Identification of a Novel Locus for Febrile Seizures and Epilepsy on Chromosome 21q22

Purpose: To report results of linkage analysis in a large family with autosomal dominant (AD) febrile seizures (FS) and epilepsy. Background:AD FS and epilepsy is clinically and genetically a heterogeneous group of epilepsies, frequently inherited. The most notable, generalized epilepsy with febrile...

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Bibliographic Details
Published in:Epilepsia (Copenhagen) 2006-10, Vol.47 (10), p.1622-1628
Main Authors: Hedera, Peter, Ma, Shaochun, Blair, Marcia A., Taylor, Kelly A., Hamati, Aline, Bradford, Yuki, Abou‐Khalil, Bassel, Haines, Jonathan L.
Format: Article
Language:English
Subjects:
Adult
Aged
Aged, 80 and over
Anticonvulsants. Antiepileptics. Antiparkinson agents
Biological and medical sciences
Child, Preschool
Chromosome 21
Chromosome Mapping - statistics & numerical data
Chromosomes, Human, Pair 21 - genetics
Diseases of the nervous system
Epilepsy
Epilepsy - epidemiology
Epilepsy - genetics
Family Health
Female
Generalized epilepsy with febrile seizures plus
Genetic Linkage
Genetic Markers
Genotype
Headache. Facial pains. Syncopes. Epilepsia. Intracranial hypertension. Brain oedema. Cerebral palsy
Humans
Linkage analysis
Lod Score
Male
Medical sciences
Middle Aged
Nervous system (semeiology, syndromes)
Neurology
Neuropharmacology
Pedigree
Penetrance
Pharmacology. Drug treatments
Radiotherapy. Instrumental treatment. Physiotherapy. Reeducation. Rehabilitation, orthophony, crenotherapy. Diet therapy and various other treatments (general aspects)
Seizures, Febrile - epidemiology
Seizures, Febrile - genetics
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Summary:Purpose: To report results of linkage analysis in a large family with autosomal dominant (AD) febrile seizures (FS) and epilepsy. Background:AD FS and epilepsy is clinically and genetically a heterogeneous group of epilepsies, frequently inherited. The most notable, generalized epilepsy with febrile seizures plus (GEFS+), is characterized by heterogeneous phenotypes including FS persisting beyond the usual age of remission or coexisting with afebrile seizures. Mutations in three subunits of sodium channel genes and one GABAA‐receptor subunit gene have been identified in some GEFS+ pedigrees. Six genetic loci for FS have been reported so far, but the molecular basis of FS remains unknown. Methods: We identified a five‐generation family with 13 individuals affected by FS. Evidence was found for coexisting afebrile seizures in some affected individuals. Evaluation included a detailed history and neurologic examination, as well as collection of DNA. After excluding previously identified loci associated with FS and epilepsy, a genome‐wide search was performed. Results: Two affected individuals reported only a single FS, whereas the other affected individuals had a history of repeated FS. Coexisting afebrile seizures developed in three individuals. The mode of inheritance was consistent with AD inheritance with an incomplete penetrance. Tight linkage to a group of markers on chromosome 21q22 was identified with flanking markers D21S1909 and D21S1444, and maximum 2‐point lod score 3.35 for markers D21S1910 and D21S1894. We excluded four ion‐channel genes within this 6.5‐cM locus as a cause of FS and epilepsy in this family. Conclusions: We report a novel locus on chromosome 21q22 for AD FS. Identification of the gene causing epilepsy on chromosome 21q22 will advance our understanding of inherited epilepsy and FS, and possibly other types of epilepsies.
ISSN:0013-9580
1528-1167
DOI:10.1111/j.1528-1167.2006.00637.x