Spectrum of PAH gene variants among a population of Han Chinese patients with phenylketonuria from northern China
Abstract Background Phenylketonuria (PKU), which primarily results from a deficiency of phenylalanine hydroxylase (PAH), is one of the most common inherited inborn errors of metabolism that impairs postnatal cognitive development. The incidence of various PAH variations differs by race and ethnicity...
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BMC
2017-10-01
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| Series: | BMC Medical Genetics |
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| Online Access: | http://link.springer.com/article/10.1186/s12881-017-0467-7 |
| _version_ | 1819276762400423936 |
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| author | Ning Liu Qiuying Huang Qingge Li Dehua Zhao Xiaole Li Lixia Cui Ying Bai Yin Feng Xiangdong Kong |
| author_facet | Ning Liu Qiuying Huang Qingge Li Dehua Zhao Xiaole Li Lixia Cui Ying Bai Yin Feng Xiangdong Kong |
| author_sort | Ning Liu |
| collection | DOAJ |
| description | Abstract Background Phenylketonuria (PKU), which primarily results from a deficiency of phenylalanine hydroxylase (PAH), is one of the most common inherited inborn errors of metabolism that impairs postnatal cognitive development. The incidence of various PAH variations differs by race and ethnicity. The aim of the present study was to characterize the PAH gene variants of a Han population from Northern China. Methods In total, 655 PKU patients and their families were recruited for this study; each proband was diagnosed both clinically and biochemically with phenylketonuria. Subjects were sequentially screened for single-base variants and exon deletions or duplications within PAH via direct Sanger sequencing and multiplex ligation-dependent probe amplification (MLPA). Results A spectrum of 174 distinct PAH variants was identified: 152 previously documented variants and 22 novel variants. While single-base variants were distributed throughout the 13 exons, they were particularly concentrated in exons 7 (33.3%), 11 (14.2%), 6 (13.2%), 12 (11.0%), 3 (10.4%), and 5 (4.4%). The predominant variant was p.Arg243Gln (17.7%), followed by Ex6-96A > G (8.3%), p.Val399 = (6.4%), p.Arg53His (4.7%), p.Tyr356* (4.7%), p.Arg241Cys (4.6%), p.Arg413Pro (4.6%), p.Arg111* (4.4%), and c.442-1G > A (3.4%). Notably, two patients were also identified as carrying de novo variants. Conclusion The composition of PAH gene variants in this Han population from Northern China was distinct from those of other ethnic groups. As such, the construction of a PAH gene variant database for Northern China is necessary to lay a foundation for genetic-based diagnoses, prenatal diagnoses, and population screening. |
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| institution | Directory Open Access Journal |
| issn | 1471-2350 |
| language | English |
| last_indexed | 2024-12-23T23:45:22Z |
| publishDate | 2017-10-01 |
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| record_format | Article |
| series | BMC Medical Genetics |
| spelling | doaj.art-c5db2aea75dd434aa902b855bbcd60fb2022-12-21T17:25:31ZengBMCBMC Medical Genetics1471-23502017-10-011811710.1186/s12881-017-0467-7Spectrum of PAH gene variants among a population of Han Chinese patients with phenylketonuria from northern ChinaNing Liu0Qiuying Huang1Qingge Li2Dehua Zhao3Xiaole Li4Lixia Cui5Ying Bai6Yin Feng7Xiangdong Kong8Genetics and Prenatal Diagnosis Center, The First Affiliated Hospital of Zhengzhou University, Henan Engineering Research Center for Gene Editing of Human Genetic DiseaseState Key Laboratory of Cellular Stress Biology, State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, Engineering Research Centre of Molecular Diagnostics, Ministry of Education, School of Life Sciences, Xiamen UniversityState Key Laboratory of Cellular Stress Biology, State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, Engineering Research Centre of Molecular Diagnostics, Ministry of Education, School of Life Sciences, Xiamen UniversityNeonatal Screening Center, The Third Affiliated Hospital of Zhengzhou UniversityNeonatal Screening Center, The Third Affiliated Hospital of Zhengzhou UniversityNeonatal Screening Center, Zhengzhou Maternity and Child Care HospitalGenetics and Prenatal Diagnosis Center, The First Affiliated Hospital of Zhengzhou University, Henan Engineering Research Center for Gene Editing of Human Genetic DiseaseGenetics and Prenatal Diagnosis Center, The First Affiliated Hospital of Zhengzhou University, Henan Engineering Research Center for Gene Editing of Human Genetic DiseaseGenetics and Prenatal Diagnosis Center, The First Affiliated Hospital of Zhengzhou University, Henan Engineering Research Center for Gene Editing of Human Genetic DiseaseAbstract Background Phenylketonuria (PKU), which primarily results from a deficiency of phenylalanine hydroxylase (PAH), is one of the most common inherited inborn errors of metabolism that impairs postnatal cognitive development. The incidence of various PAH variations differs by race and ethnicity. The aim of the present study was to characterize the PAH gene variants of a Han population from Northern China. Methods In total, 655 PKU patients and their families were recruited for this study; each proband was diagnosed both clinically and biochemically with phenylketonuria. Subjects were sequentially screened for single-base variants and exon deletions or duplications within PAH via direct Sanger sequencing and multiplex ligation-dependent probe amplification (MLPA). Results A spectrum of 174 distinct PAH variants was identified: 152 previously documented variants and 22 novel variants. While single-base variants were distributed throughout the 13 exons, they were particularly concentrated in exons 7 (33.3%), 11 (14.2%), 6 (13.2%), 12 (11.0%), 3 (10.4%), and 5 (4.4%). The predominant variant was p.Arg243Gln (17.7%), followed by Ex6-96A > G (8.3%), p.Val399 = (6.4%), p.Arg53His (4.7%), p.Tyr356* (4.7%), p.Arg241Cys (4.6%), p.Arg413Pro (4.6%), p.Arg111* (4.4%), and c.442-1G > A (3.4%). Notably, two patients were also identified as carrying de novo variants. Conclusion The composition of PAH gene variants in this Han population from Northern China was distinct from those of other ethnic groups. As such, the construction of a PAH gene variant database for Northern China is necessary to lay a foundation for genetic-based diagnoses, prenatal diagnoses, and population screening.http://link.springer.com/article/10.1186/s12881-017-0467-7PhenylketonuriaPhenylalanine hydroxylase genePAH gene variantMLPA |
| spellingShingle | Ning Liu Qiuying Huang Qingge Li Dehua Zhao Xiaole Li Lixia Cui Ying Bai Yin Feng Xiangdong Kong Spectrum of PAH gene variants among a population of Han Chinese patients with phenylketonuria from northern China BMC Medical Genetics Phenylketonuria Phenylalanine hydroxylase gene PAH gene variant MLPA |
| title | Spectrum of PAH gene variants among a population of Han Chinese patients with phenylketonuria from northern China |
| title_full | Spectrum of PAH gene variants among a population of Han Chinese patients with phenylketonuria from northern China |
| title_fullStr | Spectrum of PAH gene variants among a population of Han Chinese patients with phenylketonuria from northern China |
| title_full_unstemmed | Spectrum of PAH gene variants among a population of Han Chinese patients with phenylketonuria from northern China |
| title_short | Spectrum of PAH gene variants among a population of Han Chinese patients with phenylketonuria from northern China |
| title_sort | spectrum of pah gene variants among a population of han chinese patients with phenylketonuria from northern china |
| topic | Phenylketonuria Phenylalanine hydroxylase gene PAH gene variant MLPA |
| url | http://link.springer.com/article/10.1186/s12881-017-0467-7 |
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