Juvenile neuronal ceroid lipofuscinosis: clinical course and genetic studies in Spanish patients
| Autor: | L. Rodriguez-Revenga, María-Socorro Pérez-Poyato, M. Mar García González, Mercé Pineda Marfa, Montserrat Milá Recansens, Ramón Velázquez Fragua, Antonio Martínez-Bermejo, Rafael Camino León, Rosario Domingo Jiménez, Victoria Cusí Sánchez, Raquel Montero Sánchez, Isidre Ferrer Abizanda |
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| Rok vydání: | 2011 |
| Předmět: |
Adult
Male medicine.medical_specialty Pathology Batten disease Adolescent DNA Mutational Analysis Young Adult Cognition Neuronal Ceroid-Lipofuscinoses Internal medicine Genotype Genetics medicine Humans Missense mutation Cognitive decline Child Genetics (clinical) Psychomotor learning business.industry Mental Disorders medicine.disease Genetics Population Phenotype Molecular Diagnostic Techniques CLN3 Spain Disease Progression Female Neuronal ceroid lipofuscinosis Age of onset business |
| Zdroj: | Journal of Inherited Metabolic Disease. 34:1083-1093 |
| ISSN: | 1573-2665 0141-8955 |
| DOI: | 10.1007/s10545-011-9323-7 |
| Popis: | Juvenile neuronal ceroid lipofuscinosis (JNCL, NCL3, Batten disease) is usually caused by a 1.02-kb deletion in the CLN3 gene. Mutations in the CLN1 gene may be associated with a variant form of JNCL (vJNCL). We report the clinical course and molecular studies in 24 patients with JNCL collected from 1975 to 2010 with the aim of assessing the natural history of the disorder and phenotype/genotype correlations. Patients were classified into the groups of vJNCL with mutations in the CLN1 gene and/or granular osmiophilic deposit (GROD) inclusion bodies (n = 11) and classic JNCL (cJNCL) with mutations in the CLN3 gene and/or fingerprint (FP) profiles (n = 13). Psychomotor impairment included regression of acquired skills, cognitive decline, and clinical manifestations of the disease. We used Kaplan-Meier analyses to estimate the age of onset of psychomotor impairment. Patients with vJNCL showed learning delay at an earlier age (median 4 years, 95% confidence interval [CI] 3.1–4.8) than those in the cJNCL group (median 8 years, 95% CI 6.2–9.7) (P = 0.001) and regression of acquired skills at a younger age. Patients with vJNCL showed a more severe and progressive clinical course than those with cJNCL. There may be a Gypsy ancestry for V181L missense mutation in the CLN1 gene. The rate of disease progression may be useful to diagnose vJNCL or cJNCL, which should be confirmed by molecular studies in CLN1/CLN3 genes. Further studies of genotype/phenotype correlation will be helpful for understanding the pathogenesis of this disease. |
| Databáze: | OpenAIRE |
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