Distribution of CFTR mutations in Eastern Hungarians: Relevance to genetic testing and to the introduction of newborn screening for cystic fibrosis

AbstractBackgroundThe aim of this study was characterization of an updated distribution of CFTR mutations in a representative cohort of 40 CF patients with the classical form of the disease drawn from Eastern Hungary. Due to the homogeneity of the Hungarian population our data are generally applicable to other regions of the country, including the sizeable diaspora.MethodsWe utilized the recommended “cascade” CFTR mutation screening approach, initially using a commercial assay, followed by examination of the common “Slavic” deletion CFTRdele2,3(21kb). Subsequently, the entire CFTR coding region of the CFTR gene was sequenced in patients with yet unidentified mutations.ResultsThe Elucigene CF29Tm v2 assay detected 81.25% of all CF causing mutations. An addition of the CFTRdele2,3(21kb) increased the mutation detection rate to 86.25%. DNA sequencing enabled us to identify mutations on 79/80 CF alleles. Mutations [CFTRdele2,3(21kb), p.Gln685ThrfsX4 (2184insA) were found at an unusually high frequency, each comprising 5.00% of all CF alleles.ConclusionWe have identified common CF causing mutations in the Hungarian population with the most common mutations (p.Phe508del, p.Asn1303Lys, CFTRdele2,3(21kb), 2184insA, p.Gly542X, and p.Leu101X), comprising over 93.75% of all CF alleles. Obtained data are applicable to the improvement of DNA diagnostics in Hungary and beyond, and are the necessary prerequisite for the introduction of a nationwide “two tier” CF newborn screening program

Visualization of mucosal field in HPV positive and negative oropharyngeal squamous cell carcinomas: combined genomic and radiology based 3D model

The aim of this study was to visualize the tumor propagation and surrounding mucosal field in radiography-based 3D model for advanced stage HNSCC and combine it with HPV genotyping and miRNA expression characterization of the visualized area. 25 patients with T1-3 clinical stage HNSCC were enrolled in mapping biopsy sampling. Biopsy samples were evaluated for HPV positivity and miR-21-5p, miR-143, miR-155, miR-221-5p expression in Digital Droplet PCR system. Significant miRNA expression differences of HPV positive tumor tissue biopsies were found for miR-21-5p, miR-143 and miR-221-5p compared to the HPV negative tumor biopsy series. Peritumoral mucosa showed patchy pattern alterations of miR-21-5p and miR-155 in HPV positive cases, while gradual change of miR-21-5p and miR-221-5p was seen in HPV negative tumors. In our study we found differences of the miRNA expression patterns among the HPV positive and negative tumorous tissues as well as the surrounding mucosal fields. The CT based 3D models of the cancer field and surrounding mucosal surface can be utilized to improve proper preoperative planning. Complex evaluation of HNSCC tissue organization field can elucidate the clinical and molecular differentiation of HPV positive and negative cases, and enhance effective organ saving therapeutic strategies

Genetic and Clinical Predictors of Age of ESKD in Individuals With Autosomal Dominant Tubulointerstitial Kidney Disease Due to UMOD Mutations

n/

Time-frequency analysis of in vivo MRS of the breast improves cancer detection

The presence of a choline resonance at 3.23ppm has been shown by several groups to be a diagnostic marker for invasive breast cancer in vivo. In our previous studies MRS was undertaken prior to biopsy. However, in this study the patients had biopsies and biopsy clips prior to the MRS, causing blood in the lesion to degrade the local field homogeneity. The use of spectral windowing methods, such as the short-time Fourier transform (STFT), may help in the identification of choline by providing access to both frequency and time information simultaneously

Lobular neoplasia detected at MRI-guided biopsy: imaging findings and outcomes

OBJECTIVE: To review MRI findings of pure lobular neoplasia (LN) on MRI guided biopsy, evaluate surgical and clinical outcomes, and assess imaging findings predictive of upgrade to malignancy. METHODS: HIPAA compliant, IRB-approved retrospective review of our MRI-guided breast biopsy database from October 2008-January 2015. Biopsies yielding atypical lobular hyperplasia or lobular carcinoma in situ were included in the analysis; all biopsy slides were reviewed by a dedicated breast pathologist. Imaging indications, MRI findings, and histopathology were reviewed. Statistical analysis was performed using the two-tailed Fisher exact-test and the t-test, and 95% CIs were determined. A p \u3c 0.05 was considered statistically significant. RESULTS: Database search yielded 943 biopsies in 785 patients of which 65/943 (6.9%) reported LN as the highest risk pathologic lesion. Of 65 cases, 32 were found to have LN as the dominant finding on pathology and constituted the study population. All 32 findings were mammographically and sonographically occult. Three of 32 (9.3%) cases of lobular neoplasia were upgraded to malignancy, all LCIS (one pleomorphic and two classical). The most common MRI finding was focal, heterogenous non-mass enhancement with low T2 signal. No clinical features or imaging findings were predictive of upgrade to malignancy. CONCLUSION: Incidence of pure lobular neoplasia on MRI guided biopsy is low, with comparatively low incidence of upgrade to malignancy. No imaging or clinical features are predictive of upgrade on surgical excision, therefore, prudent radiologic-pathologic correlation is necessary

Requirement of Phosphatidylglycerol for Maintenance of Photosynthetic Machinery

Phosphatidylglycerol (PG) is a ubiquitous component of thylakoid membranes. Experiments with the pgsA mutant of the cyanobacterium Synechocystis sp. PCC6803 defective in biosynthesis of PG have demonstrated an indispensable role of PG in photosynthesis. In the present study, we have investigated the light susceptibility of the pgsA mutant with regard to the maintenance of the photosynthetic machinery. Growth of the mutant cells without PG increased the light susceptibility of the cells and resulted in severe photoinhibition of photosynthesis upon a high-light treatment, whereas the growth in the presence of PG was protected against photoinhibition. Photoinhibition induced by PG deprivation was mainly caused by an impairment of the restoration process. The primary target of the light-induced damage in thylakoid membranes, the D1 protein of photosystem (PS) II was, however, synthesized and degraded with similar rates irrespective of whether the mutant cells were incubated with PG or not. Intriguingly, it was found that instead of the synthesis of the D1 protein, the dimerization of the PSII core monomers was impaired in the PG-deprived mutant cells. Addition of PG to photoinhibited cells restored the dimerization capacity of PSII core monomers. These results suggest that PG plays an important role in the maintenance of the photosynthetic machinery through the dimerization and reactivation of the PSII core complex