Molecular analysis of PCCB gene in Korean patients with propionic acidemia

Kim, Soon Nam; Ryu, Kyung Hwa; Lee, Eun Ha; Kim, Jong Soo; Hahn, Si Houn

doi:10.1016/s1096-7192(02)00139-7

Cited by 17 publications

(5 citation statements)

References 24 publications

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“…In Japanese PCCA gene mutations were mainly 923-924insT, IVSl8-6C>G and R399Q, while PCCB gene mutations were mainly R410W, T428I and A153P ( 3 ). PCCB mutation in Korean population was mainly T428I, the gene mutation frequency of T428I mutation in PA children was as high as 56.3% ( 4 ). PA was common in Greenland Inuit people, and PCCB gene 1540insCCC mutation rate in the normal population was up to 5% ( 5 ).…”

Section: Discussionmentioning

confidence: 96%

A Novel PCCA Mutation in a Patient With Late-Onset Propionic Acidemia Identified by Genetic Diagnosis Panel

2018

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Background: Propionic acidemia (PA) is an extremely rare autosomal recessive disorder which is caused by the deficiency of propionyl-CoA carboxylase (PCC) and associated with pathogenic variants in PCCA or PCCB gene.Case Report: Detection of PA in neonates is possible using Propionyl carnitine (C3) analysis by tandem mass spectrometry (MS/MS) in dried blood spots (DBS). Here we report one patient with PA. C3 in this case was normal in the initial screening and recall check and only manifested as the slightly increase of C3/C2, 3-hydroxypropionate in urine was only slightly elevated. Then two pathogenic mutations (c.802C>T/c.827delG) were detected in the PCCA gene by Genetic diagnosis panel. Among them, the variation rs774738181 (c.802C>T) was present on the dbSNP database which appeared to be “Likely pathogenic” in GenBank dbSNP (100915068). c.827delG was a novel frameshift mutation, leading to p.Gly276ValfsX46 mutation of amino acid sequence in PCCA. The patient underwent 1 year of follow-up, had total of 7 times and remain asymptomatic whose blood ammonia and liver function were normal. When the child was 1 year of age (in May of 2017), C3 and 3-Hydroxypropionate sudden elevated significantly, that proved pathogenicity of c.802C>T and c.827delG.Conclusion: Two novel mutations (c. 802C>T and c.827delG) in PCCA gene may be associated with late-onset PA, expanding its mutational spectrum. Maybe there is relation between the severity of propionyl-CoA carboxylase (PCC) activity defects and different genotypes.

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Section: Discussionmentioning

confidence: 96%

A Novel PCCA Mutation in a Patient With Late-Onset Propionic Acidemia Identified by Genetic Diagnosis Panel

2018

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“…The most common Japanese PCCA gene mutations are 923_924insT, IVS18-6C>G, and R399Q, and the most common PCCB gene changes are R410W, T428I, and A153P [28] . Koreans are basically the PCCB gene T428I graph type, accounting for approximately 56.3% of Koreans [29] . However, no hotspot mutations in the PCCA or PCCB gene have been detected in Chinese patients.…”

Section: Molecular Geneticsmentioning

confidence: 99%

Late-onset propionic acidemia with epilepsy due to compound heterozygous variants in the PCCB gene: a case report and literature review

Shi,

Wei,

Gan

et al. 2024

Preprint

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Propionic acidemia is an autosomal recessively inherited metabolic disorder attributed to a mutation in the PCCA or PCCB gene resulting in a lack of propionyl coenzyme A carboxylase, which permits an abnormal accumulation of propionate and its metabolite precursors in the body. The clinical presentation and severity of propionic acidemia vary widely among patients, and late-onset propionic acidemia might manifest at any stage of life, including infancy, childhood, or even later. In this paper, a case of late-onset propionic acidemia with epilepsy caused by compound heterozygous variations of the PCCB gene was reported. The pathogenic gene, accessory examination, diagnosis, treatment, etc., were investigated, and related written works were reviewed to advance clinicians' understanding of the findings and treatment of the illness.

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“…In this study, 78 pregnancies (58 families) in which the probands diagnosed with PA were referred to our center Tables 1 and 2 and Table S2 [16][17][18][19][20][21][22][23]. Written informed consent was obtained from all participants, and our study was approved by the Ethics Committee of Xinhua Hospital.…”

Section: Families and Probandsmentioning

confidence: 99%

Biochemical and genetic approaches to the prenatal diagnosis of propionic acidemia in 78 pregnancies

Dai

Xiao

Zhang

et al. 2020

Orphanet J Rare Dis

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Background Propionic acidemia (PA) is a serious metabolic disorder, and different approaches have been applied to its prenatal diagnosis. To evaluate the reliability and validity of a biochemical strategy in the prenatal diagnosis of PA, we conducted a retrospective study of our 11-year experiences at a single center. Methods We accumulated data from 78 pregnancies from 58 families referred to our center and provided prenatal diagnosis by directed genetic analysis and/or metabolite measurement using tandem mass spectrometry (MS/MS) and gas chromatography/mass spectrometry (GC/MS) of amniotic fluid (AF) samples. Results Sixty-five unaffected fetuses (83.33%) and 13 affected fetuses (16.67%) were confirmed in our study. The characteristic metabolites including propionylcarnitine (C3) level, C3/acetylcarnitine (C2) ratio and 2-methylcitric acid (2MCA) level in unaffected and affected groups showed significant differences (P < 0.0001), while the level of 3-hydroxypropionic acid (3HPA) showed no significant difference between the two groups (P > 0.05).Of the 78 pregnancies, 24 fetuses were found to have either one causative pathogenic variant or were without genetic information in the proband. Three of these fetuses had elevated AF levels of C3, C3/C2 ratio, and 2MCA and, thus, were determined to be affected, while the remaining fetuses were determined to be unaffected based on a normal AF metabolite profile. Our genetic and biochemical results were highly consistent with postnatal follow-up results on all unaffected fetuses. Conclusions We conclude that a biochemical approach can serve as a fast and convenient prenatal diagnostic method for pregnancies at an increased risk for PA, which could be used in conjunction with genetic testing for precise prenatal diagnosis of this disorder. In our analysis, the characteristic metabolites C3 level, C3/C2 ratio, and 2MCA level in AF supernatant were dependable biochemical markers for diagnosis, of which the C3/C2 ratio appears to be the most reliable biochemical marker for the prenatal diagnosis of PA.

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Molecular analysis of PCCB gene in Korean patients with propionic acidemia

Cited by 17 publications

References 24 publications

A Novel PCCA Mutation in a Patient With Late-Onset Propionic Acidemia Identified by Genetic Diagnosis Panel

A Novel PCCA Mutation in a Patient With Late-Onset Propionic Acidemia Identified by Genetic Diagnosis Panel

Late-onset propionic acidemia with epilepsy due to compound heterozygous variants in the PCCB gene: a case report and literature review

Biochemical and genetic approaches to the prenatal diagnosis of propionic acidemia in 78 pregnancies

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