Linkage analysis of hemiplegic migraine loci and ChrXq28 in 29 families with familial migraine. P. van Galen1, K. Gardner3, J. Pascual2, M. Barmada1, J. Badger3, M. Soso3, E. Hoffman4. 1) Department of Human Genetics, University of Pittsburgh, PA; 2) Department of Neurology, University Hospital Marques de Valdecilla Santander, Spain; 3) Department of Neurology, University of Pittsburgh, Pittsburgh, PA; 4) Children's National Medical Center,Washington, DC.
Objective: Evaluate familial migraine (with and without aura) for evidence of linkage to the dominant familial hemiplegic migraine (FHM) loci and to a possible X-linked familial migraine locus. Background: Linkage has been previously established for FHM to Chr19p13, Chr1q21-23 and Chr1q31. An X-linked dominant locus spanning a large region around Xq28 has also been suggested for familial migraine. Methods: Probands of 29 migraine families with and without aura were ascertained from Spain (16 families, 69 affected patients) and USA (13 families, 40 affected patients) for a total of 85 sibpairs by neurologists (JP,KG,MS). Additional family members were evaluated directly (Spain) or by questionnaire and clinic or phone interview (USA). DNA was extracted from blood specimens and genotyped with markers D1S422, D1S413, D1S2745, D1S2707, D1S2635, D19S1150, D19S394, DXS1123, DXS1001, DXS1192 and DXS8043 from the four regions using standard PCR, gel electrophoresis and autoradiograms. Alleles were scored, aligned and several different methods of linkage analysis were used, including two-point VITESSE and MMLS with varying penetrance, phenocopy rate and inheritance models; multipoint GENEHUNTER and HOMOG. Results: Of the 29 families evaluated, two point analysis showed a highest LOD of 1.38, theta = 0.0 in a single family for region Chr1q21-23, using a recessive, 50% penetrant model, phenocopy 0%. The highest NPL score for a single family was 1.4 and 1.26, p values 0.043 for markers D1S2635 and D1S2707 at the proximal Chr1q21-23 FHM locus. The highest p value for combined families was 0.0885 at the Chr1q21-23 locus. Conclusion: There is no evidence of significant linkage among 29 familial migraine families to any of the three FHM loci or to the ChrX28 region.