Mutation spectrum of phenylketonuria in Syrian population: Genotype–phenotype correlation

Murad, Hossam; Dabboul, Amir; Moassas, Faten; Alasmar, Diana; Al‐Achkar, Walid

doi:10.1016/j.gene.2013.07.001

Cited by 13 publications

(12 citation statements)

References 29 publications

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“…In this study, 61 PAH mutations were detected using NGS method from 35 children with PAH deficient PKU. The detection rate was about 87.14% and the results were comparable to those of Zhu [9], Murad [18], and Polak [19]. PAH was consisted of 13 exons and 12 introns.…”

Section: Discussionsupporting

confidence: 77%

PAH mutation spectrum and correlation with PKU manifestation in north Jiangsu province population

Wang

Jiang

Baocheng

2017

The Kaohsiung J of Med Scie

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Phenylketonuria (PKU) is a common autosomal recessive disorder of phenylalanine metabolism and mainly results a deficiency of phenylalanine hydroxylase gene (PAH). The incidence of various PAH mutations have race and ethnicity differences. We report a spectrum of PAH mutations complied from 35 PKU children who are all Chinese Han population from north Jiangsu in this study. All 13 exons and their flanking intron sequences of PAH were determined by Ion Torrent PGM™ sequencing. The relationship of genotype and phenotype was analyzed based on the sum of the arbitrary value (AV) values of the two alleles. We identified 61 mutations, with a frequency of 87.14%, among 70 alleles of 35 patients. The most prevalent mutations were R243Q (26.23%), R241C (9.84%) and V399V (8.20%). Furthermore, the consistency between prediction of the biochemical phenotype and the observed phenotype was 81.25%, with the highest consistency observed in classic PKU (87.50%). A significant correlation was found between pretreatment levels of phenylalanine and AV sum (r = -0.87, P < 0.05). Finally, our study constructs PAH mutation spectrum by next generation sequencing (NGS), and reveals that the PAH genotypes and biochemical phenotypes were significantly correlated. These offers facilitate the provision of appropriate genetic counseling for PKU patients.

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Section: Discussionsupporting

confidence: 77%

PAH mutation spectrum and correlation with PKU manifestation in north Jiangsu province population

Wang

Jiang

Baocheng

2017

The Kaohsiung J of Med Scie

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“…A comprehensive survey of the mutation spectrum of the protein of interest in a given population not only can provide insight into the structural and functional aspects of the protein as well as genotype-phenotype correlations 14 15 20 22 23 26 28 42 , but also facilitate genetic counseling in patients’ families. In this study, we described the molecular basis of PKU in a mainland Chinese population by analysing mutations in the PAH gene using NGS.…”

Section: Discussionmentioning

confidence: 99%

“…The frequencies and distributions of PAH mutations also differs among different populations 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 . The wide variability of common mutations between ethnic groups and geographical areas makes PAH deficiency a genetic disease of great allelic heterogeneity.…”

mentioning

confidence: 99%

Molecular characterisation of phenylketonuria in a Chinese mainland population using next-generation sequencing

Jia

Liu

et al. 2015

Sci Rep

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Phenylketonuria (PKU) is an inherited autosomal recessive disorder of phenylalanine metabolism, mainly caused by a deficiency of phenylalanine hydroxylase (PAH). The incidence of various PAH mutations differs among race and ethnicity. Here we report a spectrum of PAH mutations complied from 796 PKU patients from mainland China. The all 13 exons and adjacent intronic regions of the PAH gene were determined by next-generation sequencing. We identified 194 different mutations, of which 41 are not reported before. Several mutations reoccurred with high frequency including p.R243Q, p.EX6-96A > G, p.V399V, p.R241C, p.R111*, p.Y356*, p.R413P, and IVS4-1G > A. 76.33% of mutations were localized in exons 3, 6, 7, 11, 12. We further compared the frequency of each mutation between populations in northern and southern China, and found significant differences in 19 mutations. Furthermore, we identified 101 mutations that are not reported before in Chinese population, our study thus broadens the mutational spectrum of Chinese PKU patients. Additionally, 41 novel mutations will expand and improve PAH mutation database. Finally, our study offers proof that NGS is effective, reduces screening times and costs, and facilitates the provision of appropriate genetic counseling for PKU patients.

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“…Tunisia, Lebanon, Syria), which have not introduced the newborn screening for PKU. These reports clearly show that PKU is one of the most common preventable causes of mental retardation [10][11][12]. Furthermore, the introduction of the newborn screening for PKU is a cost-effective practice also in a developing country [13].…”

Section: Phenylketonuria Newborn Screening In Developing Countriesmentioning

confidence: 94%

Fifty years of phenylketonuria newborn screening — A great success for many, but what about the rest?

Grošelj

Tanšek

Battelino

2014

Molecular Genetics and Metabolism

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Mutation spectrum of phenylketonuria in Syrian population: Genotype–phenotype correlation

Cited by 13 publications

References 29 publications

PAH mutation spectrum and correlation with PKU manifestation in north Jiangsu province population

PAH mutation spectrum and correlation with PKU manifestation in north Jiangsu province population

Molecular characterisation of phenylketonuria in a Chinese mainland population using next-generation sequencing

Fifty years of phenylketonuria newborn screening — A great success for many, but what about the rest?

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