A novel deep intronic variant strongly associates with Alkaptonuria.

cam.issuedOnline2021-10-22
dc.contributor.authorLai, Chien-Yi
dc.contributor.authorTsai, I-Jung
dc.contributor.authorChiu, Pao-Chin
dc.contributor.authorAscher, David B
dc.contributor.authorChien, Yin-Hsiu
dc.contributor.authorHuang, Yu-Hsuan
dc.contributor.authorLin, Yi-Lin
dc.contributor.authorHwu, Wuh-Liang
dc.contributor.authorLee, Ni-Chung
dc.contributor.orcidLai, Chien-Yi [0000-0002-5962-8869]
dc.contributor.orcidAscher, David B [0000-0003-2948-2413]
dc.contributor.orcidChien, Yin-Hsiu [0000-0001-8802-5728]
dc.contributor.orcidLee, Ni-Chung [0000-0002-5011-7499]
dc.date.accessioned2021-10-22T15:51:08Z
dc.date.available2021-10-22T15:51:08Z
dc.date.issued2021-10-22
dc.date.submitted2021-02-07
dc.date.updated2021-10-22T15:51:07Z
dc.description.abstractAlkaptonuria is a rare autosomal recessive inherited disorder of tyrosine metabolism, which causes ochronosis, arthropathy, cardiac valvular calcification, and urolithiasis. The epidemiology of alkaptonuria in East Asia is not clear. In this study, patients diagnosed with alkaptonuria from January 2010 to June 2020 were reviewed. Their clinical and molecular features were further compared with those of patients from other countries. Three patients were found to have alkaptonuria. Mutation analyses of the homogentisate 1,2-dioxygenase gene (HGD) showed four novel variants c.16-2063 A > C, p.(Thr196Ile), p.(Gly344AspfsTer25), and p.(Gly362Arg) in six mutated alleles (83.3%). RNA sequencing revealed that c.16-2063 A > C activates a cryptic exon, causing protein truncation p.(Tyr5_Ile6insValTer17). A literature search identified another 6 patients with alkaptonuria in East Asia; including our cases, 13 of the 18 mutated alleles have not been reported elsewhere in the world. Alkaptonuria is rare in Taiwan and East Asia, with HGD variants being mostly novel and private.
dc.identifier.doi10.17863/CAM.77217
dc.identifier.eissn2056-7944
dc.identifier.issn2056-7944
dc.identifier.others41525-021-00252-2
dc.identifier.other252
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/329772
dc.languageen
dc.publisherSpringer Science and Business Media LLC
dc.subjectArticle
dc.subject/692/4017
dc.subject/692/699/317
dc.subjectarticle
dc.titleA novel deep intronic variant strongly associates with Alkaptonuria.
dc.typeArticle
dcterms.dateAccepted2021-10-04
prism.issueIdentifier1
prism.publicationNameNPJ Genom Med
prism.volume6
pubs.funder-project-idMinistry of Science and Technology, Taiwan (Ministry of Science and Technology of Taiwan) (107-2314-B-002 -164 -MY3)
pubs.funder-project-idNational Taiwan University Hospital (NTUH) (NTUH 105-002959, NTUH 105-002959)
rioxxterms.licenseref.urihttp://creativecommons.org/licenses/by/4.0/
rioxxterms.versionVoR
rioxxterms.versionofrecord10.1038/s41525-021-00252-2
Files
Original bundle
Now showing 1 - 4 of 4
No Thumbnail Available
Name:
41525_2021_Article_252_nlm.xml
Size:
67.44 KB
Format:
Extensible Markup Language
Licence
http://creativecommons.org/licenses/by/4.0/
Loading...
Thumbnail Image
Name:
41525_2021_Article_252.pdf
Size:
1.82 MB
Format:
Adobe Portable Document Format
Licence
http://creativecommons.org/licenses/by/4.0/
Loading...
Thumbnail Image
Name:
41525_2021_252_MOESM1_ESM.pdf
Size:
180.72 KB
Format:
Adobe Portable Document Format
Licence
http://creativecommons.org/licenses/by/4.0/
Loading...
Thumbnail Image
Name:
41525_2021_252_MOESM2_ESM.pdf
Size:
75.53 KB
Format:
Adobe Portable Document Format
Licence
http://creativecommons.org/licenses/by/4.0/