Identification of three novel mutations in Korean phenylketonuria patients: R53H, N207D, and Y325X

Park, Young Shik; Seoung, Chang Soo; Lee, Soo Woong; Oh, Keun Hee; Lee, Dong Hwan; Yim, Jeongbin

doi:10.1002/humu.1380110140

Cited by 10 publications

(5 citation statements)

References 8 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Y356X is a null mutation and may not be the BH 4 -responsive allele. R408Q was Table 2 Spectrum of PAH mutations detected in this study a (1) Mutations reported in the PAHdb, (2) mutation reported by Song et al (2003), (3) mutation reported by Chien et al (2004), (4) mutation reported by Park et al (1998) reported to be associated with near-normal levels of residual activity in eukaryotic and prokaryotic expression system (Pey et al 2003). The residual activity of R408Q and the BH 4 responsiveness of patient 3 indicate that R408Q is one of the BH 4 -responsive alleles.…”

Section: Resultsmentioning

confidence: 84%

The molecular basis of phenylketonuria in Koreans

et al. 2004

Self Cite

View full text Add to dashboard Cite

Phenylketonuria (PKU) is an inborn error of metabolism that results from a deficiency of phenylalanine hydroxylase (PAH). We characterized the PAH mutations of 79 independent Korean patients with PKU or hyperphenylalaninemia. PAH nucleotide sequence analysis revealed 39 different mutations, including ten novel mutations. The novel mutations consisted of nine missense mutations (P69S, G103S, N207D, T278S, P281A, L293M, G332V, S391I, and A447P) and a novel splice site variant (IVS10À3C>G). R243Q, IVS4À1G>A, and E6À96A>G were the most prevalent mutations, as they accounted for 32% of the total mutant alleles in this study. Although some common characteristics of allele frequency and distribution were identified among oriental populations, several distinctive characteristics were revealed in Korean patients. Although the R413P allele is the most prevalent form (30.5%) in Japanese, we detected it in only five chromosomes from 158 independent chromosomes (3.2%). The A259T allele, which has not yet been found in oriental populations, was frequently found in this study. We also observed that tetrahydrobiopterin (BH 4 ) responsiveness was associated with specific genotypes (R53H, R241C, and R408Q), suggesting there are some correlations between phenotype and genotype.

show abstract

Section: Resultsmentioning

confidence: 84%

The molecular basis of phenylketonuria in Koreans

et al. 2004

Self Cite

View full text Add to dashboard Cite

show abstract

“…According to the integrative Japanese Genome Variation Database (iJGVD, , accessed on 18 February 2021), the allele frequency of p.R53H in the general Japanese population was reported to be as high as 5% [ 6 ]. Several studies have reported that p.R53H is associated with HPA phenotype [ 3 , 4 , 7 , 8 , 9 ].On the contrary, a few reports exist that correlates PKU with p.R53H [ 9 , 10 ].…”

Section: Introductionmentioning

confidence: 99%

Clinical and Genetic Characteristics of Patients with Mild Hyperphenylalaninemia Identified by Newborn Screening Program in Japan

Odagiri

Kabata

Tomita

et al. 2021

IJNS

View full text Add to dashboard Cite

Phenylketonuria (PKU) and hyperphenylalaninemia (HPA), both identified in newborn screening, are attributable to variants in PAH. Reportedly, the p.R53H(c.158G>A) variant is common in patients with HPA in East Asia. Here, we aimed to define the association between p.R53H and HPA phenotype, and study the long-term outcome of patients with HPA carrying p.R53H. We retrospectively reviewed the genotype in 370 patients detected by newborn screening, and identified the phenotype in 280 (117, HPA; 163, PKU). p.R413P(c.1238G>C) was the most frequently found (n = 117, 31.6%) variant, followed by p.R53H (n = 89, 24.1%). The odds ratio for heterozygous p.R53H to cause HPA was 48.3 (95% CI 19.410–120.004). Furthermore, we assessed the non-linear association between the phenylalanine (Phe) value and elapsed time using the follow-up data of the blood Phe levels of 73 patients with HPA carrying p.R53H. The predicted levels peaked at 161.9 μmol (95% CI 152.088–172.343) at 50–60 months of age and did not exceed 360 μmol/L during the 210-month long observation period. The findings suggest that patients with HPA, carrying p.R53H, do not need frequent Phe monitoring as against those with PKU. Our study provides convincing evidence to determine clinical management of patients detected through newborn screening in Japan.

show abstract

“…The volunteer couple in this study underwent single-gene carrier screening before pregnancy. The screening result showed that the wife carried one pathogenic mutation, i.e., c.109G>A of GJB2 gene ( Abe et al, 2000 ), and the husband carried four disease-associated mutations, i.e., GJB2 c.235del ( Fuse et al, 1999 ), DYSF c.4585C>T ( Guglieri et al, 2008 ), SLC26A4 c.2236-25T>A ( Yuan et al, 2012 ), and PAH c.158G>A ( Park et al, 1998 ). Detailed information is shown in Table 1 .…”

Section: Methodsmentioning

confidence: 99%

“…i.e., GJB2 c.235del (Fuse et al, 1999), DYSF c.4585C>T (Guglieri et al, 2008), SLC26A4 c.2236-25T>A (Yuan et al, 2012), and PAH c.158G>A (Park et al, 1998). Detailed information is shown in Table 1.…”

Section: Clinical Information On the Involved Couple And Target Mutat...mentioning

confidence: 99%

Applying amplification refractory mutation system technique to detecting cell-free fetal DNA for single-gene disorders purpose

Jian

Zhang

et al. 2023

Front. Genet.

View full text Add to dashboard Cite

Non-invasive prenatal diagnosis for single-gene disorders (NIPD) is still in development and deserves further study. The advent of next-generation sequencing technology significantly improved the detection of multiple mutations for non-invasive prenatal diagnosis for single-gene disorder purposes. However, bespoke amplicon-based NGS assays are costly. In this study, we developed a new strategy for non-invasive prenatal screening for single-gene disorders based on a capillary electrophoresis (CE) platform using an amplification refractory mutation system (ARMS)-PCR technique. Allele-specific primers for several disease-correlated mutations were designed, and subsequently, sensitivity and specificity assays were conducted. Assays on simulated two-person DNA mixtures showed that three primers targeting the mutant allele could detect minor DNA components in 1:500 mixtures. All primers showed positive results at 0.01 ng of the template DNA. Cell-free fetal DNA was extracted from a pregnant woman’s peripheral blood for the detection of paternally inherited mutations. Our results showed that one primer successfully amplified the mutant allele of fetal DNA in maternal plasma, which was confirmed by genotyping the genomic DNA extracted from amniotic fluid. This study suggested that the ARMS-PCR technique, a fast and cost-effective method, might be a promising method used to target de novo or paternally inherited pathogenic mutations in maternal plasma.

show abstract

Identification of three novel mutations in Korean phenylketonuria patients: R53H, N207D, and Y325X

Cited by 10 publications

References 8 publications

The molecular basis of phenylketonuria in Koreans

The molecular basis of phenylketonuria in Koreans

Clinical and Genetic Characteristics of Patients with Mild Hyperphenylalaninemia Identified by Newborn Screening Program in Japan

Applying amplification refractory mutation system technique to detecting cell-free fetal DNA for single-gene disorders purpose

Contact Info

Product

Resources

About