Familial hemiplegic migraine: linkage to chromosome 14q32 in a Spanish kindred.
We sought to map the disease-causing gene in a large Spanish kindred with familial hemiplegic migraine (FHM). Patients were classified according to the ICHD-II criteria. After ruling out linkage to known migraine genetic loci, a single nucleotide polymorphism-based, 0.62-cM density genome-wide scan was performed. Among 13 affected subjects, FHM was the prevailing migraine phenotype in six, migraine with aura in four and migraine without aura in three. Linkage analysis revealed a disease locus in a 4.15-Mb region on 14q32 with a maximum two-point logarithm of odds (LOD) score of 3.1 and a multipoint parametric LOD score of 3.8. This genomic region does not overlap with the reported migraine loci on 14q21-22. Sequence analysis of three candidate genes in the region, SLC24A4, ATXN3 and ITPK1, failed to show disease-causing mutations in our patients. Genetic heterogeneity in FHM may be greater than previously suspected.
Cuenca-León
Ester
E
Grup de Recerca en Neurologia Infantil i Psiquiatria Genètica, Institut de Recerca Hospital Universitari Vall d'Hebron, Pg. Vall d'Hebron 119-129, 08035 Barcelona, Spain.
Corominas
Roser
R
Montfort
Magda
M
Artigas
Josep
J
Roig
Manuel
M
Bayés
Mònica
M
Cormand
Bru
B
Macaya
Alfons
A
D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D002883:Chromosomes, Human, Pair 14; D004252:DNA Mutational Analysis; D005260:Female; D018740:Genetic Heterogeneity; D008040:Genetic Linkage; D020022:Genetic Predisposition to Disease; D015894:Genome, Human; D055106:Genome-Wide Association Study; D006801:Humans; D008126:Lod Score; D008297:Male; D020325:Migraine with Aura / Q000235:genetics*; D010375:Pedigree; D020641:Polymorphism, Single Nucleotide; D013030:Spain