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Familial hemiplegic migraine: linkage to chromosome 14q32 in a Spanish kindred

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Abstract

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.

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Acknowledgements

This study was supported by grants from Ministerio de Educación y Ciencia SAF 2003/04704, SAF2006-13893-C02-01, Fundació La Marató de TV3 061330 and AGAUR 2005SGR00848, Spain. E.C.-L. is funded by Ministerio de Educación y Ciencia and R.C. by Institut de Recerca Vall d’Hebron, Spain. M.B. and M.M. are recipients of a Ramon y Cajal and a Juan de la Cierva contracts from Ministerio de Ciencia e Innovación, Spain, respectively. The authors declare that the experiments described in this work comply with the current laws of Spain.

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Authors and Affiliations

  1. 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

    Ester Cuenca-León, Roser Corominas, Manuel Roig & Alfons Macaya

  2. Genes and Disease Program, CRG, UPF, CIBERESP, CeGen, Barcelona, Spain

    Magda Montfort & Mònica Bayés

  3. Corporació Sanitària Parc Taulí, Sabadell, Spain

    Josep Artigas

  4. Departament de Genètica, Universitat de Barcelona, CIBERER, IBUB, Barcelona, Spain

    Bru Cormand

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  1. Ester Cuenca-León
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  2. Roser Corominas
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Correspondence to Alfons Macaya.

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Fig. S1

Exclusion of previously reported migraine loci by multipoint parametric linkage analysis using LINKMAP and assuming autosomal dominant inheritance, a penetrance of 95% and a phenocopy rate of 1%. The order of and distances between the microsatellite markers studied are 1q21–23 (D1S1675—10.58 cM—GATA13C08—1.27 cM—D1S1595—14.57 cM—D1S1677), 1q31–32 (D1S1660—6.02 cM—D1S1678—7.70 cM—D1S1663—7.22 cM—D1S2141), 4q24 (D4S2409—4.59 cM—D4S2380—4.19 cM—D4S1647—3.01 cM—D4S1572), 6p12.2 (D6S1650—4.48 cM—D6S452—4.65 cM—D6S466) and 14q21.2–22.3 (D14S288—5.68 cM—D14S978—3.17 cM—D14S276—4.07 cM—D14S980) according to the Marshfield genetic map (http://research.marshfieldclinic.org/genetics). The 19p13 locus containing the CACNA1A gene was excluded using the microsatellite marker GATA134B01 by two-point linkage analysis with Z = 3.9 at θ = 0.0 (MLINK) (PDF 563 kb)

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Cuenca-León, E., Corominas, R., Montfort, M. et al. Familial hemiplegic migraine: linkage to chromosome 14q32 in a Spanish kindred. Neurogenetics 10, 191–198 (2009). https://doi.org/10.1007/s10048-008-0169-6

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