title: The genetics of reading disability in an often excluded sample: novel loci suggested for reading disability in Rolandic epilepsy.
abstract: BACKGROUND
  Reading disability (RD) is a common neurodevelopmental disorder with genetic basis established in families segregating "pure" dyslexia. RD commonly occurs in neurodevelopmental disorders including Rolandic Epilepsy (RE), a complex genetic disorder. We performed genomewide linkage analysis of RD in RE families, testing the hypotheses that RD in RE families is genetically heterogenenous to pure dyslexia, and shares genetic influences with other sub-phenotypes of RE.
  
  
  METHODS
  We initially performed genome-wide linkage analysis using 1000 STR markers in 38 US families ascertained through a RE proband; most of these families were multiplex for RD. We analyzed the data by two-point and multipoint parametric LOD score methods. We then confirmed the linkage evidence in a second US dataset of 20 RE families. We also resequenced the SEMA3C gene at the 7q21 linkage locus in members of one multiplex RE/RD pedigree and the DISC1 gene in affected pedigrees at the 1q42 locus.
  
  
  RESULTS
  In the discovery dataset there was suggestive evidence of linkage for RD to chromosome 7q21 (two-point LOD score 3.05, multipoint LOD 3.08) and at 1q42 (two-point LOD 2.87, multipoint LOD 3.03). Much of the linkage evidence at 7q21 derived from families of French-Canadian origin, whereas the linkage evidence at 1q42 was well distributed across all the families. There was little evidence for linkage at known dyslexia loci. Combining the discovery and confirmation datasets increased the evidence at 1q42 (two-point LOD = 3.49, multipoint HLOD = 4.70), but decreased evidence at 7q21 (two-point LOD = 2.28, multipoint HLOD  = 1.81), possibly because the replication sample did not have French Canadian representation.
  
  
  CONCLUSIONS
  Reading disability in rolandic epilepsy has a genetic basis and may be influenced by loci at 1q42 and, in some populations, at 7q21; there is little evidence of a role for known DYX loci discovered in "pure" dyslexia pedigrees. 1q42 and 7q21 are candidate novel dyslexia loci.
authors: Child Health Evaluative Sciences, The Hospital for Sick Children, Toronto, Canada.
authors: Lisa J
authors: LJ
authors: Strug
authors: Laura
authors: L
authors: Addis
authors: Theodore
authors: T
authors: Chiang
authors: Zeynep
authors: Z
authors: Baskurt
authors: Weili
authors: W
authors: Li
authors: Tara
authors: T
authors: Clarke
authors: Huntley
authors: H
authors: Hardison
authors: Steven L
authors: SL
authors: Kugler
authors: David E
authors: DE
authors: Mandelbaum
authors: Edward J
authors: EJ
authors: Novotny
authors: Steven M
authors: SM
authors: Wolf
authors: Deb K
authors: DK
authors: Pal
mesh_terms: D002170:Canada; D002878:Chromosomes, Human, Pair 1 / Q000235:genetics; D002897:Chromosomes, Human, Pair 7 / Q000235:genetics; D030541:Databases, Genetic; D004410:Dyslexia / Q000150:complications* / Q000235:genetics*; D019305:Epilepsy, Rolandic / Q000150:complications* / Q000235:genetics*; D005260:Female; D056426:Genetic Loci / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D015894:Genome, Human / Q000235:genetics; D006801:Humans; D007806:Language Disorders / Q000150:complications / Q000235:genetics; D008126:Lod Score; D008297:Male; D009419:Nerve Tissue Proteins / Q000235:genetics; D010375:Pedigree; D015203:Reproducibility of Results; D039961:Semaphorins / Q000235:genetics; D017422:Sequence Analysis, DNA; D066229:Speech Sound Disorder
chemical_list: C412476:DISC1 protein, human; D009419:Nerve Tissue Proteins; C543908:Sema3C protein, human; D039961:Semaphorins