RESUMEN
Interstitial deletions of chromosome 3 are rare, and only one patient with a microdeletion of 3p21.31 has been reported to date. We identified two additional cases of patients with microdeletions of 3p21.31. The characteristic clinical features of developmental delay and distinctive facial features (including arched eyebrows, hypertelorism, epicanthus, and micrognathia) were seen both in the previously reported patient and in the two newly identified patients. In these two new cases, additional features, including elevated serum creatine kinase levels and characteristic neuroradiological features with white matter involvement, were seen. These features had not been described in the previous case in which the patient was examined during infancy, suggesting an age-dependent mechanism. The shortest region of overlap among the three deletions narrowed down the candidate genes that may be responsible for the common neurological features to the bassoon (presynaptic cytomatrix protein) gene (BSN), which has an important function in neuronal synapses. In this study, we confirmed common phenotypic features in the patients with microdeletions of 3p21.31 and identified additional features that have not been reported previously. Because the constellation of such characteristic features is quite unique, clinical manifestations of the patients with microdeletions of 3p21.31 would be clinically recognizable as a contiguous gene deletion syndrome.
Asunto(s)
Deleción Cromosómica , Cromosomas Humanos Par 3/genética , Discapacidades del Desarrollo/fisiopatología , Leucoencefalopatías/fisiopatología , Anomalías Múltiples/sangre , Anomalías Múltiples/genética , Anomalías Múltiples/fisiopatología , Adolescente , Preescolar , Creatina Quinasa/sangre , Discapacidades del Desarrollo/sangre , Femenino , Humanos , Leucoencefalopatías/sangre , Leucoencefalopatías/complicaciones , Proteínas del Tejido Nervioso/sangre , FenotipoAsunto(s)
Calcinosis/diagnóstico , Errores Innatos del Metabolismo de los Carbohidratos/diagnóstico , Catarata/diagnóstico , Hemólisis , Proteínas de Transporte de Monosacáridos/deficiencia , Potasio/sangre , Encéfalo/diagnóstico por imagen , Encéfalo/fisiopatología , Calcinosis/dietoterapia , Calcinosis/genética , Calcinosis/fisiopatología , Errores Innatos del Metabolismo de los Carbohidratos/dietoterapia , Errores Innatos del Metabolismo de los Carbohidratos/genética , Errores Innatos del Metabolismo de los Carbohidratos/fisiopatología , Catarata/dietoterapia , Catarata/genética , Catarata/fisiopatología , Diagnóstico Diferencial , Dieta Cetogénica , Femenino , Transportador de Glucosa de Tipo 1/genética , Humanos , Lactante , Proteínas de Transporte de Monosacáridos/genéticaRESUMEN
INTRODUCTION: Galactosialidosis is a rare lysosomal storage disease caused by a combined deficiency of GM1 ß-galactosidase (ß-gal) and neuraminidase secondary to a defect of a lysosomal enzyme protective protein/cathepsin A (PPCA) and mutation in CTSA gene. Three subtypes are recognized: early infantile, late infantile, and juvenile/adult. There is no specific therapy for patients with galactosialidosis at this time. OBJECTIVES: The aim of this study was to determine the chaperone effect of N-octyl-4-epi-ß-valienamine (NOEV) on ß-gal proteins in skin fibroblasts of PPCA-deficit patients. METHODS: ß-Gal and neuraminidase activities were measured for the diagnosis of the patients with galactosialidosis. Western blotting for PPCA protein and direct sequencing for CTSA gene were performed. Cultured skin fibroblast were treated with NOEV. RESULTS: We report four novel patients with galactosialidosis: one had the early infantile form and the other three had the juvenile/adult form. We found that NOEV stabilized ß-gal activity in lysate from cultured skin fibroblasts from these patients. Treatment with NOEV significantly enhanced ß-gal activity in cultured skin fibroblasts in the absence of PPCA. CONCLUSIONS: Our results indicate the possibility that NOEV chaperone therapy might have a beneficial effect, at least in part, for patients with galactosialidosis.