మాలిక్యులర్ మరియు జెనెటిక్ మెడిసిన్

???????? ?????‌?? ??????? ????????? ???????? ??????????????? ?????????. ?? ???????? ?????????? ????? '?????????? ????????????' ????? ???? ???????????? ?????? ??????? ?????????? ????????????? ????? ????? ????????? ?????? ???? ????????? ?????. ? ?????? ???????? ???????? ??????? ????????? ??????????? ???????. ?????, ???? mtDNA ??????????‌? ???????? ??????? ???????????? ??????‌?????‌?? ??????????. ???? ??????? ??????? ??????????????? DNA ????? 421 bp ???????? ????????? ????? ????? ????? ??? ?? ???? (??????)???? ??????? ???????? ????? ????? ???????? ????? ????? ???????? ????? ?????-???? ?????? ???? ??????????? ????????? ?????? ????????? ????????????? .

????????????????? ???? ????? ??????? ??????? ????? ????????? ??????? ???????. ? ????? ?????????? ??????????????? ??????? ????????? ?????????. ? ????? ???????? ?????????? ?????????? ??????‌?????‌?? ?????????? ?????. ???????? ??????????? ???????? ???????????? ????? ? ????? ?????????? ??????????????? ??? ???? ?????????? ???????? ??????‌?????. ???????????? ????????? ????? ??????????? ????? ??????????? ??????, ???????????? ????????? ????? ????? ???? ??????????? ???????????, ????????? ?????? ????? ?????, ???????????? ???????? ????? ????? ?????? ????? ????? ?????????? ??????????? ????? ??????? ??????? ????? ????????? ??????? ????. ?????????.

???????????????? 50 ????????? ???? ?????? ?????? ???? 3.7 ?????????? ???? ?????? ???? ??????????? ???????? ??????????? ????? (HSV) ????????? ????? ???????? ????? ?????????. ???????? ???????????? ???????????, HSV ??????? ????? ????????? ??????????? ???????? ????? ??????????? ???????????? ?????? ????? ????, ?????? ?????? ?????????? ?????? (AD) ???? ???? ????????????. ?????????? ????? ????????????????? ?????? ???? ?????????? ?????? ?? ?????????? ??????????? ????? ?????????? ???????????? ? ?????-?????? ???????. ???????? ?????? ??????????? ?????? ????? ??????? AD ??????? ????? ????????? ?????? ????? ???????, ??? HSV-1, HSV-2, ??????? ???????? ????? 6 (HHV-6), ????? HHV-7. ????????????????‌?? ????????????????? ???? ??????????? ???? ??????? ????? ????????? ?????????, ?????? ????????? ????????? ????????‌? (APP), ????? ???‌???????‌?? ????????????? ????? ????????? ???? (Aβ) ?????????? ???????????? ????? ?? ????????????????? ????????? (NFT) ??????? ?????? ???????. ??? ???? ??????? ????????? ????? ???????? ????? AD ??????? ??????? ???????? ???????????. AD ????????? ??????? ????????? ???????????????? HSV ???????? ??????????????. ??????, ????? ???? ????? ???????????????? ?????? ???? ??? ???????? ????????? ????????????? ???? ????? ???????? ??????? ???????????, HSV ?????????? ???????????? ?????? ?? ????????? ?????? ????????????????, ??????? ???????? ????????????? ?? ??????????? ??? ???????. , ????? ????.?.?? ??????????? ?????????.

??????? 2015??, ????? ?????????? ??? ???? (NCLB) ???????? ??????????? ???? ????????, ????? ???????? ????‌????? ?????? ?????? ?????????? ?????????? ???????? ( ???? ???? ???.) ????????????? . NCLB ?????? ????? ?????????? ??????, ?????? ???? ???? (5-20 ???.??. ?????), ????????? ????? ???? ???? ????? ?????????????? ??????? ???? ?????? ????????? ?????? ??????????. Exserohilum turcicum (Pass.) ???????????????? ??? ????? ????????????? ????? ?????? ????????? ??????? ???? PDA ???????? ?????? ?????????. PDA???? E. ??????? ????? ??????? ?????? ????? ?????? ?????? ????? ?????? ??????????. ????????? ??????? ?????? ???????? ???????, ????? ???????? ????? ???? ???? ??????????????????? ???????? ????????. ????????? ???? ??? ????? ?????????? ?????? ???? ???????, ????? ????????? ??????? 56 ????? 89 μm ?????, 9 ????? 13 μm ??????? ????? ?????? ????? 6-10 ???? ???????. ???????? 4-9 ??????????????, ????? ???????? ???? ???? ?????? ??? ???????. ???????? (1987) ?????????? ????? ??????? ? ???????‌?? E. ????????‌?? ??????????? . ????????? ???????? ???????????????, PCR ?????????????? ?????????? ???????‌??? ????????? ???????????????, TUBUF2 ????????? (5' CGGTAACAACTGGGCCAAGG-3') ????? TUBUR1 ??????? (5'-CCTGGTACTGCTGGTACTCAG-3') ????? 1000-bp ?????????? ??????????. ???????????? ??????? , ?????????? ??? ?. ???????? (????????? ????? ?? ?????? ????? ?????? ???????, ??? ????????? ?????????? NCLB ???????? ??????? E. ???????? ????? ????? ???????. ????????? ?????????? ??????? ???????? ?????????????? ? ?????? ??????? ???????? ????? ??????? ?????????? ????????? ?????? ???????????? ????? ????.

?????? ????????? ????? ?????? ???????? ???????? ?????????, ??? ?????????? ????????? ????????????, ??? ????? ?????????? ????????? ????? ??????? ???????? ???????. ?????????? ?????? ??????? ??????????? ?????????‌?? ??????????? 30 ???? ????????? ?????? ????????? ?????? ???? ????????????. BS ????? ??????????? ???????? ???????????, ??????? ???-?????????? ????????????????? ??????? ????? ?????? ???????? ??????????? ????? ??? ????????? ???????? ???????????????. ???? ?????? ????????? ???????????????. ???? ?????????? ??????? ???????????? ????? ????????? ?? ?????? ????? ???????????? ?????? ????????????????. ? ??????? CRC ??????????? ????? ????????? ???????????? ???? ????? ?????????? ?????? ????????? ?????? CRC ???????? ???? ???? ????????? ??????????????. ???????, ????? ??????? ???????? ????? ??????????? ?????? ???????? ????????? ???? ???????? ????????????, ????? ????? ????? ??????? ??????? ?????? ????? ?????????? ??????? ??????.

GRCh38 ???? ???? ???? ????????? ????????? ?????? ?????? ????????????? ???? ????? ???????? ????????? ?????-????????? ??????????? ???????????. ?????-???? ????????????? ????????‌? ??????? ????? ????? ????????? ??????? ????????? ???????? ??????????? ????? ??????????? ???????????? ??????????????. ? ?????-????????, ???? ????-????????? ???? ?????????? ??????????????? ????? ? ???????? ????? ???????? ?????? ??????????????? ?????? ??????????? ???????????.

???????????????? ????? ?? ?????? ???????????-?????? ??? ?????? ????? ???????????? ?????? ?? ????????? ??? ?????? ????? ??????????????? ?????? ?????. ???? ???????? ????? ???????????? ???? ???? ?????????, ???? ????? ????????? ????? ????? ???????? ??????? ??????????? ???? ?????????????????? ??????????? ?????? ??????. ? ?????????? ?????? ????? ????????????? ????? ???????????? (MZ) ????? ?????????? (DZ) ?????? ???????????????? ????? ????? ????? ???? ?????????? ??????????? ???????????????. DZ ???? ???? MZ ?????? ?????? ??????? ???? ??????? ????????????, ?????????? ???????? ?????? ( p -value <0.05). ?? ??????? ??????? MZ ???????? ???????????????? ?? ???? ??????????? ????? ???????, ???? ?????? ??????????? ??????????. ???????????????? ????? ???? ?????? ??????????? ?????????? ???? ???? ????? ???????????.

??????‌???? ???? ??????? ????? ???????????? ???????? ???? ????? ?????????? ?????????, ???????????, ??????? ???????? ????? ????????????? ???? ????? ????? ????? ??????? ???????????? ????????? ?????, ????? ????????, ?????, ????? ????? ?????? ????? ???????? ???????????. ??????????? ????????? ??????????? ?????????????????, ??????? ?????? ????? ????? ?????? ???? ??? ??????????????? ????? ???????? ??????????? ?????? ????? ??????. ????????? ??? ??????? (IoT) ????? ?????? ???????, ???? ????? ????????? ???????????‌?? ????? ????? ????? ?????? ?????????? ??????????? ??????????? ?????????? ????????‌? ???? ?????? ????????? ????? ??????? ???????? ???? ????????? ??????? ??????? ??? ???? ?????? ????????? ??????????????. ???? ?????? ????? ????? ?????????? ????. ???????????? ???? ????????? ????? ???????? ???????????, ????? ????? ???? ????‌?? ???????? ?????????? ???????????????????. ???????????? ???? ????????? (EDC) ???? ????? ???? ????? ??????????? ????? ????????? ?????????????. ? ?????? ???? EDC (???????????? ???? ?????????) ????? eCRF (???? ???????? ?????) ????? ?????????? ????????????. ???? ???????? ?????????????? ????? ????? ????? ???????? ???????? ???????????? ??????? ????????? ????????? ??????, ?????? ??????? ?????????, ?????? ?????? ????? ???? ??????? ??????.

WDR45 ??????????? ????????????? ????? X- ??????? ????-??????????? ????????-??????????? ???????????????? (BPAN)?? ??????? ????? ???????????????, ??? ?????????? ????? ?????????? ???????? ???????? ????? ????? ????? (NBIA)?? ????? ???????????????? ????? ?? ???. ????????? ????????? ???????-??????? ??????? ??????‌?????? ??????, ????? ??????????? ????? ????? ????????? ??????, ??????? ?????? ????? ???? ??????? ?????? ???????. ???? 3 ???? ?????? ????????? WDR45 ??????? ????? ??????? 12?? ?? ??? ????????? (c.1040-1041del)?? ????? ??????????? , ??? ??????-??????? ????????????? ?????? ????????? ??????, ???????? ???????????????. ??????? ????????????? ??????????? ????????? ??? ???????????????????? ????? ??????????????, ??????? ??? ?? ???? ??????‌?????? ?????????‌?? ????????????????.

???????: ?????????? ????????? ????? ????????????????? ?????????, ??? DIDMOAD (????????? ?????????? (DI), ????????? ????????? (DM), ??????? ??????? (OA) ????? ?????????). WFS1 ??????????? ?????????/???????? ??????????? ?????????‌?? ????‌?????? ????????? (AR-WS) ????? ???????? ???????? ???????? ???????????, ????? ??????????? ????????????? ???????? ?????????-??-???????????? ????-??????????? ???????? ????? (ADLFNSHL) ?? ?????? ????? ??????. WS ??????? ????????? ???????? ????? ?????? ????? ?????? ???????????? ??????????????.
???????: ?????????? WS ???? ??????? ????????? ???????? ????? ?????? ????? ??????????????? ???????????? ????? ?????? ??? ????? ?????? ???????.
?????? ????? ???????? : 6 ???????? ????? ??????? ???? ?????? ????? ??????????. ????????? ????????? ????? ??????? ????????? 4 ???????? ????? ???????? ???? ???????, ???????? ?????? ????? ???????? ????? WFS1 ??????? ????? ?????????. ??? 2 ?????????? ?????? ?????? ?????? ???????? ?????? ??????? ??????? ????? ?????? ??? ????????????? ?????? ?????? ?????? ???????? ???????? ???? ?????????????????.
???????: 4 ???????? ????? ???????? ???? ?????? WFS1 ????????? ?????????? ????????????? ????? ???????. ?????? ?????? WFS1 ????????? ??????????? ?????????‌?? ????? ???????. ??? ???????? ????????????? WFS1 ???????????????, ?????? 5 ????????????? ???. ???????????? ????? ????????????? WFS1 ??????? ????? ??????? 8 ?? ???????.
???????: WFS1 ??????????? ?????????? ?????????? AR-WS ????? AD-LFNSHL ?????????? ????? ???????. WS ???? ??????? ???? ????‌?????? ??????? 8 ???? ?????????? ????????? ??????????‌?? ???? ???????? ????????????. ????????? ???????????????, ?????? ????????? ????? ??????. ????, ??????? ?????/???? ???????? ?????? ??????? ???????? ???? ???? ???????, WS ????? ?????????? ?????? ???????????.

??????-?? ????????????? ????? ??????????? ?????????? ????? DNA ?????? ?????????? ?????????? ???????????? ?????????. ????????? DNA ???????? (23andMe, ??????????? DNA, ???????? ???? DNA ?????? ??????? ?????) ? ????????? ?????? ???????? ?????? ????? ????????? ?????? ???????????????. ????????? ????? ?????? ???????? ?????????? 15 ?????????? ???? ????? ????????? ????????????. ? ???????? ?? ???? DNA ?????? ?????? ????????? ?????? ???? ????????????? ???? ????????? ????????. ?????????? ????? ????????????‌??? ????? ????? (Mt ????? Y) ????? ???????? ?? ???? ??????? ?????, ???? DNA ?????? ????? ???? ????? ????????????? ??????????‌?? ???????, ???????, ?????????, ????‌????, ????????? ???? ????? ???????????? ??????.

The advancements in understanding of biological mechanisms in RCCs have led to the development and application of targeted therapies. The FDA approved targeted therapies are mainly directed against angiogenesis, mTOR pathways, and immune checkpoint inhibition. VEGF overexpression due to VHL gene mutation or alteration in majority of RCCs makes it one of the most suitable targets for development of therapy. Inhibitors and antibodies against VEGF or VEGFR have shown promising results in metastatic RCCs. mTOR pathway inhibition has also proven to be an efficacious strategy as well as antibodies targeting the immune checkpoints allowing T-Cells to attack tumour cells. However, there is need for improvement as certain proportion of patients may either not respond or develop resistance against targeted therapies.

????????‌?? ?????? ????? ?????? ???? ????????? ????-???‌???????? ????????? ???????????? ?????. ????????? ???????? ???????? ???? ????? ????? ????????????, ??????, ????? ????? ??? ?????? ???????????? ????? ???????? ????? ???? ?????? (ED)?? ?????????. ?????, ED?? ???? ?????????? ???????? ??????? ????? ????? ????-?????????? - ???????? ??????????? ???????? (AN) - 5-LOX ???‌???????? ????‌???? ????????‌? ????? ?????? ????????? ?????????????, ??? ?????‌?????? 1 (IL-1), ?????‌?????? 6 (IL-6) ????? ??????? ?????????? ????????? ????? (TNF-α). IL-1, IL-6 ????? TNF-α ????? ??????????? ????????? ????? ???? (NF-κβ) ????? ?????????? ????????????? ??????????????? - ??? ??????
??????????? ????‌?? ?????????? - ??? ????? ????????? ????? ????????????????????-???????? (HPA) ????? ???? ????????? ????????? ?????????. , ???????????? ????? ??????????? ??????????. ED? ????? ?????????????? ?????????? ? ????? ???????? ???????? ????? ??????? ??????? ???????? ?????????; ???????, ?????????‌???????? ?????????? ????? ????? ED??? ???????? AN?? ?????????? ???????? ???????? ????????????. ? ?????????, ? ????????? ???? ED??? IL-1, IL-6 ????? TNF-α ????? ???????? ????????????? ??????????????. ? ??????, ???????????? ???????? ??? ??????? ??????-??????, ????????-???????????, ????? ???‌?????????? NF-κβ 5-LOX ???‌???????? ????‌???? ?????????? ????? ?????????? ????????????????. ??? ??? ?????? ??????? ????????? ?????? ????????? ???????????????? ????? ?????? ????? ED?? ?????????? ?????? ????????? ?????????? ???????????? ?????? ????? ????????? ????? ??????? ??????? ???? ????????????.

Alterations in the MET proto-oncogene, such as amplification or mutations causing exon 14 skipping, promote tumor growth, cellular transformation and invasion and are associated with poor prognosis in many types of cancers. There are several c-Met-targeted agents currently in clinical trials, highlighting the importance on developing accurate, efficient and sensitive technologies for the analysis. This short communication will provide an update on three of the most useful technologies for the detection of c-Met exon 14 skipping abnormalities, namely New Generation Sequencing (NGS), nCounter and qPCR.

Background: Duchenne Muscular Dystrophy (DMD) is a progressive neuromuscular disorder characterized by a relentless clinical course with diagnosis usually established around three to four years of age. DMD is caused by mutations in the dystrophin gene, where deletions and duplications of one or more exons represent the bulk of related genetic aberrations.
Aims and Methods: Our aim in the current study is to analyze the frequency and the distribution pattern of deletions/duplications associated with dystrophin gene exons and assess the mean diagnostic age of DMD in a small Lebanese group of dystrophic patients suspected with DMD/BMD based on observed clinical features.
Results and Discussion: Among 52 samples analyzed, we identified 33 cases (63%) with deletions and two cases (4%) with duplications. Deletions were of variable sizes, ranging from 1 to 47 exons and occurred mostly (78%) in two deletion hotspots (HS), HS1 (18%) and HS2 (60%), covering exons 6-19 and 45-52 respectively. Single exon deletions were even further restricted (90%) to the deletion hotspots, mainly to HS2 (80%). The average age of DMD molecular diagnosis in our subject study was 7 years of age.
Conclusion: Molecular analyses were consistent with those obtained in previous studies, with however an average age of DMD diagnosis significantly later than what is usually reported. Our study illustrates the need to implement early molecular diagnosis in order to institute optimal care, including available targeted treatments, for our patients.

Apparently balanced reciprocal translocations are a common type of chromosome rearrangements with an estimate incidence range from about 1 in 500 to 1 in 625 human newborns. Rearrangements were found both in clinically unaffected individuals and patients with phenotypic abnormalities. Most are inherited, but approximately one in five are de novo events and introduce a risk of abnormal phenotype in 6.1% of prenatal genetic counseling.

Objectives: This paper investigated the pharmacokinetic (PK) change, optimal dose and therapeutic monitoring method of vancomycin in severe burns.
Method: This is a retrospective, matched cohort study. Nine burn patients were included, and each individual was matched with a control critically ill patient. Vancomycin concentrations were analyzed using the first order pharmacokinetic principles to calculate elimination rate constant (K), half-life (t1/2), volume distribution (Vd), total body clearance (CLvancomycin) and the 24-hour area under the curve (AUC24 h). Population PK analysis and Monte Carlo simulation was used to investigate optimal dose.
Results: The mean burn area of the burn group and age was 60% and 20 years-old respectively. The loading dose and daily maintenance dose was significantly higher in burn group than that in control group. Vancomycin clearance was significantly higher (p<0.05) in burns patients when compared to control patients. CLCr (creatinine clearance) was not significantly correlated to CLvancomycin (vancomycin clearance) in both groups. Ctrough (serum trough concentration) was significantly correlated with AUC24h in the control group (r=0.98, R2=0.96, p<0.01), but not in the burn group (r=0.63, R2=0.40, P=0.07). Daily dose of 5000 mg of vancomycin could achieve 90% probability of target attainment if target was AUC24h /MIC (minimum inhibitory concentration)>400.
Conclusion: Two steady state concentrations but not Ctrough is an appropriate reference for vancomycin therapeutic monitoring. A daily dose of at least 5000 mg is suggested in severe burn patients with normal renal function (CLCr>90 mL/min).

Study background: Over the past years, the number of patients diagnosed with glioma has increased. Glioma is the most widespread pediatric malignancy of the brain and a high-grade tumor is associated with a dismal prognosis. Members of the matrix metalloproteases (MMP) enzyme family (especially MMP-2 and MMP-play an important role in the degradation of the extracellular matrix (ECM) a requirement for disease progression, in addition to the miRNAs play a vital role in regulating “cancer hallmarks”.
Aim: Our aim in this study was to detect the expression level of MMP2 and MMP9 in high-grade glioma and low-grade glioma to find the differential expression in two different subtypes and to find the correlation of MMP and progression of disease and to identify any relationship between miRNA and MMP expression in gliomas.
Methods and finding: We determined the expression of all the miRNAs and mRNAs for the (MMP2 and MMP9) in over 20 high grade glioma (HGG) and 20 low grade glioma (LGG) in paraffin-embedded (FFPE) using Quantitative polymerase chain reaction (qPCR).
Result: Seven miRNAs showed high expression specifically in HGG compared to LGG with significant differential expression (p-value ≤ 0.05).
Conclusion: The mRNA for the MMP-2 and MMP-9 were highly expressed in HGG than in LGG, although the difference did not reach the statistical significance. The main limitations of this study are the small sample size of the patients and further work is needed to investigate the relativeness of our work to the clinical side.

??????: ??? ?????????? ?????? ?????? ?????????? ??? RPE65 ????? ???? ???????????? . ? ??????????? ????????? ??????? ???????? ?????? ????????? ?????????????? ???? ???????? ??? ???????? ???? ????????? ?????????????.
????????? ??????: ???????? ????? ???????? ??????? ??????? RPE65 ????????? ?????????, ????? ?????? ?? ???-?????? ????????? ?????????.
???????: ?????? ????????????.
???? ????? ???????: LCA ????? ?????? ????????????? ???????? ??? ???????? ?????. ? ???? ???????????? ???????????? ??????????? ??????? ??????? ??????? ??????? ?????? ????????. ??????? ???????? ????? ????? ?????? ??????????? ????? ????????? ??????????????, ??????? ????????? ?????????? ????????????. ????????? ??????? ???? ????? ??? ? ????????? ????? ?????????? ??????? ??????? ???????? ??????????? ?????????????, ???????? ???????? ????? ?????????? ??????? ?????? ?????? ??????? ???????? ???????????.

??????-??????? ????????? ????? ?????????????? ???????? ????????? ?????????, ??? ????????? ?????????? ????? ?????? ????????? ?????? ?????? ??????????????????. ? ????????? ??????? ????? ???????? LMX1B ??????? ????? ?????????? ??????????? ?????????? ?????????‌?? c.[737G>A], p.([Arg246Gln)]?? ?????????????. ? ???????? 246? ?????? ???? ????? ?????? ????? ?????????? ??????? ???? ???????? ????????? ??????? ????????????????? ????????????? ????? ?????????. 737? ???????? ???? ?????????????? ????? 246? ???????? ???? ????? ????? ????? ????? ????? ???? ????????????????. ??????? ????? ????????? ??????? ??????? ??????????? ????? ?????????? ?????????????????????? (FSGS)?? ????????? LMX1B ????????? ????????? ?????? (NPLRD) ???? ?????? ?????????? ??????????????????, ? ?????????????? ????????‌?????????? ??????????? ??????? ?????? ?????? ??????? ????????? ????? ??? ???????? ???????????? ?????????????. (NPS). ????????? ???????? ???? ???? ???????? ???? ???? ?????? ?????????????????? ?? ???? ??????? ??????????? ???????. ?????? ??????????? ????? ???????? FSGS ?????? ????????? ???????? ?????? ???????????????? ??????????????. ?? ???? ??????? ????? ?????????? ????????? ?????????? ????????, ??? ?? 3 ???????????? ????????????? ??????? ????? ??????? ???? ????????????. ?? ???? ????? ???? ??????????? ?????? ???????, ?????? ???? ??? ????????? ????? ?????? ???????? ????????? ?????? ???????????? ?????? ?????? (ADPKD) ????? ????? ?????? ??????.