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Open Access 01-12-2019 | Choanal Atresia | Case report

A novel CHD7 variant disrupting acceptor splice site in a patient with mild features of CHARGE syndrome: a case report

Authors: Evelina Siavrienė, Gunda Petraitytė, Violeta Mikštienė, Tautvydas Rančelis, Živilė Maldžienė, Aušra Morkūnienė, Jekaterina Byčkova, Algirdas Utkus, Vaidutis Kučinskas, Eglė Preikšaitienė

Published in: BMC Medical Genetics | Issue 1/2019

Abstract

Background

CHARGE syndrome (MIM# 214800)—which is characterised by a number of congenital anomalies including coloboma, ear anomalies, deafness, facial anomalies, heart defects, atresia choanae, genital hypoplasia, growth retardation, and developmental delay—is caused by a heterozygous variant in the CHD7 (MIM# 608892) gene located on chromosome 8q12. We report the identification of a novel c.5535-1G > A variant in CHD7 and provide the evaluation of its effect on pre-mRNA splicing.

Case presentation

In this study, we report on a female presenting features of CHARGE syndrome. A novel heterozygous CHD7 variant c.5535-1G > A located in the acceptor splice site of intron 26 was identified in the proband’s DNA sample after analysis of whole exome sequencing data. In silico predictions indicating that the variant is probably pathogenic by affecting pre-mRNA splicing were verified by genetic analysis based on reverse transcription of the patient’s RNA followed by PCR amplifications performed on synthesised cDNA and Sanger sequencing. Sanger sequencing of cDNA revealed that the c.5535-1G > A variant disrupts the original acceptor splice site and activates a cryptic splice site only one nucleotide downstream of the pathogenic variant site. This change causes the omission of the first nucleotide of exon 27, leading to a frameshift in the mRNA of the CHD7 gene. Our results suggest that the alteration induces the premature truncation of the CHD7 protein (UniProtKB: Q9P2D1), thus resulting in CHARGE syndrome.

Conclusion

Genetic analysis of novel splice site variant underlines its importance for studying the pathogenic splicing mechanism as well as for confirming a diagnosis.

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Title: A novel CHD7 variant disrupting acceptor splice site in a patient with mild features of CHARGE syndrome: a case report
Authors: Evelina Siavrienė
Gunda Petraitytė
Violeta Mikštienė
Tautvydas Rančelis
Živilė Maldžienė
Aušra Morkūnienė
Jekaterina Byčkova
Algirdas Utkus
Vaidutis Kučinskas
Eglė Preikšaitienė
Publication date: 01-12-2019
Publisher: BioMed Central
Keywords: Choanal Atresia
Polymerase Chain Reaction
Published in: BMC Medical Genetics / Issue 1/2019
Electronic ISSN: 1471-2350
DOI: https://doi.org/10.1186/s12881-019-0859-y

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A novel CHD7 variant disrupting acceptor splice site in a patient with mild features of CHARGE syndrome: a case report

Abstract

Background

Case presentation

Conclusion

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Case presentation

Conclusion

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