A novel deep intronic variant strongly associates with Alkaptonuria

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 2...

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Bibliographic Details
Published in:Npj genomic medicine 2021-10, Vol.6 (1), p.89-89, Article 89
Main Authors: Lai, Chien-Yi, Tsai, I-Jung, Chiu, Pao-Chin, Ascher, David B., Chien, Yin-Hsiu, Huang, Yu-Hsuan, Lin, Yi-Lin, Hwu, Wuh-Liang, Lee, Ni-Chung
Format: Article
Language:English
Subjects:
692/4017
692/699/317
Age
Alkaptonuria
Alleles
Binding sites
Biochemistry
Bioinformatics
Biology
Biomedical and Life Sciences
Biomedicine
Calcification
Calcification (ectopic)
Epidemiology
Gene Function
Gene Therapy
Hereditary diseases
Homogentisate 1,2-dioxygenase
Hospitals
Human Genetics
Internal Medicine
Lithiasis
Mutation
Ochronosis
Patients
Pediatrics
Proteins
Tyrosine
Urinary tract diseases
Urine
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Summary: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.
ISSN:2056-7944
2056-7944
DOI:10.1038/s41525-021-00252-2