RESUMO
BACKGROUND: Familial glucose transporter type 1 (GLUT1) deficiency due to autosomal dominant inheritance of SLC2A1 mutations is associated with paroxysmal exertional dyskinesia; epilepsy and intellectual disability occur in some family members. We recently demonstrated that GLUT1 deficiency occurs in over 10% of patients with early-onset absence epilepsy. METHODS: This family study analyses the phenotypes in 2 kindreds segregating SLC2A1 mutations identified through probands with early-onset absence epilepsy. One comprised 9 individuals with mutations over 3 generations; the other had 6 individuals over 2 generations. RESULTS: Of 15 subjects with SLC2A1 mutations, epilepsy occurred in 12. Absence seizures were the most prevalent seizure type (10/12), with onset from 3 to 34 years of age. Epilepsy phenotypes varied widely, including idiopathic generalized epilepsies (IGE) with absence (8/12), myoclonic-astatic epilepsy (2/12), and focal epilepsy (2/12). Paroxysmal exertional dyskinesia occurred in 7, and was subtle and universally undiagnosed prior to molecular diagnosis. There were 2 unaffected mutation carriers. CONCLUSIONS: GLUT1 deficiency is an important monogenic cause of absence epilepsies with onset from early childhood to adult life. Individual cases may be phenotypically indistinguishable from common forms of IGE. Although subtle paroxysmal exertional dyskinesia is a helpful diagnostic clue, it is far from universal. The phenotypic spectrum of GLUT1 deficiency is considerably greater than previously recognized. Diagnosis of GLUT1 deficiency has important treatment and genetic counseling implications.
Assuntos
Epilepsia Tipo Ausência/genética , Transportador de Glucose Tipo 1/deficiência , Transportador de Glucose Tipo 1/genética , Mutação , Fenótipo , Adolescente , Adulto , Idade de Início , Criança , Pré-Escolar , Coreia/líquido cefalorraquidiano , Coreia/diagnóstico , Coreia/genética , Epilepsia Tipo Ausência/líquido cefalorraquidiano , Epilepsia Tipo Ausência/diagnóstico , Família , Glucose/líquido cefalorraquidiano , Humanos , Linhagem , Adulto JovemRESUMO
Genome-wide association studies are utilized for gene discovery in common diseases. Genotypes of large groups of unrelated patients are compared to controls. This has become feasible due to the recent technical advances in genomics and convincing positive results are now regularly being published. This review is an accessible introduction to the genetic and technical knowledge needed to interpret such studies. Genome-wide association studies are being applied to many neurologic diseases. Here we use idiopathic generalized epilepsy as an example to highlight the phenotyping, sample size, and statistical issues that must be addressed in such studies. These studies are likely to transform our understanding of complex neurologic diseases in the next few years.
Assuntos
Mapeamento Cromossômico/métodos , Ensaios Clínicos como Assunto , Estudo de Associação Genômica Ampla/métodos , Doenças do Sistema Nervoso/epidemiologia , Doenças do Sistema Nervoso/genética , Polimorfismo de Nucleotídeo Único/genética , Predisposição Genética para Doença/epidemiologia , Predisposição Genética para Doença/genética , HumanosRESUMO
Approximately 2,200 laboratories participated in the 1978 Comprehensive Blood Bank Survey of the College of American Pathologists. Correct responses of the test results on the blood specimens were determined by 13 Referee Laboratories. Participants' results were compared with Reference Laboratory results. Overall performance on ABO and Rh D typing revealed 98.3% concurrence. Errors in ABO grouping and Rh typing were most frequently found to be "clerical" rather than "technical." Antibody studies and crossmatching revealed variable results in the detection, identification, and evaluation of the clinical significance of a weak, naturally occurring antibody (anti-P1) and in the crossmatching of weak immune antibodies (anti-e and anti-D). Over 95% of participants correctly responded on antibody studies and crossmatching results with a serum containing a moderately strong anti-Fya. Ungraded specimens provided during the year yielded "state of the art" information on a variety of problems.