Correction: Identification of Novel Pathogenic Sequence Variants of the Mismatch Repair Genes During Screening for Lynch Syndrome in a Single Centre of Eastern Hungary.

The original version of this article unfortunately contained a mistake. The variants listed in Table 3 of the original version of this article are not in line with the latest HGVS (Human Genome Variation Society) nomenclature (version 19.01).

Identification of Novel Pathogenic Sequence Variants of the Mismatch Repair Genes During Screening for Lynch Syndrome in a Single Centre of Eastern Hungary.

INTRODUCTION: Lynch syndrome is an autosomal dominant disorder, most frequent leading to colon cancer. Identification of patients with Lynch syndrome and screening of their family members are available prevention approach that can significantly decrease mortality. Unfortunately, routine screening still does not belong to standard of care in Hungary. In this study, we performed a comprehensive screening in order to identify patients with mismatch repair (MMR) mutation between the years of 2011 and 2014. Identified mutations were compared with those already published in the international databases. PATIENTS AND METHODS: Patients who underwent treatment for colorectal cancer at the Surgical Institute of the University of Debrecen were screened using the modified Amsterdam and Bethesda Criteria. Immunohistochemistry and microsatellite analyses were performed in order to identify possible mutation carrier cases. Suspicious cases underwent DNA sequencing to detect mutations in the mismatch repair genes (hMLH1, hMSH2). RESULTS: All together 760 colorectal cancer patients were screened. A total of 28 patients were identified as possible MMR mutation carrier and underwent further genetic evaluation. Pathogenic sequence variants of the MMR gene were found in 5 patients. Hypermethylation of the promoter region of the hMLH1 gene was identified in 2 patients. Two out of the 5 pathogenic sequence variants of the MMR gene were first identified by our group while other 2 mutations were previously published as possible founder mutations. CONCLUSION: Identification of families with Lynch syndrome, while challenging because of variable phenotypes at diagnosis, is feasible with available molecular biological technologies and crucial to reduce mortality caused by this syndrome.

[Significance of the monitoring and screening for hereditary nonpolyposis colorectal carcinoma syndrome patients by presenting a case of a family tree]. / A hereditaer nonpolyposus colorectalis carcinoma szindrómás betegek szurésének és szoros utánkövetésének fontossága egy családfa bemutatása kapcsán.

INTRODUCTION: Hereditary nonpolyposis colorectal carcinoma (HNPCC) is an autosomal dominant disease, which shows familial clustering. AIM: We would like to emphasize the importance of monitoring the HNPCC syndrome patients by presenting a case of a proven MMR gene mutation carrier and her family tree encompassing 10 years. MATERIALS AND METHOD: To screen a suspected HNPCC Hungarian family member we are taking thorough family histories. If the diagnosis of HNPCC was further supported by immunohistology and the microsatellite status, sequencing of the MMR genes was carried out. RESULTS: A novel mutation in exon 6 of the hMSH2 gene leading to the deletion of two nucleotide pairs [c.969-970delTC] was detected in our patient. During the 10-year follow-up period of our patient new HNPCC-associated tumors have developed in several family members. Conslusion: Close surveillance of the patient and its family members at risk was effective, although it requires compliance from the subjects. Orv Hetil. 2017; 158(30): 1182-1187.

[Novel treatment opportunities in Graves' orbitopathy]. / Új lehetoségek az endokrin orbitopathia kezelésében.

Graves' orbitopathy is the most common extrathyroidal manifestation of Graves' disease. Up to now, curative treatment modalities for the most severe sight-threatening cases have not been developed. Here the authors summarize the treatment protocol of Graves' orbitopathy and review novel therapeutic options. They review the literature on this topic and present their own clinical experience. The authors point out that anti-CD20 antibody could positively influence the clinical course of Graves' orbitopathy. Selenium is efficient in mild cases. Further prospective investigations are warranted.

The impact of 99mTc-DTPA orbital SPECT in patient selection for external radiation therapy in Graves' ophthalmopathy.

OBJECTIVE: In Graves' ophthalmopathy (GO), there is a demand to differentiate the immunologically active disease state, when immunosuppressive therapy is necessary, from the inactive state, when the patient would not benefit from it. We measured the inflammatory activity in the retrobulbar region using Tc-diethylene triamine pentaacetic acid (DTPA) SPECT before and after external radiation to determine whether this method is suitable for predicting the effectiveness of this therapy. MATERIALS AND METHODS: Thirty-two patients with suspected active GO were involved in this retrospective study. The initial image, DTPA uptake value (UV) and its change after therapy were assessed to monitor the effect of the therapy and investigate whether a pretreatment scan is capable of predicting the outcome. RESULTS: Depending on the change in DTPA UV after radiotherapy, three patient groups were formed: decreased, increased or minimally changed (less than 1×10 injected dose (ID)/ml). The initial DTPA UVs of these groups were significantly different (P<0.001). Improvement was observed mainly in patients with higher initial values. When comparing the groups with low (<12×10 ID/ml) versus high (≥12×10 ID/ml) initial uptake, an unexpected increase was observed in the first group after therapy (mean: +2.89±2.66×10 ID/ml), whereas the average change in the DTPA UV was negative in the latter group as anticipated (-2.24±4.47×10 ID/ml, P<0.00001). CONCLUSION: We found that in GO patients a high DTPA UV may predict the response to orbital radiation therapy. DTPA orbital SPECT may be a suitable technique for the selection of GO patients for radiation therapy.

Q48P mutation in the hMLH1 gene associated with Lynch syndrome in three Hungarian families.

Lynch syndrome (Hereditary nonpolyposis colorectal cancer, HNPCC) is an inherited disease with variable phenotype causing the development of colon cancer and other malignancies. The basis of the disease is believed to be the mismatch repair gene mutations. Genetic screening has been performed among the patients who have undergone surgery for colon cancer at the University of Debrecen, Department of Surgery. Tumor samples of the screened patients were submitted to immunohistochemistry on hMLH1, hMSH2 and hMSH6 genes, microsatellite instability testing, followed by sequencing and multiple ligation dependent probe amplification. Three families were identified with the missense mutation c.143A>C (p.Q48P) of hMLH1 gene. In one of the families a segregation analysis of this particular variant was also accomplished. The segregation analysis revealed a clear correlation between the tumor cases and the occurrence of this mutation. However, none of the analyzed 100 healthy controls demonstrated the same aberration. There is only one published evidence in the literature about the presence of this rare variant in any population. The Gln to Pro switch in the ATPase domain, a conservative region of the hMLH1 gene, creates significant changes in the protein structure. These results indicate that this mutation is the abnormality responsible for the patients' phenotype and it is feasible that this particular aberration occurs more frequently among Hungarian Lynch syndrome patients.