RESUMO
Mulibrey nanism (muscle-liver-brain-eye nanism; MUL) is an autosomal recessively transmitted disease characterized by severe growth delays of prenatal onset caused by mutations in the TRIM37 gene. Recent studies on the subcellular localization revealed that the TRIM37 (KIAA0898) protein is located in peroxisomes. Therefore, MUL has been classified as a new peroxisomal disorder. Up to now, four mutations have been reported, all of which lead to frameshifts and truncated proteins. In this study, mutation screening was performed for the coding region of the TRIM37 gene in a Turkish family by means of RT-PCR and direct cDNA sequencing. We have identified a novel mutation resulting in a frameshift cosegregating within the family. Finally, we report on the presence of novel splice variants observed in lymphoblastoid cells and muscle tissue of normal subjects and patients.
Assuntos
Nanismo/genética , Mutação/genética , Proteínas Nucleares , Transtornos Peroxissômicos/genética , Proteínas/genética , Sítios de Splice de RNA/genética , Sequência de Bases , Análise Mutacional de DNA , Nanismo/fisiopatologia , Feminino , Mutação da Fase de Leitura/genética , Humanos , Masculino , Dados de Sequência Molecular , Músculos/metabolismo , Linhagem , Transtornos Peroxissômicos/fisiopatologia , Fenótipo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Proteínas com Motivo Tripartido , Turquia , Ubiquitina-Proteína LigasesRESUMO
Chorea Huntington (CH) is a dominantly inherited, neurodegenerative disease usually with adult onset. The course of CH is characterized by movement disturbances, psychiatric symptoms and it may lead to dementia. Typically death occurs after 10 to 20 years of CH duration. Invariably, the underlying mutation concerns an expansion of a polymorphic (CAG) n stretch in the huntingtin gene. Statistically, larger expansions lead to earlier onset of the disease. We report on a girl with a huntingtin allele of > 140 (CAG) n repeats. Unspecific neurological symptoms were noted at the age of 4.3 years followed by rapid disease progression with psychomotor deterioration.