Titre
De novo splice site variant of ARID1B associated with pathogenesis of Coffin-Siris syndrome.
Type
article
Institution
UNIL/CHUV/Unisanté + institutions partenaires
Périodique
Auteur(s)
Pranckėnienė, L.
Auteure/Auteur
Siavrienė, E.
Auteure/Auteur
Gueneau, L.
Auteure/Auteur
Preikšaitienė, E.
Auteure/Auteur
Mikštienė, V.
Auteure/Auteur
Reymond, A.
Auteure/Auteur
Kučinskas, V.
Auteure/Auteur
Liens vers les personnes
Liens vers les unités
ISSN
2324-9269
Statut éditorial
Publié
Date de publication
2019-12
Volume
7
Numéro
12
Première page
e1006
Peer-reviewed
Oui
Langue
anglais
Notes
Publication types: Case Reports ; Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Publication Status: ppublish
Résumé
Coffin-Siris syndrome is an extremely rare syndrome associated with developmental and congenital anomalies. It is caused by heterozygous pathogenic variants of ARID1A, ARID1B, SMARCA4, SMARCB1, SMARCE1, and SOX11.
This case study presents the whole exome sequencing of a patient with characteristic clinical features of Coffin-Siris syndrome. Analysis included Sanger sequencing of complementary DNA and bioinformatic analysis of the variant.
Analysis of cDNA Sanger sequencing data revealed that the donor splice site variant led to skipping of exon 19. Further, bioinformatic analysis predicted abnormal splicing in a translational frameshift of 11 amino acids and the creation of a premature termination codon. Results found a novel de novo splice site variant c.5025+2T>C in the ARID1B and truncated 1 633 amino acid protein NP_065783.3:p. (Thr1633Valfs*11).
Truncated ARID1B resulted in loss of the BAF250 domain, which is part of SWI/SNF-like ATP-dependent chromatin remodeling complex. The severe clinical manifestation presented by the proband was attributed to the disappearance of the BAF250 domain in the ARID1B protein. Our finding provides strong evidence that this pathogenic variant of exon 19 caused a frameshift mutation in the ARID1B at the terminal exon, resulting in the expression of a severe phenotype of CSS.
This case study presents the whole exome sequencing of a patient with characteristic clinical features of Coffin-Siris syndrome. Analysis included Sanger sequencing of complementary DNA and bioinformatic analysis of the variant.
Analysis of cDNA Sanger sequencing data revealed that the donor splice site variant led to skipping of exon 19. Further, bioinformatic analysis predicted abnormal splicing in a translational frameshift of 11 amino acids and the creation of a premature termination codon. Results found a novel de novo splice site variant c.5025+2T>C in the ARID1B and truncated 1 633 amino acid protein NP_065783.3:p. (Thr1633Valfs*11).
Truncated ARID1B resulted in loss of the BAF250 domain, which is part of SWI/SNF-like ATP-dependent chromatin remodeling complex. The severe clinical manifestation presented by the proband was attributed to the disappearance of the BAF250 domain in the ARID1B protein. Our finding provides strong evidence that this pathogenic variant of exon 19 caused a frameshift mutation in the ARID1B at the terminal exon, resulting in the expression of a severe phenotype of CSS.
Sujets
PID Serval
serval:BIB_F17EED3A2B89
PMID
Open Access
Oui
Date de création
2019-10-21T13:41:41.171Z
Date de création dans IRIS
2025-05-21T07:03:12Z
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Nom
31628733_BIB_F17EED3A2B89.pdf
Version du manuscrit
published
Licence
https://creativecommons.org/licenses/by-nc-nd/4.0
Taille
767.5 KB
Format
Adobe PDF
PID Serval
serval:BIB_F17EED3A2B89.P001
URN
urn:nbn:ch:serval-BIB_F17EED3A2B890
Somme de contrôle
(MD5):7c2ca0deeb67844f23b5137a3e0859a0