Top

Published in:

01-07-2009 | Original Article

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

Authors: Ester Cuenca-León, Roser Corominas, Magda Montfort, Josep Artigas, Manuel Roig, Mònica Bayés, Bru Cormand, Alfons Macaya

Published in: Neurogenetics | Issue 3/2009

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.

Available only for authorised users

International Headache Society (2004) The International Classification of Headache Disorders: 2nd edition. Cephalalgia 24(Suppl 1):9–160. doi:10.1111/j.1468-2982.2003.00824.x

Abecasis GR, Cherny SS, Cookson WO, Cardon LR (2002) Merlin—rapid analysis of dense genetic maps using sparse gene flow trees. Nat Genet 30:97–101. doi:10.1038/ng786 PubMedCrossRef

Bjornsson A, Gudmundsson G, Gudfinnsson E, Hrafnsdottir M, Benedikz J, Skuladottir S, Kristjansson K, Frigge ML, Kong A, Stefansson K, Gulcher JR (2003) Localization of a gene for migraine without aura to chromosome 4q21. Am J Hum Genet 73:986–993. doi:10.1086/378417 PubMedCrossRef

Cader ZM, Noble-Topham S, Dyment DA, Cherny SS, Brown JD, Rice GP, Ebers GC (2003) Significant linkage to migraine with aura on chromosome 11q24. Hum Mol Genet 12:2511–2517. doi:10.1093/hmg/ddg252 PubMedCrossRef

Carlsson A, Forsgren L, Nylander PO, Hellman U, Forsman-Semb K, Holmgren G, Holmberg D, Holmberg M (2002) Identification of a susceptibility locus for migraine with and without aura on 6p12.2–p21.1. Neurology 59:1804–1807PubMedCrossRef

Cottingham RW Jr, Idury RM, Schaffer AA (1993) Faster sequential genetic linkage computations. Am J Hum Genet 53:252–263PubMed

Cuenca-Leon E, Corominas R, Fernandez-Castillo N, Volpini V, Del Toro M, Roig M, Macaya A, Cormand B (2008) Genetic analysis of 27 Spanish patients with hemiplegic migraine, basilar-type migraine and childhood periodic syndromes. Cephalalgia 28:1039–1047. doi:10.1111/j.1468-2982.2008.01645.x PubMedCrossRef

De Fusco M, Marconi R, Silvestri L, Atorino L, Rampoldi L, Morgante L, Ballabio A, Aridon P, Casari G (2003) Haploinsufficiency of ATP1A2 encoding the Na+/K+ pump alpha2 subunit associated with familial hemiplegic migraine type 2. Nat Genet 33:192–196. doi:10.1038/ng1081 PubMedCrossRef

Deprez L, Peeters K, Van Paesschen W, Claeys KG, Claes LR, Suls A, Audenaert D, Van Dyck T, Goossens D, Del-Favero J, De Jonghe P (2007) Familial occipitotemporal lobe epilepsy and migraine with visual aura: linkage to chromosome 9q. Neurology 68:1995–2002. doi:10.1212/01.wnl.0000262764.78511.17 PubMedCrossRef

10.

Dichgans M, Freilinger T, Eckstein G, Babini E, Lorenz-Depiereux B, Biskup S, Ferrari MD, Herzog J, van den Maagdenberg AM, Pusch M, Strom TM (2005) Mutation in the neuronal voltage-gated sodium channel SCN1A in familial hemiplegic migraine. Lancet 366:371–377. doi:10.1016/S0140-6736(05)66786-4 PubMedCrossRef

11.

Ducros A, Denier C, Joutel A, Cecillon M, Lescoat C, Vahedi K, Darcel F, Vicaut E, Bousser MG, Tournier-Lasserve E (2001) The clinical spectrum of familial hemiplegic migraine associated with mutations in a neuronal calcium channel. N Engl J Med 345:17–24. doi:10.1056/NEJM200107053450103 PubMedCrossRef

12.

Gardner K, Barmada MM, Ptacek LJ, Hoffman EP (1997) A new locus for hemiplegic migraine maps to chromosome 1q31. Neurology 49:1231–1238PubMed

13.

Gargus JJ, Tournay A (2007) Novel mutation confirms seizure locus SCN1A is also familial hemiplegic migraine locus FHM3. Pediatr Neurol 37:407–410. doi:10.1016/j.pediatrneurol.2007.06.016 PubMedCrossRef

14.

Goadsby PJ (2007) Recent advances in understanding migraine mechanisms, molecules and therapeutics. Trends Mol Med 13:39–44. doi:10.1016/j.molmed.2006.11.005 PubMedCrossRef

15.

Jen JC, Kim GW, Dudding KA, Baloh RW (2004) No mutations in CACNA1A and ATP1A2 in probands with common types of migraine. Arch Neurol 61:926–928. doi:10.1001/archneur.61.6.926 PubMedCrossRef

16.

Jen JC, Klein A, Boltshauser E, Cartwright MS, Roach ES, Mamsa H, Baloh RW (2007) Prolonged hemiplegic episodes in children due to mutations in ATP1A2. J Neurol Neurosurg Psychiatry 78:523–526. doi:10.1136/jnnp.2006.103267 PubMedCrossRef

17.

Kawaguchi Y, Okamoto T, Taniwaki M, Aizawa M, Inoue M, Katayama S, Kawakami H, Nakamura S, Nishimura M, Akiguchi I et al (1994) CAG expansions in a novel gene for Machado–Joseph disease at chromosome 14q32.1. Nat Genet 8:221–228. doi:10.1038/ng1194-221 PubMedCrossRef

18.

Lea RA, Curtain RP, Hutchins C, Brimage PJ, Griffiths LR (2001) Investigation of the CACNA1A gene as a candidate for typical migraine susceptibility. Am J Med Genet 105:707–712. doi:10.1002/ajmg.1609 PubMedCrossRef

19.

Lea RA, Nyholt DR, Curtain RP, Ovcaric M, Sciascia R, Bellis C, Macmillan J, Quinlan S, Gibson RA, McCarthy LC, Riley JH, Smithies YJ, Kinrade S, Griffiths LR (2005) A genome-wide scan provides evidence for loci influencing a severe heritable form of common migraine. Neurogenetics 6:67–72. doi:10.1007/s10048-005-0215-6 PubMedCrossRef

20.

Marconi R, De Fusco M, Aridon P, Plewnia K, Rossi M, Carapelli S, Ballabio A, Morgante L, Musolino R, Epifanio A, Micieli G, De Michele G, Casari G (2003) Familial hemiplegic migraine type 2 is linked to 0.9 Mb region on chromosome 1q23. Ann Neurol 53:376–381. doi:10.1002/ana.10464 PubMedCrossRef

21.

Nyholt DR, Lea RA, Goadsby PJ, Brimage PJ, Griffiths LR (1998) Familial typical migraine: linkage to chromosome 19p13 and evidence for genetic heterogeneity. Neurology 50:1428–1432PubMed

22.

Nyholt DR, Morley KI, Ferreira MA, Medland SE, Boomsma DI, Heath AC, Merikangas KR, Montgomery GW, Martin NG (2005) Genomewide significant linkage to migrainous headache on chromosome 5q21. Am J Hum Genet 77:500–512. doi:10.1086/444510 PubMedCrossRef

23.

Ophoff RA, Terwindt GM, Vergouwe MN, van Eijk R, Oefner PJ, Hoffman SM, Lamerdin JE, Mohrenweiser HW, Bulman DE, Ferrari M, Haan J, Lindhout D, van Ommen GJ, Hofker MH, Ferrari MD, Frants RR (1996) Familial hemiplegic migraine and episodic ataxia type-2 are caused by mutations in the Ca2+ channel gene CACNL1A4. Cell 87:543–552. doi:10.1016/S0092-8674(00)81373-2 PubMedCrossRef

24.

Ott J (1989) Computer-simulation methods in human linkage analysis. Proc Natl Acad Sci U S A 86:4175–4178. doi:10.1073/pnas.86.11.4175 PubMedCrossRef

25.

Pietrobon D (2007) Familial hemiplegic migraine. Neurotherapeutics 4:274–284. doi:10.1016/j.nurt.2007.01.008 PubMedCrossRef

26.

Russell MB (2008) Is migraine a genetic illness? The various forms of migraine share a common genetic cause. Neurol Sci 29(Suppl 1):S52–S54. doi:10.1007/s10072-008-0887-4 PubMedCrossRef

27.

Soragna D, Vettori A, Carraro G, Marchioni E, Vazza G, Bellini S, Tupler R, Savoldi F, Mostacciuolo ML (2003) A locus for migraine without aura maps on chromosome 14q21.2–q22.3. Am J Hum Genet 72:161–167. doi:10.1086/345298 PubMedCrossRef

28.

Terwilliger JOJ (1994) Handbook of human genetic linkage. The John Hopkins University Press, Baltimore

29.

Terwindt GM, Ophoff RA, Haan J, Vergouwe MN, van Eijk R, Frants RR, Ferrari MD (1998) Variable clinical expression of mutations in the P/Q-type calcium channel gene in familial hemiplegic migraine. Dutch Migraine Genetics Research Group. Neurology 50:1105–1110PubMed

30.

Thomsen LL, Kirchmann M, Bjornsson A, Stefansson H, Jensen RM, Fasquel AC, Petursson H, Stefansson M, Frigge ML, Kong A, Gulcher J, Stefansson K, Olesen J (2007) The genetic spectrum of a population-based sample of familial hemiplegic migraine. Brain 130:346–356. doi:10.1093/brain/awl334 PubMedCrossRef

31.

Thomsen LL, Olesen J (2004) Sporadic hemiplegic migraine. Cephalalgia 24:1016–1023. doi:10.1111/j.1468-2982.2004.00788.x PubMedCrossRef

32.

Tonelli A, Gallanti A, Bersano A, Cardin V, Ballabio E, Airoldi G, Redaelli F, Candelise L, Bresolin N, Bassi MT (2007) Amino acid changes in the amino terminus of the Na,K-adenosine triphosphatase alpha-2 subunit associated to familial and sporadic hemiplegic migraine. Clin Genet 72:517–523PubMedCrossRef

33.

Vanmolkot KR, Babini E, de Vries B, Stam AH, Freilinger T, Terwindt GM, Norris L, Haan J, Frants RR, Ramadan NM, Ferrari MD, Pusch M, van den Maagdenberg AM, Dichgans M (2007) The novel p.L1649Q mutation in the SCN1A epilepsy gene is associated with familial hemiplegic migraine: genetic and functional studies. Mutation in brief #957. Online. Hum Mutat 28:522. doi:10.1002/humu.9486 PubMedCrossRef

34.

Wessman M, Kallela M, Kaunisto MA, Marttila P, Sobel E, Hartiala J, Oswell G, Leal SM, Papp JC, Hamalainen E, Broas P, Joslyn G, Hovatta I, Hiekkalinna T, Kaprio J, Ott J, Cantor RM, Zwart JA, Ilmavirta M, Havanka H, Farkkila M, Peltonen L, Palotie A (2002) A susceptibility locus for migraine with aura, on chromosome 4q24. Am J Hum Genet 70:652–662. doi:10.1086/339078 PubMedCrossRef

35.

Wessman M, Terwindt GM, Kaunisto MA, Palotie A, Ophoff RA (2007) Migraine: a complex genetic disorder. Lancet Neurol 6:521–532. doi:10.1016/S1474-4422(07)70126-6 PubMedCrossRef

36.

Yang XR, Jacobs K, Kerstann KF, Bergen AW, Goldstein AM, Goldin LR (2005) Linkage analysis of the GAW14 simulated dataset with microsatellite and single-nucleotide polymorphism markers in large pedigrees. BMC Genet 6(Suppl 1):S14. doi:10.1186/1471-2156-6-S1-S14 PubMedCrossRef

Title: Familial hemiplegic migraine: linkage to chromosome 14q32 in a Spanish kindred
Authors: Ester Cuenca-León
Roser Corominas
Magda Montfort
Josep Artigas
Manuel Roig
Mònica Bayés
Bru Cormand
Alfons Macaya
Publication date: 01-07-2009
Publisher: Springer-Verlag
Published in: Neurogenetics / Issue 3/2009
Print ISSN: 1364-6745
Electronic ISSN: 1364-6753
DOI: https://doi.org/10.1007/s10048-008-0169-6

Keynote webinar | Spotlight on medication adherence

Springer Medicine

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

Abstract

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 3/2009

A new complex homozygous large rearrangement of the PINK1 gene in a Sudanese family with early onset Parkinson’s disease

Novel mutations in the CDKL5 gene, predicted effects and associated phenotypes

Interaction of the SPG21 protein ACP33/maspardin with the aldehyde dehydrogenase ALDH16A1

Molecular analysis of NPC1 and NPC2 gene in 34 Niemann–Pick C Italian Patients: identification and structural modeling of novel mutations

Whole-genome conditional two-locus analysis identifies novel candidate genes for late-onset Parkinson’s disease

Association between migraine and a functional polymorphism at the dopamine β-hydroxylase locus