Detailed molecular characterization of a novel IDS exonic mutation associated with multiple pseudoexon activation

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00209775%3A_____%2F17%3AN0000010" target="_blank" >RIV/00209775:_____/17:N0000010 - isvavai.cz</a>

Alternative codes found

RIV/00216224:14740/17:00095653 RIV/00216208:11110/17:10362076

Result on the web

<a href="https://link.springer.com/article/10.1007/s00109-016-1484-2" target="_blank" >https://link.springer.com/article/10.1007/s00109-016-1484-2</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1007/s00109-016-1484-2" target="_blank" >10.1007/s00109-016-1484-2</a>

Result language

angličtina

Original language name

Detailed molecular characterization of a novel IDS exonic mutation associated with multiple pseudoexon activation

Original language description

Mutations affecting splicing underlie the development of many human genetic diseases, but rather rarely through mechanisms of pseudoexon activation. Here, we describe a novel c.1092T>A mutation in the iduronate-2-sulfatase (IDS) gene detected in a patient with significantly decreased IDS activity and a clinical diagnosis of mild mucopolysaccharidosis II form. The mutation created an exonic de novo acceptor splice site and resulted in a complex splicing pattern with multiple pseudoexon activation in the patient’s fibroblasts. Using an extensive series of minigene splicing experiments, we showed that the competition itself between the de novo and authentic splice site led to the bypass of the authentic one. This event then resulted in activation of several cryptic acceptor and donor sites in the upstream intron. As this was an unexpected and previously unreported mechanism of aberrant pseudoexon inclusion, we systematically analysed and disproved that the patient’s mutation induced any relevant change in surrounding splicing regulatory elements. Interestingly, all pseudoexons included in the mature transcripts overlapped with the IDS alternative terminal exon 7b suggesting that this sequence represents a key element in the IDS pre-mRNA architecture. These findings extend the spectrum of mechanisms enabling pseudoexon activation and underscore the complexity of mutation-induced splicing aberrations.

Czech name

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Czech description

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Type

J_ost - Miscellaneous article in a specialist periodical

CEP classification

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OECD FORD branch

10608 - Biochemistry and molecular biology

Project

Result was created during the realization of more than one project. More information in the Projects tab.

Continuities

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Publication year

2017

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

Journal of Molecular Medicine

ISSN

0946-2716

e-ISSN

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Volume of the periodical

95

Issue of the periodical within the volume

3

Country of publishing house

DE - GERMANY

Number of pages

11

Pages from-to

299-309

UT code for WoS article

000395072600007

EID of the result in the Scopus database

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