Genotype-phenotype analysis of von Hippel-Lindau syndrome in Korean families: HIF-α binding site missense mutations elevate age-specific risk for CNS hemangioblastoma.

Background: von Hippel-Lindau (VHL) disease is a rare hereditary tumor syndrome caused by VHL gene mutations that is characterized by heterogeneous phenotypes such as benign/malignant tumors of the central nervous system, retina, kidney, adrenal gland, and pancreas. The genotype-phenotype correlation has not been well characterized in the Korean population so far. Therefore, this study aimed to evaluate the VHL mutation spectrum and genotype-phenotype correlations in Korean VHL patients.

Performance of two commercially available BCR-ABL1 quantification assays that use an international reporting scale.

Background: Quantifying the BCR-ABL1 rearrangement is important for monitoring chronic myelogenous leukemia (CML). To standardize BCR-ABL1 quantification, the World Health Organization (WHO) established the first international genetic reference panel. Here, we compared the BCR-ABL1 levels determined using international scale (IS)-based commercially available assays.

Diagnostic application of an extensive gene panel for Leber congenital amaurosis with severe genetic heterogeneity.

Leber congenital amaurosis (LCA) is a genetically heterogeneous disorder and the most severe form of inherited retinal dystrophy. We report results of a diagnostic application of an extensive gene panel composed of 204 retinal dystrophy-related genes and discuss its feasibility as a diagnostic tool. Nineteen unrelated LCA patients were included in the study: two patients for validation purposes of our gene panel, 15 previously analyzed patients with no identified mutations, and two previously unanalyzed patients.

Identification of two novel NPM1 mutations in patients with acute myeloid leukemia.

Background: Genetic abnormalities in adult AML are caused most frequently by somatic mutations in exon 12 of the NPM1 gene, which is observed in approximately 35% of AML patients and up to 60% of patients with cytogenetically normal AML (CN-AML).

Methods: We performed mutational analysis, including fragment analysis and direct sequencing of exon 12 of the NPM1 gene, on 83 AML patients to characterize the NPM1 mutations completely.

Results: In this study, NPM1 mutations were identified in 19 (22.

Evaluation of two hepatitis C virus genotyping assays based on the 5' untranslated region (UTR): the limitations of 5' UTR-based assays and the need for a supplementary sequencing-based approach.

We evaluated two genotyping methodologies that characterize the 5' untranslated region (5' UTR) of the hepatitis C virus (HCV) genome. The limitations of these genotype assays need to be thoroughly evaluated, and sequencing-based approaches may be needed to complement these methods in clinical settings.

Detection of very large off-ladder alleles at the PentaE locus in a 15 locus autosomal STR database of 199 Korean individuals.

Short tandem repeat (STR) loci in human genome are widely used in human identity testing and forensic casework, and most commercial kits available are based on multiplex amplification of common 10-16 STR loci with each analysis range specifically established in some populations. Therefore, this system may miss unusually small or large repeats beyond predefined analysis range. Here, we report unusually large repeats of 25-, 26- and novel 30-repeat in PentaE locus, suggesting that it may not be so rare in a certain population and necessitating extensive validation process of multiplex system prior to introduction into the population concerned.

Comparison of modified multiple-locus variable-number tandem-repeat fingerprinting with pulsed-field gel electrophoresis for typing clinical isolates of Staphylococcus aureus.

Background: Multiple-locus variable-number tandem-repeat fingerprinting (MLVF) is based on multiplex PCR, utilizing variable number tandem repeat. Our goal was to compare the performance of MLVF in distinguishing clinical Staphylococcus aureus isolates with that of pulsed-field gel electrophoresis (PFGE), which has traditionally been the gold standard.

Methods: Sixty-three clinically significant S.

Impact of vitamin D receptor gene polymorphisms on clinical outcomes of HLA-matched sibling hematopoietic stem cell transplantation.

We hypothesized that polymorphisms of the vitamin D receptor (VDR) gene might affect clinical outcomes of allogeneic hematopoietic stem cell transplantation (HSCT). Three VDR gene polymorphisms (BsmI G>A, ApaI G>T, and TaqI T>C) were genotyped in 147 patients who underwent HLA-matched sibling allogeneic HSCT. Frequencies of infection, graft-vs.

A case of brain abscess caused by Propionibacterium acnes 13 months after neurosurgery and confirmed by 16S rRNA gene sequencing.

Propionibacterium acnes is a gram-positive anaerobic bacillus and a normal inhabitant of the skin. Although it is often considered a contaminant of blood cultures, it can occasionally cause serious infections, including postoperative central nervous system infections. Here, we report the case of a 70-yr-old man who developed a large cerebral abscess caused by P.

False homozygous deletions of SMN1 exon 7 using Dra I PCR-RFLP caused by a novel mutation in spinal muscular atrophy.

Spinal muscular atrophy (SMA) is an autosomal recessive neuromuscular disorder, and about 95% of SMA patients are homozygous for deletions in the SMN1 gene. Herein, classical polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP) using DraI yielded false homozygous deletions of SMN1 exon 7 in a patient with SMA, but multiple ligation-dependent probe amplification analysis revealed one remaining copy of SMN1 exon 7. Sequencing showed that this false deletion in the PCR-RFLP resulted from a novel mutation of one SMN1 copy that was not deleted (c.

Fetus-in-fetu in the cranium of a 4-month-old boy: histopathology and short tandem repeat polymorphism-based genotyping. Case report.

Fetus-in-fetu is a very rare condition in which one fetus is contained within another. About 100 cases have been reported, and in most of these the fetus was located in the retroperitoneum. The authors describe an extremely rare case of an intracranial fetus-in-fetu in an extraaxial location.

P2X7 receptor polymorphism and clinical outcomes in HLA-matched sibling allogeneic hematopoietic stem cell transplantation.

Background And Objectives: The P2X7 receptor (P2X7 R) is a key player in the processing and release of interleukin (IL)-1. To evaluate whether the A1513C polymorphism of the P2X7 R gene is related to allogeneic stem cell transplantation outcome, we performed an association analysis between this polymorphism and clinical outcomes in patients treated with an HLA-matched sibling stem cell transplant.

Design And Methods: Patients (n=152) with a malignancy or aplastic anemia underwent allogeneic stem cell transplantation at a single institute.

Glutathione S-transferase A1 polymorphisms and acute graft-vs.-host disease in HLA-matched sibling allogeneic hematopoietic stem cell transplantation.

Busulfan and the metabolites of cyclophosphamide are conjugated with glutathione and catabolized by enzymes of the cytosolic glutathione S-transferases family. There are clearly linked single nucleotide polymorphisms in the promoter region of the glutathione S-transferase A1 gene (i.e.

Polymorphisms of the methylenetetrahydrofolate reductase gene and clinical outcomes in HLA-matched sibling allogeneic hematopoietic stem cell transplantation.

To evaluate whether the C677T and A1298C polymorphisms of 5,10-methylenetetrahydrofolate reductase (MTHFR) are related to the toxicity of methotrexate (MTX) used in allogeneic stem cell transplantation, we performed association analysis between these genetic polymorphisms and the clinical outcomes of patients treated using human leukocyte antigen-matched sibling stem cell transplantation. Patients (n=72) with hematological malignancy or aplastic anemia were given a short course of MTX as a graft-versus-host disease prophylaxis. Patients with the 677TT genotype showed higher total bilirubin levels (677TT vs 677CT vs 677CC, 14.