during and between attacks. Since K+ channel genes are candidate genes for EA, we tested markers near known K+ channel genes for linkage. Using a group of Genethon markers from one such region--chromosome 12p--we found evidence of linkage in four EA/Myokymia families. A maximum combined lod score of 13.6 was obtained at theta = 0, with the marker D12S99. A human Ca++ channel gene, CACNL1A1, and three human K+ channel genes--KCNA5, KCNA6, and KCNA1--map close to D12S99, but the Ca++ channel gene is unlikely to be the site of the defect, because crossovers have been observed to occur between the disease gene and a CA-repeat marker located close to this gene. Studies of a large EA family with a different clinical phenotype (MIM 108500), which lacks Myokymia but is associated with nystagmus, have excluded the gene causing that disease from the chromosome 12p locus.
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episodic ataxia Myokymia syndrome is associated with point mutations in the human potassium channel gene kcna1
Nature Genetics, 1994Co-Authors: D. L. Browne, Patricia L Kramer, Stephen T Gancher, E R P Brunt, John G Nutt, Eric A Smith, M. LittAbstract:Episodic ataxia (EA) is a rare, familial disorder producing attacks of generalized ataxia, with normal or near-normal neurological function between attacks. One type of EA is characterized by brief episodes of ataxia with Myokymia (rippling of muscles) evident between attacks. Linkage studies in four such families suggested localization of an EA/Myokymia gene near the voltage gated K+ channel gene, KCNA1 (Kv1.1), on chromosome 12p. Mutation analysis of the KCNA1 coding region in these families identified four different missense point mutations present in the heterozygous state, indicating that EA/Myokymia can result from mutations in this gene.
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episodic ataxia Myokymia syndrome is associated with point mutations in the human potassium channel gene kcna1 kv1 1
American Journal of Human Genetics, 1994Co-Authors: D. L. Browne, Stephen T Gancher, John G NuttAbstract:Episodic ataxia (EA) is a rare, familial disorder producing attacks of generalized ataxia, with normal or near-normal neurological function between attacks. One type of EA (MIM No.160120) displays autosomal dominant inheritance and is characterized by episodes of ataxia lasting seconds to minutes with Myokymia (rippling of small muscles) evident between attacks. Genetic linkage studies in 4 families suggested localization of an EA/Myokymia gene near the K{sup +} channel gene KCNA1 (Kv1.1) on chromosome 12p. Chemical cleavage mismatch and DNA sequence analysis of the KCNA1 coding region in these families identified 4 different missense point mutations present in the heterozygous state. The mutations found were Val174Phe, Arg239Ser, Phe249Ile and Val408Ala; the residue numbers correspond to those in the published amino acid sequence of KCNA1 (Genbank Accession No. L02750). Each of these mutations affects an amino acid residue that is invariant among Drosophila melanogaster, mouse, rat and human, The mutations were present in the affected members of the family and absent in all of the unaffected members and in at least 70 unrelated control individuals. These data strongly suggest that EA/Myokymia can result from mutations in the KCNA1 gene.
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A GENE FOR EPISODIC ATAXIA/Myokymia MAPS TO CHROMOSOME 12P13
American journal of human genetics, 1994Co-Authors: M. Litt, D. L. Browne, E R P Brunt, T Phromchotikul, C J Dubay, John G NuttAbstract:Episodic ataxia (EA) is a rare, familial disorder producing attacks of generalized ataxia, with normal or near-normal neurological function between attacks. Families with autosomal dominant EA represent at least two distinct clinical syndromes. One clinical type of EA (MIM 160120) includes individuals who have episodes of ataxia and dysarthria lasting seconds to minutes. In addition, Myokymia (rippling of muscles, diagnosable by electromyography) is evident during and between attacks. Since K+ channel genes are candidate genes for EA, we tested markers near known K+ channel genes for linkage. Using a group of Genethon markers from one such region--chromosome 12p--we found evidence of linkage in four EA/Myokymia families. A maximum combined lod score of 13.6 was obtained at theta = 0, with the marker D12S99. A human Ca++ channel gene, CACNL1A1, and three human K+ channel genes--KCNA5, KCNA6, and KCNA1--map close to D12S99, but the Ca++ channel gene is unlikely to be the site of the defect, because crossovers have been observed to occur between the disease gene and a CA-repeat marker located close to this gene. Studies of a large EA family with a different clinical phenotype (MIM 108500), which lacks Myokymia but is associated with nystagmus, have excluded the gene causing that disease from the chromosome 12p locus.
M. Litt - One of the best experts on this subject based on the ideXlab platform.
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Hereditary Myokymia and paroxysmal ataxia linked to chromosome 12 is responsive to acetazolamide.
Journal of neurology neurosurgery and psychiatry, 1995Co-Authors: W. J. Lubbers, Ewout R. Brunt, Hans Scheffer, M. Litt, R. Stulp, D. L. Browne, T.w. Van WeerdenAbstract:A sixth family with autosomal dominantly inherited Myokymia and paroxysmal ataxia is described. The syndrome in this family is linked to the recently discovered locus for inherited Myokymia and paroxysmal ataxia on the human chromosome 12p, and a missense mutation is shown in the KCNA1 gene. The attacks of ataxia in this family compare well with those of previously described families and similarly are precipitated by kinesigenic stimuli, exertion, and startle. Responsiveness of these attacks to low dose acetazolamide is confirmed, but some loss of efficacy occurs with prolonged treatment, and side effects are notable. Although not all affected family members showed Myokymia on clinical examination, electromyography invariably showed myokymic discharges, in one patient only after a short provocation with regional ischaemia. One affected family member also had attacks of paroxysmal kinesigenic choreoathetosis, responsive to carbamazepine.
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a gene for episodic ataxia Myokymia maps to chromosome 12p13
American Journal of Human Genetics, 1994Co-Authors: M. Litt, Patricia L Kramer, D Root, Stephen T Gancher, D. L. Browne, E R P Brunt, T Phromchotikul, C J Dubay, John G NuttAbstract:Episodic ataxia (EA) is a rare, familial disorder producing attacks of generalized ataxia, with normal or near-normal neurological function between attacks. Families with autosomal dominant EA represent at least two distinct clinical syndromes. One clinical type of EA (MIM 160120) includes individuals who have episodes of ataxia and dysarthria lasting seconds to minutes. In addition, Myokymia (rippling of muscles, diagnosable by electromyography) is evident during and between attacks. Since K+ channel genes are candidate genes for EA, we tested markers near known K+ channel genes for linkage. Using a group of Genethon markers from one such region--chromosome 12p--we found evidence of linkage in four EA/Myokymia families. A maximum combined lod score of 13.6 was obtained at theta = 0, with the marker D12S99. A human Ca++ channel gene, CACNL1A1, and three human K+ channel genes--KCNA5, KCNA6, and KCNA1--map close to D12S99, but the Ca++ channel gene is unlikely to be the site of the defect, because crossovers have been observed to occur between the disease gene and a CA-repeat marker located close to this gene. Studies of a large EA family with a different clinical phenotype (MIM 108500), which lacks Myokymia but is associated with nystagmus, have excluded the gene causing that disease from the chromosome 12p locus.
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episodic ataxia Myokymia syndrome is associated with point mutations in the human potassium channel gene kcna1
Nature Genetics, 1994Co-Authors: D. L. Browne, Patricia L Kramer, Stephen T Gancher, E R P Brunt, John G Nutt, Eric A Smith, M. LittAbstract:Episodic ataxia (EA) is a rare, familial disorder producing attacks of generalized ataxia, with normal or near-normal neurological function between attacks. One type of EA is characterized by brief episodes of ataxia with Myokymia (rippling of muscles) evident between attacks. Linkage studies in four such families suggested localization of an EA/Myokymia gene near the voltage gated K+ channel gene, KCNA1 (Kv1.1), on chromosome 12p. Mutation analysis of the KCNA1 coding region in these families identified four different missense point mutations present in the heterozygous state, indicating that EA/Myokymia can result from mutations in this gene.
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A GENE FOR EPISODIC ATAXIA/Myokymia MAPS TO CHROMOSOME 12P13
American journal of human genetics, 1994Co-Authors: M. Litt, D. L. Browne, E R P Brunt, T Phromchotikul, C J Dubay, John G NuttAbstract:Episodic ataxia (EA) is a rare, familial disorder producing attacks of generalized ataxia, with normal or near-normal neurological function between attacks. Families with autosomal dominant EA represent at least two distinct clinical syndromes. One clinical type of EA (MIM 160120) includes individuals who have episodes of ataxia and dysarthria lasting seconds to minutes. In addition, Myokymia (rippling of muscles, diagnosable by electromyography) is evident during and between attacks. Since K+ channel genes are candidate genes for EA, we tested markers near known K+ channel genes for linkage. Using a group of Genethon markers from one such region--chromosome 12p--we found evidence of linkage in four EA/Myokymia families. A maximum combined lod score of 13.6 was obtained at theta = 0, with the marker D12S99. A human Ca++ channel gene, CACNL1A1, and three human K+ channel genes--KCNA5, KCNA6, and KCNA1--map close to D12S99, but the Ca++ channel gene is unlikely to be the site of the defect, because crossovers have been observed to occur between the disease gene and a CA-repeat marker located close to this gene. Studies of a large EA family with a different clinical phenotype (MIM 108500), which lacks Myokymia but is associated with nystagmus, have excluded the gene causing that disease from the chromosome 12p locus.
Stephen T Gancher - One of the best experts on this subject based on the ideXlab platform.
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episodic ataxia Myokymia syndrome is associated with point mutations in the human potassium channel gene kcna1
Nature Genetics, 1994Co-Authors: D. L. Browne, Patricia L Kramer, Stephen T Gancher, E R P Brunt, John G Nutt, Eric A Smith, M. LittAbstract:Episodic ataxia (EA) is a rare, familial disorder producing attacks of generalized ataxia, with normal or near-normal neurological function between attacks. One type of EA is characterized by brief episodes of ataxia with Myokymia (rippling of muscles) evident between attacks. Linkage studies in four such families suggested localization of an EA/Myokymia gene near the voltage gated K+ channel gene, KCNA1 (Kv1.1), on chromosome 12p. Mutation analysis of the KCNA1 coding region in these families identified four different missense point mutations present in the heterozygous state, indicating that EA/Myokymia can result from mutations in this gene.
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a gene for episodic ataxia Myokymia maps to chromosome 12p13
American Journal of Human Genetics, 1994Co-Authors: M. Litt, Patricia L Kramer, D Root, Stephen T Gancher, D. L. Browne, E R P Brunt, T Phromchotikul, C J Dubay, John G NuttAbstract:Episodic ataxia (EA) is a rare, familial disorder producing attacks of generalized ataxia, with normal or near-normal neurological function between attacks. Families with autosomal dominant EA represent at least two distinct clinical syndromes. One clinical type of EA (MIM 160120) includes individuals who have episodes of ataxia and dysarthria lasting seconds to minutes. In addition, Myokymia (rippling of muscles, diagnosable by electromyography) is evident during and between attacks. Since K+ channel genes are candidate genes for EA, we tested markers near known K+ channel genes for linkage. Using a group of Genethon markers from one such region--chromosome 12p--we found evidence of linkage in four EA/Myokymia families. A maximum combined lod score of 13.6 was obtained at theta = 0, with the marker D12S99. A human Ca++ channel gene, CACNL1A1, and three human K+ channel genes--KCNA5, KCNA6, and KCNA1--map close to D12S99, but the Ca++ channel gene is unlikely to be the site of the defect, because crossovers have been observed to occur between the disease gene and a CA-repeat marker located close to this gene. Studies of a large EA family with a different clinical phenotype (MIM 108500), which lacks Myokymia but is associated with nystagmus, have excluded the gene causing that disease from the chromosome 12p locus.
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a gene for nystagmus associated episodic ataxia maps to chromosome 19p
American Journal of Human Genetics, 1994Co-Authors: Patricia L Kramer, D Root, Stephen T GancherAbstract:Episodic ataxia (EA) is a rare, autosomal dominant disorder, characterized by attacks of generalized ataxia and relatively normal neurological function between attacks. Onset occurs in childhood or adolescence and persists through adulthood. Penetrance is nearly complete. EA is clinically heterogeneous, including at least two distinct entities: (1) episodes of ataxia and dysarthria lasting hours to days, generally with interictal nystagmus (MIM 108500); (2) episodes of ataxia and dysarthria lasting only minutes, with interictal Myokymia (MMM 160120). The EA/nystagmus patients sometimes develop persistent ataxia and cerebellar atrophy. Previously we reported linkage in four EA/Myokymia families to a K{sup +} channel gene on chromosome 12p. We excluded this region in a large family with EA/nystagmus. We now report evidence for linkage to chromosome 19p in this and in one other EA/nystagmus family, based on eight microsatellite markers which span approximately 30 cM. The region is flanked distally by D19S209 and proximally by D19S226. All six markers within this region gave positive evidence for linkage; the highest total two-point lod scores occurred wtih D19S221 (3.98 at theta = 0.10) and D19S413 (3.37 at theta = 0.05). Interestingly, Joutel et al. (1993) mapped a gene for familial hemiplegic migraine (FHM) to the region aroundmore » D19S221. Some individuals in these families have ataxia, cerebellar atrophy and interictal nystagmus, but no episodic ataxia. These results demonstrate that the clinical heterogeneity in EA reflects underlying genetic hetreogeneity. In addition, they suggest that EA/nystagmus and some FHM may represent different mutations in the same gene locus on chromosome 19p.« less
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episodic ataxia Myokymia syndrome is associated with point mutations in the human potassium channel gene kcna1 kv1 1
American Journal of Human Genetics, 1994Co-Authors: D. L. Browne, Stephen T Gancher, John G NuttAbstract:Episodic ataxia (EA) is a rare, familial disorder producing attacks of generalized ataxia, with normal or near-normal neurological function between attacks. One type of EA (MIM No.160120) displays autosomal dominant inheritance and is characterized by episodes of ataxia lasting seconds to minutes with Myokymia (rippling of small muscles) evident between attacks. Genetic linkage studies in 4 families suggested localization of an EA/Myokymia gene near the K{sup +} channel gene KCNA1 (Kv1.1) on chromosome 12p. Chemical cleavage mismatch and DNA sequence analysis of the KCNA1 coding region in these families identified 4 different missense point mutations present in the heterozygous state. The mutations found were Val174Phe, Arg239Ser, Phe249Ile and Val408Ala; the residue numbers correspond to those in the published amino acid sequence of KCNA1 (Genbank Accession No. L02750). Each of these mutations affects an amino acid residue that is invariant among Drosophila melanogaster, mouse, rat and human, The mutations were present in the affected members of the family and absent in all of the unaffected members and in at least 70 unrelated control individuals. These data strongly suggest that EA/Myokymia can result from mutations in the KCNA1 gene.
Patricia L Kramer - One of the best experts on this subject based on the ideXlab platform.
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episodic ataxia Myokymia syndrome is associated with point mutations in the human potassium channel gene kcna1
Nature Genetics, 1994Co-Authors: D. L. Browne, Patricia L Kramer, Stephen T Gancher, E R P Brunt, John G Nutt, Eric A Smith, M. LittAbstract:Episodic ataxia (EA) is a rare, familial disorder producing attacks of generalized ataxia, with normal or near-normal neurological function between attacks. One type of EA is characterized by brief episodes of ataxia with Myokymia (rippling of muscles) evident between attacks. Linkage studies in four such families suggested localization of an EA/Myokymia gene near the voltage gated K+ channel gene, KCNA1 (Kv1.1), on chromosome 12p. Mutation analysis of the KCNA1 coding region in these families identified four different missense point mutations present in the heterozygous state, indicating that EA/Myokymia can result from mutations in this gene.
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a gene for episodic ataxia Myokymia maps to chromosome 12p13
American Journal of Human Genetics, 1994Co-Authors: M. Litt, Patricia L Kramer, D Root, Stephen T Gancher, D. L. Browne, E R P Brunt, T Phromchotikul, C J Dubay, John G NuttAbstract:Episodic ataxia (EA) is a rare, familial disorder producing attacks of generalized ataxia, with normal or near-normal neurological function between attacks. Families with autosomal dominant EA represent at least two distinct clinical syndromes. One clinical type of EA (MIM 160120) includes individuals who have episodes of ataxia and dysarthria lasting seconds to minutes. In addition, Myokymia (rippling of muscles, diagnosable by electromyography) is evident during and between attacks. Since K+ channel genes are candidate genes for EA, we tested markers near known K+ channel genes for linkage. Using a group of Genethon markers from one such region--chromosome 12p--we found evidence of linkage in four EA/Myokymia families. A maximum combined lod score of 13.6 was obtained at theta = 0, with the marker D12S99. A human Ca++ channel gene, CACNL1A1, and three human K+ channel genes--KCNA5, KCNA6, and KCNA1--map close to D12S99, but the Ca++ channel gene is unlikely to be the site of the defect, because crossovers have been observed to occur between the disease gene and a CA-repeat marker located close to this gene. Studies of a large EA family with a different clinical phenotype (MIM 108500), which lacks Myokymia but is associated with nystagmus, have excluded the gene causing that disease from the chromosome 12p locus.
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a gene for nystagmus associated episodic ataxia maps to chromosome 19p
American Journal of Human Genetics, 1994Co-Authors: Patricia L Kramer, D Root, Stephen T GancherAbstract:Episodic ataxia (EA) is a rare, autosomal dominant disorder, characterized by attacks of generalized ataxia and relatively normal neurological function between attacks. Onset occurs in childhood or adolescence and persists through adulthood. Penetrance is nearly complete. EA is clinically heterogeneous, including at least two distinct entities: (1) episodes of ataxia and dysarthria lasting hours to days, generally with interictal nystagmus (MIM 108500); (2) episodes of ataxia and dysarthria lasting only minutes, with interictal Myokymia (MMM 160120). The EA/nystagmus patients sometimes develop persistent ataxia and cerebellar atrophy. Previously we reported linkage in four EA/Myokymia families to a K{sup +} channel gene on chromosome 12p. We excluded this region in a large family with EA/nystagmus. We now report evidence for linkage to chromosome 19p in this and in one other EA/nystagmus family, based on eight microsatellite markers which span approximately 30 cM. The region is flanked distally by D19S209 and proximally by D19S226. All six markers within this region gave positive evidence for linkage; the highest total two-point lod scores occurred wtih D19S221 (3.98 at theta = 0.10) and D19S413 (3.37 at theta = 0.05). Interestingly, Joutel et al. (1993) mapped a gene for familial hemiplegic migraine (FHM) to the region aroundmore » D19S221. Some individuals in these families have ataxia, cerebellar atrophy and interictal nystagmus, but no episodic ataxia. These results demonstrate that the clinical heterogeneity in EA reflects underlying genetic hetreogeneity. In addition, they suggest that EA/nystagmus and some FHM may represent different mutations in the same gene locus on chromosome 19p.« less
