RESUMO
BACKGROUND: Juvenile myoclonic epilepsy (JME) accounts for 3 to 12% of all epilepsies. In 2004, the GENESS Consortium demonstrated four missense mutations in Myoclonin1/EFHC1 of chromosome 6p12.1 segregating in 20% of Hispanic families with JME. OBJECTIVE: To examine what percentage of consecutive JME clinic cases have mutations in Myoclonin1/EFHC1. METHODS: We screened 44 consecutive patients from Mexico and Honduras and 67 patients from Japan using heteroduplex analysis and direct sequencing. RESULTS: We found five novel mutations in transcripts A and B of Myoclonin1/EFHC1. Two novel heterozygous missense mutations (c.755C>A and c.1523C>G) in transcript A occurred in both a singleton from Mexico and another singleton from Japan. A deletion/frameshift (C.789del.AV264fsx280) in transcript B was present in a mother and daughter from Mexico. A nonsense mutation (c.829C>T) in transcript B segregated in four clinically and seven epileptiform-EEG affected members of a large Honduran family. The same nonsense mutation (c.829C>T) occurred as a de novo mutation in a sporadic case. Finally, we found a three-base deletion (-364--362del.GAT) in the promoter region in a family from Japan. CONCLUSION: Nine percent of consecutive juvenile myoclonic epilepsy cases from Mexico and Honduras clinics and 3% of clinic patients from Japan carry mutations in Myoclonin1/EFCH1. These results represent the highest number and percentage of mutations found for a juvenile myoclonic epilepsy causing gene of any population group.
Assuntos
Proteínas de Ligação ao Cálcio/genética , Saúde da Família , Mutação , Epilepsia Mioclônica Juvenil/genética , Canais de Cloro CLC-2 , Canais de Cloreto/genética , Análise Mutacional de DNA/métodos , Feminino , Genótipo , Honduras/epidemiologia , Humanos , Japão , Masculino , México/epidemiologia , Epilepsia Mioclônica Juvenil/epidemiologia , Fenótipo , Regiões Promotoras Genéticas , Receptores de GABA-A/genéticaRESUMO
We describe 2 patients with adult-onset type II citrullinemia who developed transient hypoproteinemia and jaundice in early infancy. Liver histology showed a marked fatty change and fibrosis. After the patients had lived without symptoms to the ages of 5 and 16 years, respectively, the diagnosis was made by genetic analysis.
Assuntos
Citrulinemia/diagnóstico , Adolescente , Biópsia , Pré-Escolar , Citrulinemia/genética , Citrulinemia/patologia , Fígado Gorduroso/patologia , Feminino , Genótipo , Humanos , Fígado/patologia , Masculino , Mutação Puntual , Reação em Cadeia da PolimeraseRESUMO
BACKGROUND: A mysterious disease spread over Cuba from 1991 to 1993, the cause of which has not been fully established. Major symptoms were the same in patients with the Cuban disease as in patients with subacute myelo-optico-neuropathy (SMON), which had occurred in Japan nearly 30 years ago and from which Inoue-Melnick virus (IMV) type 1 was first isolated. We investigated the presence of IMV in cerebrospinal fluid samples of patients with this epidemic neuropathy in Cuba. METHODS: The established method for detecting IMV in MRC-5 fibroblasts was used throughout the study, which was conducted in two independent laboratories, one in Buffalo, NY, and the other in Kyoto, Japan. The cerebrospinal fluid samples of 20 patients and four controls were provided by Cuban researchers. RESULTS: All cerebrospinal fluid specimens from 20 Cuban patients tested were positive for IMV type 2 (100%), and four cerebrospinal fluid specimens from Cuban controls were negative for IMV (0%). These clear-cut results were identical in both laboratories. CONCLUSION: Our study indicates an important association of IMV type 2 with patients of this Cuban epidemic. The etiologic role of IMV type 2 in the epidemic neuropathy in Cuba, along with weak cytopathic effect viruses isolated by the Cuban group, remains to be elucidated.
Assuntos
Herpesviridae/isolamento & purificação , Mielite/líquido cefalorraquidiano , Neurite Óptica/líquido cefalorraquidiano , Animais , Anticorpos Antivirais/análise , Linhagem Celular , Líquido Cefalorraquidiano/virologia , Cuba/epidemiologia , Surtos de Doenças , Fibroblastos , Herpesviridae/imunologia , Humanos , Mielite/epidemiologia , Mielite/virologia , Testes de Neutralização , Neurite Óptica/epidemiologia , Neurite Óptica/virologia , Prevalência , Coelhos , SíndromeRESUMO
A male infant with typical clinical and biochemical findings of Zellweger syndrome, but in whom hepatic peroxisomes were detected by electron microscopy, had profound hypotonia, hepatomegaly, typical facial appearance including large fontanelle and frontal bossing, convulsions, panaminoaciduria, and hyperammonemia. He died of liver failure at age 5 months. There were increased levels of very long chain fatty acids and trihydroxycoprostanic acid in serum, and increased excretion of dicarboxylic acids and tyrosine metabolites in the urine. Levels of peroxisomal enzymes, acyl coenzyme A oxidase, bifunctional protein, 3-ketoacyl coenzyme A thiolase, and dihydroxyacetone phosphate acyltransferase in the liver tissue from the patient were all deficient, findings consistent with Zellweger syndrome. However, immunocytochemical study and electron microscopic examination of the liver at autopsy revealed that hepatic peroxisomes were present at a level similar to that in a control subject. These observations suggest further heterogeneity in Zellweger syndrome and a different pathogenesis in this variant case.