A novel deep intronic variant strongly associates with Alkaptonuria.
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Authors
Tsai, I-Jung
Chiu, Pao-Chin
Huang, Yu-Hsuan
Lin, Yi-Lin
Hwu, Wuh-Liang
Publication Date
2021-10-22Journal Title
NPJ Genom Med
ISSN
2056-7944
Publisher
Springer Science and Business Media LLC
Volume
6
Issue
1
Language
eng
Type
Article
This Version
VoR
Metadata
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Lai, C., Tsai, I., Chiu, P., Ascher, D. B., Chien, Y., Huang, Y., Lin, Y., et al. (2021). A novel deep intronic variant strongly associates with Alkaptonuria.. NPJ Genom Med, 6 (1) https://doi.org/10.1038/s41525-021-00252-2
Abstract
Alkaptonuria 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.
Sponsorship
National Taiwan University Hospital (NTUH 105-002959)
National Taiwan University Hospital (NTUH) (NTUH 105-002959)
Ministry of Science and Technology, Taiwan (Ministry of Science and Technology of Taiwan) (107-2314-B-002 -164 -MY3)
Ministry of Science and Technology, Taiwan (107-2314-B-002 -164 -MY3)
Identifiers
PMC8536767, 34686677
External DOI: https://doi.org/10.1038/s41525-021-00252-2
This record's URL: https://www.repository.cam.ac.uk/handle/1810/332150
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