Dataset Information

Identification of deep intronic variants of PAH in phenylketonuria using full-length gene sequencing.

ABSTRACT:

Background

Phenylketonuria (PKU) is an autosomal recessive congenital metabolic disorder caused by PAH variants. Previously, approximately 5% of PKU patients remained undiagnosed after Sanger sequencing and multiplex ligation-dependent probe amplification. To date, increasing numbers of pathogenic deep intronic variants have been reported in more than 100 disease-associated genes.

Methods

In this study, we performed full-length sequencing of PAH to investigate the deep intronic variants in PAH of PKU patients without definite genetic diagnosis.

Results

We identified five deep intronic variants (c.1199+502A>T, c.1065+241C>A, c.706+368T>C, c.706+531>C, and c.706+608A>C). Of these, the c.1199+502A>T variant was found at high frequency and may be a hotspot PAH variant in Chinese PKU. c.706+531T>C and c.706+608A>C are two novel variants that extend the deep intronic variant spectrum of PAH.

Conclusion

Deep intronic variant pathogenicity analysis can further improve the genetic diagnosis of PKU patients. In silico prediction and minigene analysis are powerful approaches for studying the functions and effects of deep intronic variants. Targeted sequencing after full-length gene amplification is an economical and effective tool for the detection of deep intron variation in genes with small fragments.

SUBMITTER: Zhang C

PROVIDER: S-EPMC10214626 | biostudies-literature | 2023 May

REPOSITORIES: biostudies-literature

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Publications

Identification of deep intronic variants of PAH in phenylketonuria using full-length gene sequencing.

Zhang Chuan C Yan Yousheng Y Zhou Bingbo B Wang Yupei Y Tian Xinyuan X Hao Shengju S Ma Panpan P Zheng Lei L Zhang Qinghua Q Hui Ling L Wang Yan Y Cao Zongfu Z Ma Xu X

Orphanet journal of rare diseases 20230526 1

<h4>Background</h4>Phenylketonuria (PKU) is an autosomal recessive congenital metabolic disorder caused by PAH variants. Previously, approximately 5% of PKU patients remained undiagnosed after Sanger sequencing and multiplex ligation-dependent probe amplification. To date, increasing numbers of pathogenic deep intronic variants have been reported in more than 100 disease-associated genes.<h4>Methods</h4>In this study, we performed full-length sequencing of PAH to investigate the deep intronic va ...[more]

PMID: 37237386

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Dataset Information

Identification of deep intronic variants of PAH in phenylketonuria using full-length gene sequencing.

Background

Methods

Results

Conclusion

Publications

Identification of deep intronic variants of PAH in phenylketonuria using full-length gene sequencing.

Similar Datasets

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