Two novel mutations in the homogentisate-1,2-dioxygenase gene identified in Chinese Han Child with Alkaptonuria

Hongying Li; Kaihui Zhang; Qun Xu; Lixia Ma; Xin Lv; Ruopeng Sun

doi:10.1515/jpem-2014-0122

Article

Two novel mutations in the homogentisate-1,2-dioxygenase gene identified in Chinese Han Child with Alkaptonuria

Hongying Li , Kaihui Zhang , Qun Xu , Lixia Ma , Xin Lv and Ruopeng Sun

Published/Copyright: August 12, 2014

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From the journal Journal of Pediatric Endocrinology and Metabolism Volume 28 Issue 3-4

Abstract

Alkaptonuria (AKU) is an autosomal recessive disorder of tyrosine metabolism, which is caused by a defect in the enzyme homogentisate 1,2-dioxygenase (HGD) with subsequent accumulation of homogentisic acid. Presently, more than 100 HGD mutations have been identified as the cause of the inborn error of metabolism across different populations worldwide. However, the HGD mutation is very rarely reported in Asia, especially China. In this study, we present mutational analyses of HGD gene in one Chinese Han child with AKU, which had been identified by gas chromatography-mass spectrometry detection of organic acids in urine samples. PCR and DNA sequencing of the entire coding region as well as exon-intron boundaries of HGD have been performed. Two novel mutations were identified in the HGD gene in this AKU case, a frameshift mutation of c.115delG in exon 3 and the splicing mutation of IVS5+3 A>C, a donor splice site of the exon 5 and exon-intron junction. The identification of these mutations in this study further expands the spectrum of known HGD gene mutations and contributes to prenatal molecular diagnosis of AKU.

Keywords: alkaptonuria; Chinese; homogentisate 1,2-dioxygenase; mutation

Corresponding authors: Ruopeng Sun, Department of Pediatrics, Qilu Hospital of Shandong University, Jinan, China, Phone: +86-531-813-09096, Fax: +86- 531-879-64257, E-mail: sunruopengjn@163.com; and Xin Lv, Institute of Pediatric Research, Qilu Children’s Hospital of Shandong University, Jinan, Shandong, China, E-mail: kokoxin25@163.com

Acknowledgments

The authors gratefully acknowledge the patient with AKU for their participation and cooperation in this study. This work was supported financially by the Fund for Outstanding Young Scientist in Shandong Province (Project Nos. BS2012YY001) and the Development Plan of Science and Technology in Shandong Province (Project Nos. 2012G0021855).

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Received: 2014-3-16

Accepted: 2014-7-9

Published Online: 2014-8-12

Published in Print: 2015-3-1

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Articles in the same Issue

https://doi.org/10.1515/jpem-2014-0122

Keywords for this article

alkaptonuria; Chinese; homogentisate 1,2-dioxygenase; mutation