Abstract
Purpose
The purpose of the study was to investigate mutations of the UPB1 gene in two Chinese families with β-ureidopropionase deficiency and the heterozygous carrier frequency in Chinese.
Methods
Genomic DNA was extracted from peripheral blood leukocytes from all available family members and 500 unrelated healthy controls. Then, all exons and flanking intron regions of the UPB1 gene were amplified by PCR and analyzed by direct sequencing in two patient-families. Finally, the carrier frequency of the c.977G>A (p.R326Q) mutation was identified by PCR restriction fragment length polymorphism in 500 healthy controls.
Results
The two patients had the same homozygous missense mutation in exon 9 (c.977G>A; p.R326Q), and the carrier frequency of this mutation was 2.8 % in the Northern Chinese population, which suggests that about 1:5,102 Chinese are expected to suffer from UPB1 deficiency.
Conclusions
The c.977G>A (p.R326Q) is the most common mutation of the UPB1 gene in Chinese. The predicted incidence indicates that β-ureidopropionase deficiency is significantly underdiagnosed in the Chinese population. It should be necessary to add β-ureidopropionase deficiency to high-risk screening for the symptomatic patients group.
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Abbreviations
- GC/MS:
-
Gas chromatograph/mass spectrometer
- ACRS:
-
Amplication created restriction site
- RFLP:
-
Restriction fragment length polymorphism
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Acknowledgments
The authors express their gratitude to all the patients and their families for participating in this genetic study.
Authors’ contributions
Jianbo Shu designed the study, analyzed genetic data, interpreted the results, and wrote the draft of the paper. Xiqian Lv was involved in the designing of the study, the genetic analysis of the UPB1 gene, and the writing of the manuscript. Shuzhen Jiang was involved in designing the PFLP assay, the analysis of mutations, and was involved in the writing of the manuscript. Yuqin Zhang and Aiming Situ provided clinical diagnosis and genetic counseling. Chunhua Zhang performed GC/MS detection. Yingtao Meng participated in performing the PFLP assay. Haiquan Xu was involved in recruitment of patients and collection of blood samples. Li Song participated in the experimental design, interpretation of the results, and supervision of the project, obtained funding, and critically revised the figures, tables, and entire manuscript. All authors read and approved the final manuscript.
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The author(s) declare that they have no competing interests.
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Jianbo Shu and Xiqian Lv are equal contributors.
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Shu, J., Lv, X., Jiang, S. et al. Genetic analysis of the UPB1 gene in two new Chinese families with β-ureidopropionase deficiency and the carrier frequency of the mutation c.977G>A in Northern China. Childs Nerv Syst 30, 2109–2114 (2014). https://doi.org/10.1007/s00381-014-2541-1
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DOI: https://doi.org/10.1007/s00381-014-2541-1