A 3-Mb region for the familial hemiplegic migraine locus on 19p13.1-p13.2: exclusion of PRKCSH as a candidate gene. Dutch Migraine Genetic Research Group.
Familial hemiplegic migraine (FHM) is an autosomal domianant subtype of migraine with attacks, associated with transient episodes of hemiparesis. One of the genes for FHM has been assigned to chromosome 19p13. Detailed analysis of critical recombinants from two different chromosome 19-linked FHM families, using new markers indicated a 6-cM candidate region on 19p13.1-p13.2 flanked by loci D19S394 and D19S226. Another paroxysmal neurological disorder, episodic ataxia type 2 (EA-2), has also been linked to the same chromosomal region. Most of the interval was completely covered by YAC and cosmid contigs; the physical map yielded approximately 3 Mb encompassing several genes including the protein kinase substrate 80K-H (PRKCSH) gene. Since PRKCSH is involved in neuronal signal transduction, it was considered to be an FHM candidate gene. The genomic structure of this gene was established and mutation analysis for all exon and flanking intron sequences was performed in FHM- and EA-2-affected individuals. Five polymorphisms were identified, including a trinucleotide repeat length variation in the coding sequence. However, no potential disease causing mutation was found and therefore the PRKCSH gene can be excluded for both FHM and EA-2.
Ophoff
R A
RA
MGC Department of Human Genetics, Leiden University, The Netherlands.
Terwindt
G M
GM
Vergouwe
M N
MN
van Eijk
R
R
Mohrenweiser
H
H
Litt
M
M
Hofker
M H
MH
Haan
J
J
Ferrari
M D
MD
Frants
R R
RR
D001483:Base Sequence; D002135:Calcium-Binding Proteins; D002874:Chromosome Mapping; D002888:Chromosomes, Human, Pair 19; D004252:DNA Mutational Analysis; D018076:DNA, Complementary; D005091:Exons; D005959:Glucosidases; D006429:Hemiplegia / Q000150:complications / Q000235:genetics*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D007438:Introns; D008565:Membrane Proteins; D008881:Migraine Disorders / Q000150:complications / Q000235:genetics*; D008969:Molecular Sequence Data; D000076250:Myristoylated Alanine-Rich C Kinase Substrate; D010750:Phosphoproteins / Q000235:genetics*
D002135:Calcium-Binding Proteins; D018076:DNA, Complementary; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D010750:Phosphoproteins; D000076250:Myristoylated Alanine-Rich C Kinase Substrate; D005959:Glucosidases; C070368:PRKCSH protein, human