Molecular genetics of PKU in Poland and potential impact of mutations on BH4 responsiveness.

Bik-Multanowski, Mirosław; Kałużny, Łukasz; Mozrzymas, Renata; Ołtarzewski, Mariusz; Starostecka, Ewa; Lange, Agata; Didycz, Bożena; Giżewska, Maria; Ulewicz-Filipowicz, J; Chrobot, Agnieszka; Mikołuć, Bożena; Szymczakiewicz-Multanowska, Agnieszka; Cichy, Wojciech; Pietrzyk, Jacek J

doi:10.18388/abp.2013_2029

Cited by 11 publications

(9 citation statements)

References 21 publications

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“…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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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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“…The method described provide a fast genotyping of patients with positive PKU newborn screening and it provides high-risk families with a rapid, accurate and cost-effective test for carrier screening. Although the test is based on Italian frequent mutations and the disease is characterized by very high allelic heterogeneity, the selected variants reach also a high detection rate in other populations, for example: 70.8% in Poland [22], 70.2% in Slovakia [23], 70% in southern Germany and 68% in western Germany [11], 76% in Denmark, 68% in Sweden [12], and 60% in Azerbaijan [24]. In Eastern Europe, there is a high prevalence of p.Arg408Trp mutation, for example, 48% of the alleles in Romania [12] and 63% in Poland [22], but in Bulgaria only two mutations, that are included in our panels, (c.1066-11G>A, p.Arg408Trp) reach 60% of the detection rate [12].…”

Section: Discussionmentioning

confidence: 99%

Molecular Analysis of PKU-Associated PAH Mutations: A Fast and Simple Genotyping Test

Tolve

Artiola

Pasquali

et al. 2018

MPs

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Neonatal screening for phenylketonuria (PKU, OMIM: 261600) was introduced at the end of the 1960s. We developed a rapid and simple molecular test for the most frequent phenylalanine hydroxylase (PAH, Gene ID: 5053) mutations. Using this method to detect the 18 most frequent mutations, it is possible to achieve a 75% detection rate in Italian population. The variants selected also reach a high detection rate in other populations, for example, 70% in southern Germany, 68% in western Germany, 76% in Denmark, 68% in Sweden, 63% in Poland, and 60% in Bulgaria. We successfully applied this confirmation test in neonatal screening for hyperphenylalaninemias using dried blood spots and obtained the genotype in approximately 48 h. The method was found to be suitable as second tier test in neonatal screening for hyperphenylalaninemias in neonates with a positive screening test. This test can also be useful for carrier screening because it can bypass the entire coding sequence and intron–exon boundaries sequencing, thereby overcoming the questions that this approach implies, such as new variant interpretations.

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“…U przedstawionej chorej występowała w układzie homozygotycznym najczęstsza w populacji polskiej mutacja (p.R408W) genu PAH, kodującego enzym hydroksylazę fenyloalaninową. 14 Wiek zajścia w obie ciąże przypadł na optymalny okres życia do podejmowania prokreacji 15,16 i nie występowało obciążenie nikotynizmem. Zgodnie z rekomendacjami dietę niskofenyloalaninową stosowano nie tylko w ciąży, ale i w okresie prekoncepcyjnym.…”

Section: Omówienieunclassified

Two singleton pregnancies of phenylketonuric woman (p.R408W/p.R408W) on low phenylalanine diet resulting in healthy offspring: A recurrent lack of expected meaningful increase in phenylalanine tolerance during the third trimester

Żółkowska¹,

Hozyasz²

2019

Piel. Zdr. Publ.

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Duże stężenia Phe w ciąży są przyczyną MPKU (upośledzenie umysłowe, małogłowie, wady wrodzone), któremu można zapobiec, stosując terapię dietą niskofenyloalaninową. Autorzy niniejszego artykułu przedstawili 2 ciąże pojedyncze (zakończone urodzeniem zdrowego potomstwa) pacjentki chorej na PKU, która pozostawała w stanie wyrównania metabolicznego zarówno w okresie prekoncepcyjnym, jak i będąc w ciąży. W praktyce klinicznej ocena tolerancji Phe opiera się na częstych oznaczeniach stężenia tego aminokwasu w powiązaniu z analizą jadłospisu. Zgodnie z danymi z piśmiennictwa autorzy oczekiwali znaczącego wzrostu tolerancji Phe w III trymestrze, gdyż jego brak uważa się za marker tej choroby także u płodu. Analizując wyniki badań pacjentki, zaobserwowano, że w pierwszej i drugiej ciąży tolerancja Phe w III trymestrze i podczas całej ciąży wzrosła odpowiednio o 453 mg (30,2%)/1653 mg (551%) i 200 mg (12,5%)/1560 mg (650%). Wzorzec zmian tolerancji Phe był podobny tylko w drugiej połowie obu ciąż. Niezbędne są dalsze badania nad czynnikami wpływającymi na homeostazę Phe w ciąży u chorych na fenyloketonurię. Słowa kluczowe: zdrowie publiczne, fenyloketonuria, tolerancja fenyloalaniny, oddziaływania matczyno-płodowe Cytowanie Żółkowska J, Hozyasz KK. Dwie ciąże pojedyncze u chorej na fenyloketonurię (p.R408W/p.R408W) na diecie niskofenyloalaninowej zakończone urodzeniem zdrowego potomstwa-powtarzalny brak oczekiwanego znaczącego wzrostu tolerancji fenyloalaniny w III trymestrze ciąży

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Molecular genetics of PKU in Poland and potential impact of mutations on BH4 responsiveness.

Cited by 11 publications

References 21 publications

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

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

Molecular Analysis of PKU-Associated PAH Mutations: A Fast and Simple Genotyping Test

Two singleton pregnancies of phenylketonuric woman (p.R408W/p.R408W) on low phenylalanine diet resulting in healthy offspring: A recurrent lack of expected meaningful increase in phenylalanine tolerance during the third trimester

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