Characterisation of CDKL5 Transcript Isoforms in Human and Mouse.
Mutations in the X-linked Cyclin-Dependent Kinase-Like 5 gene (CDKL5) cause early onset infantile spasms and subsequent severe developmental delay in affected children. Deleterious mutations have been reported to occur throughout the CDKL5 coding region. Several studies point to a complex CDKL5 gene...
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doaj-9a584d0583cf4017904a95080225be632020-11-24T21:35:37ZengPublic Library of Science (PLoS)PLoS ONE1932-62032016-01-01116e015775810.1371/journal.pone.0157758Characterisation of CDKL5 Transcript Isoforms in Human and Mouse.Ralph D HectorOwen DandoNicoletta LandsbergerCharlotte Kilstrup-NielsenPeter C KindMark E S BaileyStuart R CobbMutations in the X-linked Cyclin-Dependent Kinase-Like 5 gene (CDKL5) cause early onset infantile spasms and subsequent severe developmental delay in affected children. Deleterious mutations have been reported to occur throughout the CDKL5 coding region. Several studies point to a complex CDKL5 gene structure in terms of exon usage and transcript expression. Improvements in molecular diagnosis and more extensive research into the neurobiology of CDKL5 and pathophysiology of CDKL5 disorders necessitate an updated analysis of the gene. In this study, we have analysed human and mouse CDKL5 transcript patterns both bioinformatically and experimentally. We have characterised the predominant brain isoform of CDKL5, a 9.7 kb transcript comprised of 18 exons with a large 6.6 kb 3'-untranslated region (UTR), which we name hCDKL5_1. In addition we describe new exonic regions and a range of novel splice and UTR isoforms. This has enabled the description of an updated gene model in both species and a standardised nomenclature system for CDKL5 transcripts. Profiling revealed tissue- and brain development stage-specific differences in expression between transcript isoforms. These findings provide an essential backdrop for the diagnosis of CDKL5-related disorders, for investigations into the basic biology of this gene and its protein products, and for the rational design of gene-based and molecular therapies for these disorders.http://europepmc.org/articles/PMC4912119?pdf=render |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Ralph D Hector Owen Dando Nicoletta Landsberger Charlotte Kilstrup-Nielsen Peter C Kind Mark E S Bailey Stuart R Cobb |
spellingShingle |
Ralph D Hector Owen Dando Nicoletta Landsberger Charlotte Kilstrup-Nielsen Peter C Kind Mark E S Bailey Stuart R Cobb Characterisation of CDKL5 Transcript Isoforms in Human and Mouse. PLoS ONE |
author_facet |
Ralph D Hector Owen Dando Nicoletta Landsberger Charlotte Kilstrup-Nielsen Peter C Kind Mark E S Bailey Stuart R Cobb |
author_sort |
Ralph D Hector |
title |
Characterisation of CDKL5 Transcript Isoforms in Human and Mouse. |
title_short |
Characterisation of CDKL5 Transcript Isoforms in Human and Mouse. |
title_full |
Characterisation of CDKL5 Transcript Isoforms in Human and Mouse. |
title_fullStr |
Characterisation of CDKL5 Transcript Isoforms in Human and Mouse. |
title_full_unstemmed |
Characterisation of CDKL5 Transcript Isoforms in Human and Mouse. |
title_sort |
characterisation of cdkl5 transcript isoforms in human and mouse. |
publisher |
Public Library of Science (PLoS) |
series |
PLoS ONE |
issn |
1932-6203 |
publishDate |
2016-01-01 |
description |
Mutations in the X-linked Cyclin-Dependent Kinase-Like 5 gene (CDKL5) cause early onset infantile spasms and subsequent severe developmental delay in affected children. Deleterious mutations have been reported to occur throughout the CDKL5 coding region. Several studies point to a complex CDKL5 gene structure in terms of exon usage and transcript expression. Improvements in molecular diagnosis and more extensive research into the neurobiology of CDKL5 and pathophysiology of CDKL5 disorders necessitate an updated analysis of the gene. In this study, we have analysed human and mouse CDKL5 transcript patterns both bioinformatically and experimentally. We have characterised the predominant brain isoform of CDKL5, a 9.7 kb transcript comprised of 18 exons with a large 6.6 kb 3'-untranslated region (UTR), which we name hCDKL5_1. In addition we describe new exonic regions and a range of novel splice and UTR isoforms. This has enabled the description of an updated gene model in both species and a standardised nomenclature system for CDKL5 transcripts. Profiling revealed tissue- and brain development stage-specific differences in expression between transcript isoforms. These findings provide an essential backdrop for the diagnosis of CDKL5-related disorders, for investigations into the basic biology of this gene and its protein products, and for the rational design of gene-based and molecular therapies for these disorders. |
url |
http://europepmc.org/articles/PMC4912119?pdf=render |
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