Molecular characterization of two novel intronic variants of NIPBL gene detected in unrelated Cornelia de Lange syndrome patients
Abstract Background Cornelia de Lange syndrome (CdLS), a rare, multisystemic disorder, has been linked to genetic alterations in NIPBL, SMC1A, SMC3, HDAC8, and RAD21 genes. Approximately 60% of CdLS patients harbor various NIPBL variants. Genetic changes predicted to affect NIPBL gene splicing repre...
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| Format: | Article |
| Language: | English |
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BMC
2019-01-01
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| Series: | BMC Medical Genetics |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s12881-018-0738-y |
| _version_ | 1818408287215812608 |
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| author | Natalia Krawczynska Jolanta Wierzba Jacek Jasiecki Bartosz Wasag |
| author_facet | Natalia Krawczynska Jolanta Wierzba Jacek Jasiecki Bartosz Wasag |
| author_sort | Natalia Krawczynska |
| collection | DOAJ |
| description | Abstract Background Cornelia de Lange syndrome (CdLS), a rare, multisystemic disorder, has been linked to genetic alterations in NIPBL, SMC1A, SMC3, HDAC8, and RAD21 genes. Approximately 60% of CdLS patients harbor various NIPBL variants. Genetic changes predicted to affect NIPBL gene splicing represent 15% of all NIPBL genetic abnormalities. Yet, only a few studies have investigated the molecular consequences of such variants. Case presentation This study reports two novel, intronic NIPBL genetic variants in unrelated CdLS patients with the characteristic phenotype. A c.6954 + 3A > C substitution and a c.5862 + 1delG deletion were identified, one of each, in a 6 year-old boy and 39 month-old girl. Further studies confirmed that both variants introduce premature termination codons, resulting in the formation of truncated proteins p.(Ser2255LeufsTer20) and p.(Leu1955Ter), respectively. Conclusion Single nucleotide alterations located within the conserved splice-donor site of intronic regions of the NIPBL gene can give rise to a premature termination of the translation and cause significant changes in the sequence of mRNA transcripts and NIPBL protein structure and function. The latter underline development of Cornelia de Lange syndrome phenotype. |
| first_indexed | 2024-12-14T09:41:20Z |
| format | Article |
| id | doaj.art-2b62cbb3e3424a28a538fbf450c51344 |
| institution | Directory Open Access Journal |
| issn | 1471-2350 |
| language | English |
| last_indexed | 2024-12-14T09:41:20Z |
| publishDate | 2019-01-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Medical Genetics |
| spelling | doaj.art-2b62cbb3e3424a28a538fbf450c513442022-12-21T23:07:46ZengBMCBMC Medical Genetics1471-23502019-01-012011610.1186/s12881-018-0738-yMolecular characterization of two novel intronic variants of NIPBL gene detected in unrelated Cornelia de Lange syndrome patientsNatalia Krawczynska0Jolanta Wierzba1Jacek Jasiecki2Bartosz Wasag3Department of Biology and Medical Genetics, Medical University of GdanskDepartment of Pediatrics, Hematology and Oncology, Medical University of GdanskDepartment of Pharmaceutical Microbiology, Medical University of GdanskDepartment of Biology and Medical Genetics, Medical University of GdanskAbstract Background Cornelia de Lange syndrome (CdLS), a rare, multisystemic disorder, has been linked to genetic alterations in NIPBL, SMC1A, SMC3, HDAC8, and RAD21 genes. Approximately 60% of CdLS patients harbor various NIPBL variants. Genetic changes predicted to affect NIPBL gene splicing represent 15% of all NIPBL genetic abnormalities. Yet, only a few studies have investigated the molecular consequences of such variants. Case presentation This study reports two novel, intronic NIPBL genetic variants in unrelated CdLS patients with the characteristic phenotype. A c.6954 + 3A > C substitution and a c.5862 + 1delG deletion were identified, one of each, in a 6 year-old boy and 39 month-old girl. Further studies confirmed that both variants introduce premature termination codons, resulting in the formation of truncated proteins p.(Ser2255LeufsTer20) and p.(Leu1955Ter), respectively. Conclusion Single nucleotide alterations located within the conserved splice-donor site of intronic regions of the NIPBL gene can give rise to a premature termination of the translation and cause significant changes in the sequence of mRNA transcripts and NIPBL protein structure and function. The latter underline development of Cornelia de Lange syndrome phenotype.http://link.springer.com/article/10.1186/s12881-018-0738-yCdLSCornelia de Lange syndromeNIPBL geneSplice-site variantsNext generation sequencing |
| spellingShingle | Natalia Krawczynska Jolanta Wierzba Jacek Jasiecki Bartosz Wasag Molecular characterization of two novel intronic variants of NIPBL gene detected in unrelated Cornelia de Lange syndrome patients BMC Medical Genetics CdLS Cornelia de Lange syndrome NIPBL gene Splice-site variants Next generation sequencing |
| title | Molecular characterization of two novel intronic variants of NIPBL gene detected in unrelated Cornelia de Lange syndrome patients |
| title_full | Molecular characterization of two novel intronic variants of NIPBL gene detected in unrelated Cornelia de Lange syndrome patients |
| title_fullStr | Molecular characterization of two novel intronic variants of NIPBL gene detected in unrelated Cornelia de Lange syndrome patients |
| title_full_unstemmed | Molecular characterization of two novel intronic variants of NIPBL gene detected in unrelated Cornelia de Lange syndrome patients |
| title_short | Molecular characterization of two novel intronic variants of NIPBL gene detected in unrelated Cornelia de Lange syndrome patients |
| title_sort | molecular characterization of two novel intronic variants of nipbl gene detected in unrelated cornelia de lange syndrome patients |
| topic | CdLS Cornelia de Lange syndrome NIPBL gene Splice-site variants Next generation sequencing |
| url | http://link.springer.com/article/10.1186/s12881-018-0738-y |
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