A Novel ERCC6 Splicing Variant Associated with a Mild Cockayne Syndrome Phenotype

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dc.authoridAkinci, Aysehan/0000-0001-7267-9444
dc.authoridSigirci, Ahmet/0000-0001-9221-0002
dc.authoridAndrew, Shayne/0000-0001-7226-7757
dc.authorwosidAkinci, Aysehan/AAC-6847-2021
dc.authorwosidSigirci, Ahmet/ABG-7387-2020
dc.contributor.authorSwartz, Jonathan M.
dc.contributor.authorAkinci, Aysehan
dc.contributor.authorAndrew, Shayne F.
dc.contributor.authorSigirci, Ahmet
dc.contributor.authorHirschhorn, Joel N.
dc.contributor.authorRosenfeld, Ron G.
dc.contributor.authorDauber, Andrew
dc.date.accessioned2024-08-04T20:39:54Z
dc.date.available2024-08-04T20:39:54Z
dc.date.issued2014
dc.departmentİnönü Üniversitesien_US
dc.description.abstractBackground: Cockayne syndrome is an autosomal recessive, heterogeneous syndrome with classical features, including short stature, microcephaly, developmental delay, neuropathy, and photosensitivity. New genomic approaches offer improved molecular diagnostic potential. Methods: Whole-exome sequencing was employed to study a consanguineous extended family with severe short stature and variable presentations of peripheral neuropathy, lipoatrophy, photosensitivity, webbed neck, and hirsutism. Results: We identified a novel homozygous ERCC6 variant at the donor splice site of intron 9 (c.1992 + 3A>G), which was predicted to only slightly perturb splicing efficiencies. Assessment of primary fibroblast-derived mRNAs, however, revealed a dominant splicing species that utilized an unsuspected putative donor splice site within exon 9, resulting in predicted early protein termination (p.Arg637Serfs*34). Conclusions: We describe a new splicing ERCC6 defect causal of Cockayne syndrome. The application of exome sequence analysis was integral to diagnosis, given the complexity of phenotypic presentation in the affected family members. The novel splicing defect, furthermore, illustrates how a seemingly minor change in the relative strength of a splice site can have significant biological consequences. (C) 2014 S. Karger AG, Baselen_US
dc.description.sponsorshipNational Institutes of Health [1K23HD073351, 5T32DK007699-32]; Pediatric Endocrine Society Clinical Scholar Awarden_US
dc.description.sponsorshipThis work was supported by National Institutes of Health grants 1K23HD073351 (to A.D.) and 5T32DK007699-32 (to J.S.), as well as the Pediatric Endocrine Society Clinical Scholar Award (to A.D.).en_US
dc.identifier.doi10.1159/000368192
dc.identifier.endpage352en_US
dc.identifier.issn1663-2818
dc.identifier.issn1663-2826
dc.identifier.issue5en_US
dc.identifier.pmid25376329en_US
dc.identifier.scopus2-s2.0-84909953027en_US
dc.identifier.scopusqualityQ1en_US
dc.identifier.startpage344en_US
dc.identifier.urihttps://doi.org/10.1159/000368192
dc.identifier.urihttps://hdl.handle.net/11616/96589
dc.identifier.volume82en_US
dc.identifier.wosWOS:000345449800009en_US
dc.identifier.wosqualityQ2en_US
dc.indekslendigikaynakWeb of Scienceen_US
dc.indekslendigikaynakScopusen_US
dc.indekslendigikaynakPubMeden_US
dc.language.isoenen_US
dc.publisherKargeren_US
dc.relation.ispartofHormone Research in Paediatricsen_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıen_US
dc.rightsinfo:eu-repo/semantics/openAccessen_US
dc.subjectERCC6 varianten_US
dc.subjectCockayne syndromeen_US
dc.subjectShort statureen_US
dc.titleA Novel ERCC6 Splicing Variant Associated with a Mild Cockayne Syndrome Phenotypeen_US
dc.typeArticleen_US

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