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
Abstract
:1. Introduction
2. Results
2.1. Distribution of mRNA NIPBL Isoforms A and B in Foetal and Adult Human Tissues
2.2. Quantitative mRNA Analysis of Isoforms A and B in Foetal and Adult Human Tissues
2.3. Structure Prediction of the C-Terminal Segment of the Isoforms A and B of the NIPBL Gene
2.4. Clinical Description
2.4.1. Patient 1
2.4.2. Patient 2
2.5. Genetic Diagnosis and Pyrosequencing Analysis in Different Tissues
2.6. DNA Damage Sensibility in Patients’ Fibroblasts
2.7. Quantification of mRNA NIPBL Isoforms A and B in Patients’ Fibroblasts
3. Discussion
4. Materials and Methods
4.1. Identification of NIPBL Isoforms A and B in Foetal and Adult Human Tissues
4.2. Quantification of mRNA NIPBL Isoforms A and B by qPCR in Human Tissues
4.3. Patients
4.4. Genetic Diagnosis and Pyrosequencing Analysis
4.5. Structural In Silico Modeling of C-Terminal Domain of NIPBL Isoforms A and B and Bioinformatic Analysis of the Missense Pathological Variant in Isoform A
4.6. Cell Culture and Colony Formation Assay
4.7. Quantification of mRNA from NIPBL Isoforms A and B in Patients’ Fibroblasts
Supplementary Materials
Acknowledgments
Author Contributions
Conflicts of Interest
References
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Clinical Data | Patient 1 | Patient 2 | |
---|---|---|---|
Anthropometric data (newborn) | Gestational age | 36 weeks | 35 weeks |
Birth weight (g) | 2600 (P10–25) | 2420 (P50) | |
Birth length (cm) | 46 (P10–25) | 46.7 (P50) | |
Birth OFC (cm) | 31 (P10–25) | 30.5 (P10–25) | |
Intrauterine growth retardation | No | No | |
Anthropometric data (last evaluation) | Age at evaluation | 14 years 3 month | 10 years 8 month |
Weight (kg) | 54 (P25–50) | 36.3 (P25–50) | |
Length (cm) | 159.5 (P25–50) | 136.5 (P3–25) | |
OFC (cm) | 52.5 (P3–25) | 52.5 (P25–50) | |
Postnatal growth retardation | No | No | |
Limb abnomalities | Bilateral brachydactyly—clinodactyly 5th finger Bilateral 2–3 syndactyly (feet) | 2–3 partial syndactyly (feet) | |
Developmental delay | + | + | |
Intellectual disability | + | + | |
Microcephaly | + | - | |
Behavior problems | + | + | |
Atypical wide nose with broad nasal bridge | + | + | |
Hypoacusia | − | - | |
Gastroesophageal reflux disease | − | + | |
Feeding (swallowing) problems | − | + | |
Hirsutism | + | - | |
Cutis marmorata | − | - |
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Puisac, B.; Teresa-Rodrigo, M.-E.; Hernández-Marcos, M.; Baquero-Montoya, C.; Gil-Rodríguez, M.-C.; Visnes, T.; Bot, C.; Gómez-Puertas, P.; Kaiser, F.J.; Ramos, F.J.; et al. 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. Int. J. Mol. Sci. 2017, 18, 481. https://doi.org/10.3390/ijms18030481
Puisac B, Teresa-Rodrigo M-E, Hernández-Marcos M, Baquero-Montoya C, Gil-Rodríguez M-C, Visnes T, Bot C, Gómez-Puertas P, Kaiser FJ, Ramos FJ, et al. 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. International Journal of Molecular Sciences. 2017; 18(3):481. https://doi.org/10.3390/ijms18030481
Chicago/Turabian StylePuisac, Beatriz, María-Esperanza Teresa-Rodrigo, María Hernández-Marcos, Carolina Baquero-Montoya, María-Concepción Gil-Rodríguez, Torkild Visnes, Christopher Bot, Paulino Gómez-Puertas, Frank J. Kaiser, Feliciano J. Ramos, and et al. 2017. "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" International Journal of Molecular Sciences 18, no. 3: 481. https://doi.org/10.3390/ijms18030481