Linkage Analysis of Idiopathic Generalized Epilepsy (IGE) and Marker Loci on Chromosome 6p in Families of Patients with Juvenile Myoclonic Epilepsy: No Evidence for an Epilepsy Locus in the HLA Region

Overview

Journal Am J Hum Genet

Publisher Cell Press

Specialty Genetics

Date 1993 Sep 1

PMID 8352275

Citations 13

Authors

W P Whitehouse

M Rees

D Curtis

A Sundqvist

K Parker

E Chung

D Baralle

R M Gardiner

Affiliations

Soon will be listed here.

Abstract

Evidence for a locus (EJM1) in the HLA region of chromosome 6p predisposing to idiopathic generalized epilepsy (IGE) in the families of patients with juvenile myoclonic epilepsy (JME) has been obtained in two previous studies of separately ascertained groups of kindreds. Linkage analysis has been undertaken in a third set of 25 families including a patient with JME and at least one first-degree relative with IGE. Family members were typed for eight polymorphic loci on chromosome 6p: F13A, D6S89, D6S109, D6S105, D6S10, C4B, DQA1/A2, and TCTE1. Pairwise and multipoint linkage analysis was carried out assuming autosomal dominant and autosomal recessive inheritance and age-dependent high or low penetrance. No significant evidence in favor of linkage was obtained at any locus. Multipoint linkage analysis generated significant exclusion data (lod score < -2.0) at HLA and for a region 10-30 cM telomeric to HLA, the extent of which varied with the level of penetrance assumed. These observations indicate that genetic heterogeneity exists within this epilepsy phenotype.

Citing Articles

BRD2 (RING3) is a probable major susceptibility gene for common juvenile myoclonic epilepsy.

Pal D, Evgrafov O, Tabares P, Zhang F, Durner M, Greenberg D Am J Hum Genet. 2003; 73(2):261-70.

PMID: 12830434 PMC: 1180366. DOI: 10.1086/377006.

Reproducibility and complications in gene searches: linkage on chromosome 6, heterogeneity, association, and maternal inheritance in juvenile myoclonic epilepsy.

Greenberg D, Durner M, Keddache M, Shinnar S, Resor S, Moshe S Am J Hum Genet. 2000; 66(2):508-16.

PMID: 10677311 PMC: 1288104. DOI: 10.1086/302763.

Evidence for linkage of adolescent-onset idiopathic generalized epilepsies to chromosome 8-and genetic heterogeneity.

Durner M, Zhou G, Fu D, Abreu P, Shinnar S, Resor S Am J Hum Genet. 1999; 64(5):1411-9.

PMID: 10205274 PMC: 1377879. DOI: 10.1086/302371.

Childhood absence epilepsy with tonic-clonic seizures and electroencephalogram 3-4-Hz spike and multispike-slow wave complexes: linkage to chromosome 8q24.

Fong G, Shah P, Gee M, Serratosa J, Castroviejo I, Khan S Am J Hum Genet. 1998; 63(4):1117-29.

PMID: 9758624 PMC: 1377498. DOI: 10.1086/302066.

Familial infantile convulsions and paroxysmal choreoathetosis: a new neurological syndrome linked to the pericentromeric region of human chromosome 16.

Szepetowski P, Rochette J, Berquin P, Piussan C, Lathrop G, Monaco A Am J Hum Genet. 1997; 61(4):889-98.

PMID: 9382100 PMC: 1715981. DOI: 10.1086/514877.

References

Lathrop G, Lalouel J, Julier C, Ott J . Multilocus linkage analysis in humans: detection of linkage and estimation of recombination. Am J Hum Genet. 1985; 37(3):482-98. PMC: 1684598. View

Feinberg A, Vogelstein B . A technique for radiolabeling DNA restriction endonuclease fragments to high specific activity. Anal Biochem. 1983; 132(1):6-13. DOI: 10.1016/0003-2697(83)90418-9. View

Zoghbi H, Daiger S, McCall A, OBrien W, Beaudet A . Extensive DNA polymorphism at the factor XIIIa (F13A) locus and linkage to HLA. Am J Hum Genet. 1988; 42(6):877-83. PMC: 1715200. View

Weber J, May P . Abundant class of human DNA polymorphisms which can be typed using the polymerase chain reaction. Am J Hum Genet. 1989; 44(3):388-96. PMC: 1715443. View

Greenberg D, Delgado-Escueta A, Widelitz H, Sparkes R, Treiman L, Maldonado H . Juvenile myoclonic epilepsy (JME) may be linked to the BF and HLA loci on human chromosome 6. Am J Med Genet. 1988; 31(1):185-92. DOI: 10.1002/ajmg.1320310125. View

Panayiotopoulos C, Obeid T . Juvenile myoclonic epilepsy: an autosomal recessive disease. Ann Neurol. 1989; 25(5):440-3. DOI: 10.1002/ana.410250504. View

Ott J, Bhattacharya S, Chen J, Denton M, Donald J, Dubay C . Localizing multiple X chromosome-linked retinitis pigmentosa loci using multilocus homogeneity tests. Proc Natl Acad Sci U S A. 1990; 87(2):701-4. PMC: 53333. DOI: 10.1073/pnas.87.2.701. View

Ott J . Cutting a Gordian knot in the linkage analysis of complex human traits. Am J Hum Genet. 1990; 46(2):219-21. PMC: 1684983. View

Greenberg D . Inferring mode of inheritance by comparison of lod scores. Am J Med Genet. 1989; 34(4):480-6. DOI: 10.1002/ajmg.1320340406. View

10.

Elston R . Man bites dog? The validity of maximizing lod scores to determine mode of inheritance. Am J Med Genet. 1989; 34(4):487-8. DOI: 10.1002/ajmg.1320340407. View

11.

Risch N . Genetic linkage and complex diseases, with special reference to psychiatric disorders. Genet Epidemiol. 1990; 7(1):3-16; discussion 17-45. DOI: 10.1002/gepi.1370070103. View

12.

Campbell R, Dunham I, Kendall E, Sargent C . Polymorphism of the human complement component C4. Exp Clin Immunogenet. 1990; 7(1):69-84. View

13.

Litt M, Luty J . Dinucleotide repeat polymorphism at the D6S89 locus. Nucleic Acids Res. 1990; 18(14):4301. PMC: 331240. DOI: 10.1093/nar/18.14.4301. View

14.

Bidwell J, Bidwell E, Bradley B . HLA class II genes: typing by DNA analysis. Baillieres Clin Haematol. 1990; 3(2):355-84. DOI: 10.1016/s0950-3536(05)80055-1. View

15.

Delgado-Escueta A, Greenberg D, Weissbecker K, Liu A, Treiman L, Sparkes R . Gene mapping in the idiopathic generalized epilepsies: juvenile myoclonic epilepsy, childhood absence epilepsy, epilepsy with grand mal seizures, and early childhood myoclonic epilepsy. Epilepsia. 1990; 31 Suppl 3:S19-29. DOI: 10.1111/j.1528-1157.1990.tb05855.x. View

16.

Weeks D, Lehner T, Squires-Wheeler E, Kaufmann C, Ott J . Measuring the inflation of the lod score due to its maximization over model parameter values in human linkage analysis. Genet Epidemiol. 1990; 7(4):237-43. DOI: 10.1002/gepi.1370070402. View

17.

Clerget-Darpoux F, Babron M, Bonaiti-Pellie C . Assessing the effect of multiple linkage tests in complex diseases. Genet Epidemiol. 1990; 7(4):245-53. DOI: 10.1002/gepi.1370070403. View

18.

Weissbecker K, Durner M, Janz D, Scaramelli A, Sparkes R, Spence M . Confirmation of linkage between juvenile myoclonic epilepsy locus and the HLA region of chromosome 6. Am J Med Genet. 1991; 38(1):32-6. DOI: 10.1002/ajmg.1320380109. View

19.

Weber J, Kwitek A, May P, Zoghbi H . Dinucleotide repeat polymorphism at the D6S105 locus. Nucleic Acids Res. 1991; 19(4):968. PMC: 333759. DOI: 10.1093/nar/19.4.968. View

20.

Ranum L, Chung M, Duvick L, Zoghbi H, Orr H . Dinucleotide repeat polymorphism at the D6S109 locus. Nucleic Acids Res. 1991; 19(5):1171. PMC: 333832. DOI: 10.1093/nar/19.5.1171-a. View