Clinical score of 62 Italian patients with Cornelia de Lange syndrome and correlations with the presence and type of NIPBL mutation
| Autor: | Florinda Cavalleri, Angelo Selicorni, Angela Bentivegna, Lidia Larizza, Luigi Memo, Maria Teresa Divizia, Cinzia Sforzini, Maura Masciadri, Silvia Russo, Gioacchino Scarano, Paola Castronovo, E. Tarantino, Donatella Milani, Cristina Gervasini, A. Domi |
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| Přispěvatelé: | Selicorni, A, Russo, S, Gervasini, C, Castronovo, P, Milani, D, Cavalleri, F, Bentivegna, A, Masciadri, M, Domi, A, Divizia, M, Sforzini, C, Tarantino, E, Memo, L, Scarano, G, Larizza, L |
| Jazyk: | angličtina |
| Rok vydání: | 2007 |
| Předmět: |
Adult
Male medicine.medical_specialty Cornelia de Lange Syndrome clinical score Cornelia de Lange syndrome genotype–phenotype correlation NIPBL mutation Adolescent MED/03 - GENETICA MEDICA DNA Mutational Analysis Cell Cycle Proteins Biology SMC1A medicine.disease_cause Cohort Studies Central nervous system disease De Lange Syndrome Internal medicine Genotype Prevalence Genetics medicine Humans Missense mutation Child Genetics (clinical) Mutation Infant Proteins NIPBL Middle Aged medicine.disease Italy Child Preschool Cohort Female |
| Popis: | Cornelia de Lange syndrome (CdLS) is a rare multisystem disorder characterized by facial dysmorphisms, upper limb abnormalities, growth and cognitive retardation. About half of all patients with CdLS carry mutations in the NIPBL gene. The first Italian CdLS cohort involving 62 patients (including 4 related members) was screened for NIPBL mutations after a clinical evaluation using a quantitative score that integrates auxological, malformation and neurodevelopmental parameters. The patients were classified as having an overall 'severe', 'moderate' or 'mild' phenotype. NIPBL screening showed 26 mutations so classified: truncating (13), splice-site (8), missense (3), in-frame deletion (1) and regulatory (1). The truncating mutations were most frequently found in the patients with a high clinical score, whereas most of the splice-site and all missense mutations clustered in the low-medium score groups. The NIPBL-negative group included patients covering the entire clinical spectrum. The prevalence of a severe phenotype in the mutated group and a mild phenotype in the non-mutated group was statistically significant. In terms of the isolated clinical signs, the statistically significant differences between the mutation-positive and mutation-negative individuals were pre- and post-natal growth deficits, limb reduction, and delayed speech development. The proposed score seems to be a valuable means of prioritizing the patients with CdLS to undergo an NIPBL mutation test. |
| Databáze: | OpenAIRE |
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