Ra. Ophoff et al., A 3-MB REGION FOR THE FAMILIAL HEMIPLEGIC MIGRAINE LOCUS ON 19P13.1-P13.2 - EXCLUSION OF PRKCSH AS A CANDIDATE GENE, European journal of human genetics, 4(6), 1996, pp. 321-328
Familial hemiplegic migraine (FHM) is an autosomal dominant subtype of
migraine with attacks, associated with transient episodes of hemipare
sis. One of the genes for FHM has been assigned to chromosome 19p13. D
etailed analysis of critical recombinants from two different chromosom
e 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 a
lso been linked to the same chromosomal region. Most of the interval w
as completely covered by YAC and cosmid contigs; the physical map yiel
ded approximately 3 Mb encompassing several genes including the protei
n kinase substrate 80K-H (PRKCSH) gene. Since PRKCSH is involved in ne
uronal signal transduction, it was considered to be an FHM candidate g
ene. The genomic structure of this gene was established and mutation a
nalysis for all exon and flanking intron sequences was performed in FH
M- and EA-2-affected individuals. Five polymorphisms were identified,
including a trinucleotide repeat length variation in the coding sequen
ce. However, no potential disease causing mutation was found and there
fore the PRKCSH gene can be excluded for both FHM and EA-2.