A novel deep intronic variant strongly associates with Alkaptonuria.

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Tsai, I-Jung 
Chiu, Pao-Chin 

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.

31 Biological Sciences, 32 Biomedical and Clinical Sciences, 3105 Genetics, Heart Disease, Cardiovascular, Biotechnology, Genetic Testing, Neurodegenerative, Genetics, 2.1 Biological and endogenous factors, 2 Aetiology
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NPJ Genom Med
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Springer Science and Business Media LLC
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)