RESUMO
The neuronal ceroid lipofuscinoses (NCLs) form a group of autosomal recessively inherited neurodegenerative disorders that mainly affect children. Ten NCL forms can be distinguished by age at onset, clinicopathologic features, and genetics. In eight of these forms, the underlying genes have been identified. At present, approximately 10% of all patients do not fall into one of the eight known genetic forms of NCL. We have identified two Asian families with two novel homozygous mutations in the CLN5 gene. In the first Pakistani family, two children developed symptoms of an early juvenile NCL. After exclusion of mutations in genes known to be associated with this age of onset in families from many different countries (CLN1, CLN2, CLN3, CLN6, CLN8 and CLN10) SNP array-based homozygosity mapping led to the identification of a novel homozygous mutation c.1072_1073delTT (p.Leu358AlafsX4) in CLN5. In the second Afghan family, two children developed symptoms of a late infantile NCL. The mutation c.1137G>T (p.Trp379Cys) in CLN5 was identified. The affected children in these families represent the first reported CLN5 patients originating in Asian sibships. Expression analysis showed that mutant p.Leu358AlafsX4 CLN5 is truncated and lacks a used N-glycosylation site at Asn401. The missense mutation p.Trp379Cys affected neither the size nor glycosylation of the CLN5 protein. Double immunofluorescence microscopy showed that while the wild-type CLN5 protein is localized in lysosomes, both mutant CLN5 proteins are retained in the endoplasmic reticulum rather than reaching the lysosome.
Assuntos
Povo Asiático , Retículo Endoplasmático/metabolismo , Proteínas de Membrana/metabolismo , Lipofuscinoses Ceroides Neuronais/metabolismo , Proteínas/metabolismo , Irmãos , Adolescente , Animais , Povo Asiático/genética , Linhagem Celular , Criança , Pré-Escolar , DNA Complementar/genética , Evolução Fatal , Feminino , Humanos , Espaço Intracelular/metabolismo , Proteínas de Membrana Lisossomal , Masculino , Proteínas Mutantes/metabolismo , Mutação/genética , Lipofuscinoses Ceroides Neuronais/genética , Paquistão , Transporte Proteico , Tripeptidil-Peptidase 1RESUMO
The central nervous system is involved in 10-20% of cases in Lyme disease. The neurological symptoms, time course of the disease and imaging findings are multifaceted. We report two patients with cervical radiculitis. Magnetic resonance imaging revealed strong enhancement of the cervical nerve roots on contrast-enhanced T1-weighted images. These imaging patterns of borrelia-associated radiculitis have not been reported before. Knowledge of these imaging features may help to diagnose neuroborreliosis, which presents with non-specific symptoms.
