Functional characterization of NIPBL physiological splice variants and eight splicing mutations in patients with cornelia de lange syndrome
Resumen: Cornelia de Lange syndrome (CdLS) is a congenital developmental disorder characterized by distinctive craniofacial features, growth retardation, cognitive impairment, limb defects, hirsutism, and multisystem involvement. Mutations in five genes encoding structural components (SMC1A, SMC3, RAD21) or functionally associated factors (NIPBL, HDAC8) of the cohesin complex have been found in patients with CdLS. In about 60% of the patients, mutations in NIPBL could be identified. Interestingly, 17% of them are predicted to change normal splicing, however, detailed molecular investigations are often missing. Here, we report the first systematic study of the physiological splicing of the NIPBL gene, that would reveal the identification of four new splicing isoforms ¿E10, ¿E12, ¿E33,34, and B’. Furthermore, we have investigated nine mutations affecting splice-sites in the NIPBL gene identified in twelve CdLS patients. All mutations have been examined on the DNA and RNA level, as well as by in silico analyses. Although patients with mutations affecting NIPBL splicing show a broad clinical variability, the more severe phenotypes seem to be associated with aberrant transcripts resulting in a shift of the reading frame.
Idioma: Inglés
DOI: 10.3390/ijms150610350
Año: 2014
Publicado en: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES 15, 6 (2014), 10350-10364
ISSN: 1661-6596

Factor impacto JCR: 2.862 (2014)
Categ. JCR: CHEMISTRY, MULTIDISCIPLINARY rank: 45 / 154 = 0.292 (2014) - Q2 - T1
Categ. JCR: BIOCHEMISTRY & MOLECULAR BIOLOGY rank: 134 / 290 = 0.462 (2014) - Q2 - T2

Financiación: info:eu-repo/grantAgreement/ES/DGA/B20
Financiación: info:eu-repo/grantAgreement/ES/FIS/PI12-01318
Financiación: info:eu-repo/grantAgreement/ES/UZ/UZ2011-BIO-02
Tipo y forma: Article (Published version)
Área (Departamento): Fisiología (Departamento de Farmacología y Fisiología)
Área (Departamento): Pediatría (Departamento de Pediatría, Radiología y Medicina Física)

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Articles > Artículos por área > Pediatría

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