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Introduction Regional cancer patients face various barriers in accessing specialist cancer services. Teletrials are a new model of care that utilise communications technologies to enable access to and participation in clinical trials close to home. The present study aimed to explore the experiences of regional cancer patients and their carers while participating in a teletrial, and those of regional patients who travelled to a metropolitan centre for trial participation. Methods A concurrent, mixed methods study design was used to address the study aim. Patient quality of life data were gathered for both groups and an audio-recorded semi-structured interview undertaken to explore patients’ and carers’ experiences of the two modes of trial participation. Greater weighting was given to the qualitative data. Results Participants described teletrials as an acceptable and valuable initiative that reduced overall burden of trial participation. Irrespective of mode of delivery, patients and carers identified access to trials and specialist cancer services as an important equity issue for regional cancer patients. Discussion From the perspective of regional cancer patients and carers, a teletrial offers convenient, acceptable access to a clinical trial. Although not all patients may want to engage in a teletrial, patients and carers agree that it offers equity of opportunity for trial participation, irrespective of where people live.

autosomal recessive, X-linked, and mitochondrial SCAs according to the mode of inheritance. Among these, autosomal dominant SCAs is the most common subtype, and more than 30 autosomal dominant SCAs have been identified to date. The causative genes associated with SCAs include SCA1 (ATXN1), SCA2 (ATXN2), SCA3 (ATXN3), SCA5 (SPTBN), SCA6 (CACNA1A), SCA7 (ATXN7), SCA8 Analysis of trinucleotide repetitive sequences for Korean patients with spinocerebellar ataxia types 8, 12, and 17

In intestinal helminth infections, Th2 immune respones are generally associated with mucin secretion for worm expulsion from the host intestine. In particular, IL-4 and IL-13 are the important cytokines related with intestinal mucus production via STAT6 signalling in nematode infections. However, this perspective has never been studied in Gymnophalloides seoi infection. The present study aimed to observe the STAT6 signalling and cytokine responses in C57BL/6 mice, a mouse strain resistant to infection with this trematode. The results showed that worm expulsion occurred actively during days 1-2 post-infection (PI), when goblet cells began to proliferate in the small intestine. The STAT6 gene expression in the mouse spleen became remarkable from day 2 PI. Moreover, G. seoi infection induced a significant increase of IL-13 from day 4 PI in the spleen of infected mice. Our results suggested that goblet cell hyperplasia and worm expulsion in G. seoi-infected mice should be induced by STAT6 signalling, in which IL-13 may be involved as a dominant triggering cytokine.

Methylation-specific (MS) multiplex ligation-dependent probe amplification (MLPA) at two differentially methylated regions (DMRs) at chromosome 11p15, H19-DMR and LIT1-DMR, and microsatellite analysis for uniparental disomy (UPD) at chromosome 7 or 11, have been recommended for the genetic diagnosis of the Beckwith-Wiedemann syndrome (BWS) and the Silver-Russell syndrome (SRS). In this study, the efficacy of the MS pyrosequencing method at H19-DMR and LIT1-DMR at 11p15 and SGCE-DMR at 7q21 was evaluated for the genetic diagnosis of BWS (n=18) and SRS (n=20) patients. Epigenetic alterations or UPD were detected in 83% of BWS and 50% of SRS individuals by MS-MLPA, but the detection rate increased to 95% of BWS and 70% of SRS by MS pyrosequencing. Thirteen BWS patients (72%) harbored loss-of-methylation (LOM) at LIT1-DMR and two patients (11%) harbored gain-of-methylation (GOM) at H19-DMR, whereas two patients (11%) had both LOM at LIT1-DMR and GOM at H19-DMR, reflecting paternal UPD 11. Thirteen SRS patients (65%) harbored LOM at H19-DMR, whereas one patient (5%) had GOM at SGCE-DMR, reflecting maternal UPD 7. Birth anthropometric profiles were significantly correlated to methylation scores at either H19-DMR or LIT1-DMR. In conclusion, MS pyrosequencing enhanced the detection rate of molecular defects in BWS and SRS. Moreover, it indicates that methylation status at 11p15.5 might have an important role in fetal growth.

Introduction and aims: Wide phenotypic and genotypic heterogeneities in Wilson's disease (WD) have been reported, hampering the study of their correlations. The goal of this study was to identify the factors related to these diversities. Methods: Clinical courses and molecular genetic characteristics were analysed in 237 unrelated Korean WD families. The average follow-up period was 8.2 ± 5.8 years. Results: Presenting phenotypes were classified as H1 (12.2%), H2 (42.4%), N1 (21.6%), N2 (0.4%), NX (0.4%), presymptomatic (22.4%) and other (0.4%), modifying the guidelines by Ferenci and colleagues. Age at presentation was youngest and cirrhosis was rarest in the presymptomatic group. Decompensated cirrhosis was the highest in the H1 group. Favourable outcome was rarest in the N1 group. Forty-seven (11 novel) ATP7B mutations were identified in 85% of the 474 alleles. Multiplex ligation-dependent probe amplification assays in ATP7B and analyses of ATOX1 and COMMD1 genes identified no additional mutations. Yeast complementation assays demonstrated functional perturbation of the seven novel missense mutants. Five major mutations, p.Arg778Leu, p.Ala874Val, p.Asn1270Ser, p.Lys838SerfsX35 and p.Leu1083Phe, accounted for 63% of the alleles. H1 was more common, age at presentation was younger and N1+N2+NX tended to be less common in patients with nonsense, frame shifting or splicing mutations than in those with missense mutations alone. Patients with both mutations in the transduction (Td) or the ATP hinge domain showed presymptomatic or hepatic manifestations but no neurological manifestation. Conclusions: The presenting phenotype strongly affects the clinical outcome of WD, and is related to the ATP7B mutation type and location, providing an evidence for genotype–phenotype correlations in WD.

Results: The 12 BWS patients had normal karyotypes. Abnormal methylation patterns in the BWSIC2 (LIT1) region were identified in seven patients (58.3%) using the MS-PCR RFLP method. Conclusions: The MS-PCR RFLP method is a simple, economical genetic test. It detected genetic abnormalities in 50-60% of BWS patients, suggesting that it can be used as a screening test. A more precise method is required, however, to enhance the detection rate of genetic abnormalities, especially in BWSIC1 region.

Objective: To evaluate the role of chemotherapy and/or rituximab for treatment of posttransplant lymphoproliferative disorder (PTLD) in solid organ transplantation. Data Sources: A MEDLINE search (1966–May 2007) was conducted using the key words posttransplant lymphoproliferative disorder, solid organ transplantation, chemotherapy, and rituximab. References of relevant articles and abstracts from recent hematology, oncology, and transplantation scientific meetings (2004–May 2007) were also reviewed. Study Selection and Data Extraction: Prospective and retrospective studies identified from the data sources were evaluated, and all information deemed relevant was included for this review. Data Synthesis: Overall response rates ranged from 53% to 68%, 25% to 83%, and 74% to 100% for rituximab monotherapy, chemotherapy, and chemotherapy plus rituximab, respectively. Positive response to treatment was influenced by prognostic factors, including presence of Epstein-Barr virus in tumor cells, normal lactate dehydrogenase levels, good performance status, early disease onset after transplantation, and early disease stages. These factors in study patients likely contribute to the variability in response rates seen between treatment options. Severe adverse effects, ranging from grade 3 neutropenia to infection resulting in death, occurred more frequently in patients receiving chemotherapy than in patients receiving only rituximab. Conclusions: Although reduction in immunosuppressive medications remains the first-line therapy for PTLD treatment, many cases do not respond to this treatment alone, especially monomorphic or more aggressive cases of lymphoma. Therefore, it is reasonable to begin active treatment including rituximab and/or chemotherapy initially, along with reduction in immunosuppression in many cases. Further prospective, comparative studies are urgently needed to confirm the efficacy of these treatment strategies as well as to clarify which subset of patients may benefit most from them.

Beckwith-Wiedemann syndrome (BWS) is fetal overgrowth syndrome, whereas Silver-Russell syndrome (SRS) is characterized by pre- or postnatal growth retardation. BWS and SRS share molecular epigenetic defects in chromosome 11p15, where two imprinting centers, LIT1-differentially methylated region (MDR) and H19-DMR, exist. A small number of patients with SRS harbor maternal uniparental disomy of chromosome 7q as well. Extensive genetic analyses including methylation specific (MS) PCR-RFLP, MS-MLPA, microsatellite markers or MS-pyrosequencing analysis were performed using genomic DNA obtained from peripheral leukocytes to identify the epigenetic detects in patients with BWS and SRS. Ten out of 14 BWS patients (71.4%) showed hypomethylation in LIT1-DMR. One BWS patient harbored hypermethylation in H19-DMR (7.1%). Two BWS patients had both H19-DMR and LIT1-DMR defects, one of whom has paternal UPD at chr. 11 (14.3%). Eleven out of 13 SRS patients (78.6 %) showed hypomethylation in H19-DMR. One SRS patient (6.7%) had UPD at 7q. With MS-pyrosequencing analysis, epigenetic defects were identified in 93.1% of BWS patients and 85.7% of SRS patients. These positive rates are higher than previously reported positive rates, 80% in BWS and 50% in SRS. In addition, with MS-pyrosequencing analyses, quantification of methylation defects was available, which could identify partial methylation defects that were not revealed by MS-PCR-RFLP or MS-MLPA. The validity of MS-pyrosequencing method for the genetic diagnosis of BWS or SRS is needed to be investigated in a large patient cohort.

Steroid 21-hydroxylase deficiency is caused by inactivating mutations in the CYP21A2 gene. This paper reports on the mutation spectrum and the genotype-phenotype correlation of 21-hydroxylase deficiency. 72 unrelated patients with congenital adrenal hyperplasia (CAH) were included. Molecular analysis of CYP21A2 was performed, via the multiplex ligation-dependent probe amplification (MLPA) analysis and sequence-specific differenzial PCR amplification of the CYP21A2 and CYP21A1P genes, using 4 pair-wise sequence-specific primers, followed by sequencing of the entire CYP21A2 gene. Large gene deletions were identified in 45 (31.3%) of the 144 unrelated CAH alleles, whereas the most frequent point mutations were intron 2 splice mutations (c.293-13A>G) (41/144, 28.5%). The MLPA analysis successfully identified 23 of 72 patients (31.9%) with single copy deletion in CYP21A2. This paper describes a rapid and accurate method for the molecular diagnosis of 21-hydroxylase deficiency, which relies on the identification of point mutations and structural rearrangements within the CYP21A2 gene.

Objectives ARC (arthrogryposis, renal dysfunction, and cholestasis) syndrome is a rare, fatal cause of neonatal intrahepatic cholestasis without known treatment modalities and has recently been ascribed to a mutation in the VPS33B gene. We assessed the clinical characteristics and investigated the VPS33B mutations in Korean patients with ARC syndrome. Patients and methods We reviewed the medical records of 6 patients with ARC syndrome among 90 patients with neonatal cholestasis from 2000 to 2005 and assessed the relative incidence rate ratio, clinical symptoms, laboratory findings, and pathological findings. DNA samples from 5 patients, 4 parents, and 2 fetuses were analyzed for VPS33B mutations. Results The relative incidence rate ratio was 1/7 that of biliary atresia (95% CI 0.33-0.06). All 6 patients presented with ichthyosis and recurrent infection, and failed to thrive with the 3 main symptoms. All of the patients died within the age of 12 months. They had various severities of cholestasis, metabolic acidosis, nephrogenic diabetes insipidus, chronic diarrhea, platelet abnormalities, and central nervous system anomalies. We identified 1 novel c.403+2T>A splice-site mutation, 2 frame-shift mutations (c.1509_1510insG, c.790_791del), 1 nonsense mutation (c.661C>A), and 1 known nonsense mutation (c.1518C>T) in the VPS33B gene. Prenatal diagnosis was performed in 2 different families. Conclusions This study indicates that the incidence of ARC syndrome is not as rare as has been thought. We found 4 novel and 1 known mutations in ARC syndrome patients and performed prenatal diagnosis in 2 families, which will facilitate genetic diagnosis and counseling for affected families.

Human Gnathostoma hispidum infection is extremely rare in the world literature and has never been reported in the Republic of Korea. A 74-year-old Korean man who returned from China complained of an erythematous papule on his back and admitted to our hospital. Surgical extraction of the lesion and histopathological examination revealed sections of a nematode larva in the deep dermis. The sectioned larva had 1 nucleus in each intestinal cell and was identified as G. hispidum. The patient recalled having eaten freshwater fish when he lived in China. We designated our patient as an imported G. hispidum case from China.

Fabry disease is an X-linked inborn error of glycosphingolipid catabolism that results from mutations in the gene encoding the alpha-galactosidase A (GLA) enzyme. We have identified 15 distinct mutations in the GLA gene in 13 unrelated patients with classic Fabry disease and 2 unrelated patients with atypical Fabry disease. Two of the identified mutations were novel (i.e., the D231G missense mutation and the L268delfsX1 deletion mutation). This study evaluated the effects of the chemical chaperones 1-deoxygalactonojirimycin (DGJ) on the function of GLA in vitro, in cells containing missense mutations in the GLA gene. Nine missense and a nonsense mutations, including one novel mutation were cloned into mammalian expression vectors. After transient expression in COS-7 cells, GLA enzyme activity and protein expression were analyzed using fluorescence spectrophotometry and Western blot analysis, respectively. DGJ enhanced GLA enzyme activity in the M42V, I91T, R112C and F113L mutants. Interestingly, the I91T and F113L mutations are associated with the atypical form of Fabry disease. However, DGJ treatment did not have any significant effect on the GLA enzyme activity and protein expression of other mutants, including C142W, D231G, D266N, and S297F. Of note, GLA enzyme activity was not detected in the novel mutant (i.e., D231G), although protein expression was similar to the wild type. In the absence of DGJ, the E66Q mutant had wild-type levels of GLA protein expression and approximately 40% GLA activity, indicating that E66Q is either a mild mutation or a functional single nucleotide polymorphism (SNP). Thus, the results of this study suggest that the chemical chaperone DGJ enhances GLA enzyme activity and protein expression in milder mutations associated with the atypical form of Fabry disease.