The spectrum of mutations in the PAH gene in patients with hyperphenylalaninemia from the Karachay-Cherkess Republic

Гундорова, П.; Зинченко, Р. А.; Makaov, A. Kh.; Polyakov, A. V.

doi:10.1134/s1022795417070043

Cited by 7 publications

(6 citation statements)

References 22 publications

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“…Newborn screening data show the incidence of HPA in the KCR as 1:850 newborns [ 8 ]. To calculate the PKU incidence in different ethnic groups, we performed DNA analysis among healthy residents.…”

Section: Resultsmentioning

confidence: 99%

“…Interestingly, the p.Arg261* (c.781C>T) PAH variant is very widespread among them. The allele frequency of p.Arg261* is 68.4% among PKU patients and 32.5% among mHPA patients [ 8 , 9 ], so it is the predominant variant in this region. The presence of those genetic peculiarities in Karachay-Cherkessia presumably results from reproductive isolation and genetic drift in populations residing on this territory.…”

Section: Introductionmentioning

confidence: 99%

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Molecular-genetic causes for the high frequency of phenylketonuria in the population from the North Caucasus

et al. 2018

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Phenylketonuria is an inherited disease caused by mutations in the phenylalanine hydroxylase gene PAH. Different PAH pathogenic variants occur in different ethnic groups with various frequencies and the incidence of the disease itself varies from country to country. In the Caucasus region of Russia, some ethnoses are geographically and culturally isolated from each other. The tradition of monoethnic marriages may cause decreased genetic variability in those populations. In the Karachay-Cherkess Republic (Russia), the highest incidence of phenylketonuria in the world has been detected (1:850 newborns) in the region and 1:332 among the titular nation Karachays. Here, we showed that this phenomenon is due to the widespread prevalence of the p.Arg261* variant. Its allele frequency among Karachay patients with PKU was 68.4% and the carrier frequency in Karachays was 1:16 healthy individuals. PAH haplotype analysis showed a unique common origin. The founder haplotype and mutation “age” were estimated by analyzing the linkage disequilibrium between p.Arg261* and extragenic short tandem repeat loci. The p.Arg261* variant occurred in the Karachays population 10.2 ± 2.7 generations ago (275 ± 73 years) and its spread occurred in parallel with the growth of the population.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Molecular-genetic causes for the high frequency of phenylketonuria in the population from the North Caucasus

et al. 2018

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“…Numerous studies have shown that the frequencies of Mendelian diseases and different pathogenic variants can vary significantly among different regions of Russia [35][36][37][38][39][40][41][42]. Although Russians are the major ethnic group in Russia (111 million out of the total population of 146 million), there is a significant number of indigenous ethnic populations living for hundreds of years in their historical locations (over 200 different ethnicities and ethnic groups, according to the 2010 Census) unevenly dispersed across the vast territory of Russia [34].…”

Section: Discussionmentioning

confidence: 99%

A new approach to estimating the prevalence of hereditary hearing loss: An analysis of the distribution of sign language users based on census data in Russia

et al. 2020

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The absence of comparable epidemiological data challenges the correct estimation of the prevalence of congenital hearing loss (HL) around the world. Sign language (SL) is known as the main type of communication of deaf people. We suggest that the distribution of SL can be interpreted as an indirect indicator of the prevalence of congenital HL. Since a significant part of congenital HL is due to genetic causes, an assessment of the distribution of SL users can reveal regions with an extensive accumulation of hereditary HL. For the first time, we analyzed the data on the distribution of SL users that became available for the total population of Russia by the 2010 census. Seventy-three out of 85 federal regions of Russia were ranked into three groups by the 25th and 75th percentiles of the proportion of SL users: 14 regions—“low proportion”; 48 regions—“average proportion”; and 11 regions—“high proportion”. We consider that the observed uneven prevalence of SL users can reflect underlying hereditary forms of congenital HL accumulated in certain populations by specific genetic background and population structure. At least, the data from this study indicate that the highest proportions of SL users detected in some Siberian regions are consistent with the reported accumulation of specific hereditary HL forms in indigenous Yakut, Tuvinian and Altaian populations.

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“…Hyperphenylalaninemia (HPA) is the result of increased levels of Phe in the blood. This level is less than 2 mg/dL in healthy children, 2-10 in HPA patients, 10-15 in mild PKU, 15-20 in moderate PKU, and more than 20 mg/dL in classic PKU (3). In addition, 98% of all cases of HPA are related to mutations in the PAH gene (4).…”

Section: Introductionmentioning

confidence: 94%

Detection of IVS4+1G>A mutation in phenylalanine hydroxylase gene in North of Iran using PCR-sequencing

Chelak

Koohpar

2023

J Shahrekord Univ Med Sci

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Background and aims: Phenylketonuria (PKU) is an autosomal recessive disorder of phenylalanine (Phe) metabolism. Mutations in the phenylalanine hydroxylase (PAH) gene are the main reason for the incidence of PKU. To date, more than 1180 variants have been detected in the PAH gene. Given that the distribution pattern of mutations in the PAH gene is specific to each population, the present study was conducted to detect exon 4 mutations and adjacent flanking regions of the PAH gene in northern Iran. Methods: This is a descriptive cross-sectional study, in which 24 unrelated PKU patients in Taleghani Hospital in Gorgan were enrolled for a one-year period. After extraction of genomic DNA from leukocytes, identification of exon 4 mutations and adjacent flanking regions was performed using polymerase chain reaction (PCR) and sequencing techniques. Results: In this study, IVS4+1G>A mutation was detected in one allele (2.08%) among 48 alleles. Moreover, IVS4+47C>T and IVS3-22C>T polymorphisms were observed in 12 alleles (25%) and eight alleles (16.7%), respectively. Conclusion: In the present study, IVS4+1G>A mutation was only found in 2% of chromosomes. Hence, different mutations are responsible for PKU disease in the north of Iran, and further studies are recommended to identify all mutations in the PAH gene in the region.

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The spectrum of mutations in the PAH gene in patients with hyperphenylalaninemia from the Karachay-Cherkess Republic

Cited by 7 publications

References 22 publications

Molecular-genetic causes for the high frequency of phenylketonuria in the population from the North Caucasus

Molecular-genetic causes for the high frequency of phenylketonuria in the population from the North Caucasus

A new approach to estimating the prevalence of hereditary hearing loss: An analysis of the distribution of sign language users based on census data in Russia

Detection of IVS4+1G>A mutation in phenylalanine hydroxylase gene in North of Iran using PCR-sequencing

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