mRNA quantification of NIPBL isoforms A and B in adult and fetal human tissues, and a potentially pathological variant affecting only isoform a in two patients with Cornelia de Lange syndrome

Puisac, B. (Universidad de Zaragoza) ; Teresa-Rodrigo, M. ; Hernández-Marcos, M. ; Baquero-Montoya, C. ; Gil-Rodríguez, M.C (Universidad de Zaragoza) ; Visnes, T. ; Bot, C. ; Gómez-Puertas, P. ; Kaiser, F.J. ; Ramos, F.J. (Universidad de Zaragoza) ; Ström, L. ; Pié, J. (Universidad de Zaragoza)

Resumen: Cornelia de Lange syndrome (CdLS) is a congenital developmental disorder characterized by craniofacial dysmorphia, growth retardation, limb malformations, and intellectual disability. Approximately 60% of patients with CdLS carry a recognizable pathological variant in the NIPBL gene, of which two isoforms, A and B, have been identified, and which only differ in the C-terminal segment. In this work, we describe the distribution pattern of the isoforms A and B mRNAs in tissues of adult and fetal origin, by qPCR (quantitative polymerase chain reaction). Our results show a higher gene expression of the isoform A, even though both seem to have the same tissue distribution. Interestingly, the expression in fetal tissues is higher than that of adults, especially in brain and skeletal muscle. Curiously, the study of fibroblasts of two siblings with a mild CdLS phenotype and a pathological variant specific of the isoform A of NIPBL (c.8387A > G; P.Tyr2796Cys), showed a similar reduction in both isoforms, and a normal sensitivity to DNA damage. Overall, these results suggest that the position of the pathological variant at the 3´ end of the NIPBL gene affecting only isoform A, is likely to be the cause of the atypical mild phenotype of the two brothers.

Idioma: Inglés

DOI: 10.3390/ijms18030481

Año: 2017

Publicado en: International Journal of Molecular Sciences 18, 3 (2017), 481 [12 pp]
ISSN: 1661-6596

Factor impacto JCR: 3.687 (2017)

Categ. JCR: BIOCHEMISTRY & MOLECULAR BIOLOGY rank: 90 / 292 = 0.308 (2017) - Q2 - T1
Categ. JCR: CHEMISTRY, MULTIDISCIPLINARY rank: 52 / 169 = 0.308 (2017) - Q2 - T1

Factor impacto SCIMAGO: 1.26 - Medicine (miscellaneous) (Q1) - Physical and Theoretical Chemistry (Q1) - Computer Science Applications (Q1) - Inorganic Chemistry (Q1) - Spectroscopy (Q1) - Organic Chemistry (Q1) - Molecular Biology (Q2) - Catalysis (Q2)

Financiación: info:eu-repo/grantAgreement/ES/DGA/B20
Financiación: info:eu-repo/grantAgreement/ES/FIS/PI15-00707
Financiación: info:eu-repo/grantAgreement/ES/MICINN/IPT2011-0964-900000
Financiación: info:eu-repo/grantAgreement/ES/MICINN/SAF2011-13156-E

Tipo y forma: Artículo (Versión definitiva)

Área (Departamento): Área Fisiología (Dpto. Farmacología y Fisiolog.)
Área (Departamento): Área Pediatría (Dpto. Pediatría Radiol.Med.Fís)