CELSR2 is a candidate susceptibility gene in idiopathic scoliosis.
A Swedish pedigree with an autosomal dominant inheritance of idiopathic scoliosis was initially studied by genetic linkage analysis, prioritising genomic regions for further analysis. This revealed a locus on chromosome 1 with a putative risk haplotype shared by all affected individuals. Two affecte...
Main Authors: | , , , , , , , , , , , , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
Public Library of Science (PLoS)
2017-01-01
|
Series: | PLoS ONE |
Online Access: | https://doi.org/10.1371/journal.pone.0189591 |
id |
doaj-9574148f9bf84766ab16c3ef7fd66273 |
---|---|
record_format |
Article |
spelling |
doaj-9574148f9bf84766ab16c3ef7fd662732021-03-03T21:27:25ZengPublic Library of Science (PLoS)PLoS ONE1932-62032017-01-011212e018959110.1371/journal.pone.0189591CELSR2 is a candidate susceptibility gene in idiopathic scoliosis.Elisabet EinarsdottirAnna GrauersJingwen WangHong JiaoStefan A EscherAina DanielssonAne SimonyMikkel AndersenMikkel AndersenSteen Bach ChristensenKristina ÅkessonIkuyo KouAnas M KhanshourAcke OhlinCarol WiseShiro IkegawaJuha KerePaul GerdhemA Swedish pedigree with an autosomal dominant inheritance of idiopathic scoliosis was initially studied by genetic linkage analysis, prioritising genomic regions for further analysis. This revealed a locus on chromosome 1 with a putative risk haplotype shared by all affected individuals. Two affected individuals were subsequently exome-sequenced, identifying a rare, non-synonymous variant in the CELSR2 gene. This variant is rs141489111, a c.G6859A change in exon 21 (NM_001408), leading to a predicted p.V2287I (NP_001399.1) change. This variant was found in all affected members of the pedigree, but showed reduced penetrance. Analysis of tagging variants in CELSR1-3 in a set of 1739 Swedish-Danish scoliosis cases and 1812 controls revealed significant association (p = 0.0001) to rs2281894, a common synonymous variant in CELSR2. This association was not replicated in case-control cohorts from Japan and the US. No association was found to variants in CELSR1 or CELSR3. Our findings suggest a rare variant in CELSR2 as causative for idiopathic scoliosis in a family with dominant segregation and further highlight common variation in CELSR2 in general susceptibility to idiopathic scoliosis in the Swedish-Danish population. Both variants are located in the highly conserved GAIN protein domain, which is necessary for the auto-proteolysis of CELSR2, suggesting its functional importance.https://doi.org/10.1371/journal.pone.0189591 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Elisabet Einarsdottir Anna Grauers Jingwen Wang Hong Jiao Stefan A Escher Aina Danielsson Ane Simony Mikkel Andersen Mikkel Andersen Steen Bach Christensen Kristina Åkesson Ikuyo Kou Anas M Khanshour Acke Ohlin Carol Wise Shiro Ikegawa Juha Kere Paul Gerdhem |
spellingShingle |
Elisabet Einarsdottir Anna Grauers Jingwen Wang Hong Jiao Stefan A Escher Aina Danielsson Ane Simony Mikkel Andersen Mikkel Andersen Steen Bach Christensen Kristina Åkesson Ikuyo Kou Anas M Khanshour Acke Ohlin Carol Wise Shiro Ikegawa Juha Kere Paul Gerdhem CELSR2 is a candidate susceptibility gene in idiopathic scoliosis. PLoS ONE |
author_facet |
Elisabet Einarsdottir Anna Grauers Jingwen Wang Hong Jiao Stefan A Escher Aina Danielsson Ane Simony Mikkel Andersen Mikkel Andersen Steen Bach Christensen Kristina Åkesson Ikuyo Kou Anas M Khanshour Acke Ohlin Carol Wise Shiro Ikegawa Juha Kere Paul Gerdhem |
author_sort |
Elisabet Einarsdottir |
title |
CELSR2 is a candidate susceptibility gene in idiopathic scoliosis. |
title_short |
CELSR2 is a candidate susceptibility gene in idiopathic scoliosis. |
title_full |
CELSR2 is a candidate susceptibility gene in idiopathic scoliosis. |
title_fullStr |
CELSR2 is a candidate susceptibility gene in idiopathic scoliosis. |
title_full_unstemmed |
CELSR2 is a candidate susceptibility gene in idiopathic scoliosis. |
title_sort |
celsr2 is a candidate susceptibility gene in idiopathic scoliosis. |
publisher |
Public Library of Science (PLoS) |
series |
PLoS ONE |
issn |
1932-6203 |
publishDate |
2017-01-01 |
description |
A Swedish pedigree with an autosomal dominant inheritance of idiopathic scoliosis was initially studied by genetic linkage analysis, prioritising genomic regions for further analysis. This revealed a locus on chromosome 1 with a putative risk haplotype shared by all affected individuals. Two affected individuals were subsequently exome-sequenced, identifying a rare, non-synonymous variant in the CELSR2 gene. This variant is rs141489111, a c.G6859A change in exon 21 (NM_001408), leading to a predicted p.V2287I (NP_001399.1) change. This variant was found in all affected members of the pedigree, but showed reduced penetrance. Analysis of tagging variants in CELSR1-3 in a set of 1739 Swedish-Danish scoliosis cases and 1812 controls revealed significant association (p = 0.0001) to rs2281894, a common synonymous variant in CELSR2. This association was not replicated in case-control cohorts from Japan and the US. No association was found to variants in CELSR1 or CELSR3. Our findings suggest a rare variant in CELSR2 as causative for idiopathic scoliosis in a family with dominant segregation and further highlight common variation in CELSR2 in general susceptibility to idiopathic scoliosis in the Swedish-Danish population. Both variants are located in the highly conserved GAIN protein domain, which is necessary for the auto-proteolysis of CELSR2, suggesting its functional importance. |
url |
https://doi.org/10.1371/journal.pone.0189591 |
work_keys_str_mv |
AT elisabeteinarsdottir celsr2isacandidatesusceptibilitygeneinidiopathicscoliosis AT annagrauers celsr2isacandidatesusceptibilitygeneinidiopathicscoliosis AT jingwenwang celsr2isacandidatesusceptibilitygeneinidiopathicscoliosis AT hongjiao celsr2isacandidatesusceptibilitygeneinidiopathicscoliosis AT stefanaescher celsr2isacandidatesusceptibilitygeneinidiopathicscoliosis AT ainadanielsson celsr2isacandidatesusceptibilitygeneinidiopathicscoliosis AT anesimony celsr2isacandidatesusceptibilitygeneinidiopathicscoliosis AT mikkelandersen celsr2isacandidatesusceptibilitygeneinidiopathicscoliosis AT mikkelandersen celsr2isacandidatesusceptibilitygeneinidiopathicscoliosis AT steenbachchristensen celsr2isacandidatesusceptibilitygeneinidiopathicscoliosis AT kristinaakesson celsr2isacandidatesusceptibilitygeneinidiopathicscoliosis AT ikuyokou celsr2isacandidatesusceptibilitygeneinidiopathicscoliosis AT anasmkhanshour celsr2isacandidatesusceptibilitygeneinidiopathicscoliosis AT ackeohlin celsr2isacandidatesusceptibilitygeneinidiopathicscoliosis AT carolwise celsr2isacandidatesusceptibilitygeneinidiopathicscoliosis AT shiroikegawa celsr2isacandidatesusceptibilitygeneinidiopathicscoliosis AT juhakere celsr2isacandidatesusceptibilitygeneinidiopathicscoliosis AT paulgerdhem celsr2isacandidatesusceptibilitygeneinidiopathicscoliosis |
_version_ |
1714816745982656512 |