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  1. Takaoka H, Suzuki T
    Trop Med Health, 2015 Nov;43(Suppl):87-94.
    PMID: 26744576 DOI: 10.2149/tmh.2015-S13
    Recent studies on the epidemiology and control of Guatemalan onchocerciasis, chiefly made by the Guatemala-Japan Cooperative Project on Onchocerciasis Research and Control, are reviewed. Epidemiological features of Guatemalan onchocerciasis are summarized as to characteristic altitudinal distribution of endemic areas, disease manifestation, vector taxonomy, biology and transmission dynamic of the disease. Extensive insecticide studies in the field and laboratory demonstrate that the characteristic situations of Guatemalan streams where Simulium ochraceum, the main vector of onchocerciasis, breeds require ingenious methods of larviciding. Finally, the feasibility of an area vector control is indicated by the successful control operation in the San Vicente Pacaya Pilot Area, in which a new fixed-dose larviciding method was applied.
  2. Liong ML, Suzuki T, Yamanaka H, Kurokawa K, Daikuzono N, Nakazato M
    J Clin Laser Med Surg, 1994 Apr;12(2):85-92.
    PMID: 10151050
    Prostalase¿ has a probe that emits a laser beam at 360 degrees . Targeted obstructive prostatic adenoma tissue was heated to above the cytotoxic threshold temperature of 45 degrees C. After successful canine prostate study, from September 1992 to April 1993, 45 patients were treated. This paper reports the 9 months results of this initial cohort of patients. Prostatic and periprostatic temperature mapping showed the mean temperature within the adenoma zone was 49 degrees C, while the periprostatic tissue remained within the safety level of less than 42.5 degrees C. The mean prostate volume reductions at 3, 6, and 9 months were 36, 33, and 38%, respectively. Those patients whose surgery was unsuccessful had prostatic tissue removed by TURP at 2 to 3 months. This tissue revealed a definite zone of coagulative necrosis. For the clinical assessment, patients were divided into urine retention (UR) and nonretention (NR) subgroups. At 9 months, 20 of the 32 UR subgroup and 10 of the 13 NR subgroup patients were available for assessment. Due to poor response or complications, 6 of the 26 UR patients (23%) required ancillary treatment. Hence, 20 of the 26 cases (77%) remained catheter free and their mean maximum uroflow +/- SE was 9.6 +/- 0.7 ml/sec. Based on a Siroky normogram only 7 of these 26 patients (27%) became unobstructed. Two of the 12 NR subgroup patients (17%) required ancillary treatment. The mean maximum uroflow +/- SE was 10.7 +/- 1.2 ml/sec.(ABSTRACT TRUNCATED AT 250 WORDS)
  3. Tiede A, Abdul Karim F, Jiménez-Yuste V, Klamroth R, Lejniece S, Suzuki T, et al.
    Haematologica, 2021 07 01;106(7):1902-1909.
    PMID: 32327501 DOI: 10.3324/haematol.2019.241554
    During factor VIII prophylaxis for severe hemophilia A, bleeding risk increases with time when factor VIII activity is below 1%. Maintaining trough activity above 1% does not protect all patients from bleeding. The relationship between factor VIII activity during prophylaxis and bleeding risk has not been thoroughly studied. We investigated factor VIII activity and annualized bleeding rate for spontaneous bleeds during prophylaxis. A population pharmacokinetic model derived from three clinical trials was combined with dosing data and bleed information from patient diaries. Each patients' time on prophylaxis was divided into five categories of predicted activity (0-1%, >1-5%, >5-15%, >15-50%, and >50%). Exposure time, mean factor VIII activity, and bleed number (from patient diaries) were calculated for each activity category, and annualized bleeding rates estimated using negative binomial regression and a parametric model. Relationships between these bleeding rates and factor VIII activity were evaluated by trial phase (pivotal vs. extension) and age (adults/adolescents [≥12 years] vs. children [0-<12 years]). In total (N=187; 815 patient-years' exposure), factor VIII activity was predicted to reach >1% for 85.64% of the time. Annualized bleeding rate decreased as factor VIII activity increased in each trial phase and age group. However, for a given activity level, bleeding rate differed substantially by trial phase, and age. This suggests that bleeding risk can change over time and is influenced by factors independent of factor VIII pharmacokinetics and trough levels. Target trough and prophylactic regimen should consider patient age, joint disease activity, and other bleeding risk determinants.
  4. Nakamoto H, Amaya Y, Komatsu T, Suzuki T, Dohmae N, Nakamura Y, et al.
    Biochem. J., 2018 08 16;475(15):2559-2576.
    PMID: 30045873 DOI: 10.1042/BCJ20180230
    Hsp90 is an ATP-dependent molecular chaperone that assists folding and conformational maturation/maintenance of many proteins. It is a potential cancer drug target because it chaperones oncoproteins. A prokaryotic homolog of Hsp90 (HtpG) is essential for thermo-tolerance in some bacteria and virulence of zoonotic pathogens. To identify a new class of small molecules which target prokaryotic and eukaryotic Hsp90s, we studied the effects of a naturally occurring cyclic sesquiterpene, zerumbone, which inhibits proliferation of a wide variety of tumor cells, on the activity of Hsp90. Zerumbone enhanced the ATPase activity of cyanobacterial Hsp90 (Hsp90SE), yeast Hsp90, and human Hsp90α. It also enhanced the catalytic efficiency of Hsp90SE by greatly increasing kcat Mass analysis showed that zerumbone binds to cysteine side chains of Hsp90SE covalently. Mutational studies identified 3 cysteine residues (one per each domain of Hsp90SE) that are involved in the enhancement, suggesting the presence of allosteric sites in the middle and C-terminal domains of Hsp90SE Treatment of cyanobacterial cells with zerumbone caused them to become very temperature-sensitive, a phenotype reminiscent of cyanobacterial Hsp90 mutants, and also decreased the cellular level of linker polypeptides that are clients for Hsp90SE Zerumbone showed cellular toxicity on cancer-derived mammalian cells by inducing apoptosis. In addition, zerumbone inhibited the binding of Hsp90/Cdc37 to client kinases. Altogether, we conclude that modification of cysteine residues of Hsp90 by zerumbone enhances its ATPase activity and inhibits physiological Hsp90 function. The activation of Hsp90 may provide new strategies to inhibit its chaperone function in cells.
  5. Yeong KY, Khaw KY, Takahashi Y, Itoh Y, Murugaiyah V, Suzuki T
    Bioorg Chem, 2020 01;94:103403.
    PMID: 31711765 DOI: 10.1016/j.bioorg.2019.103403
    Studies have suggested that sirtuin inhibition may have beneficial effects on several age-related diseases such as neurodegenerative disorders and cancer. Garcinia mangostana is a well-known tropical plant found mostly in South East Asia with several positive health effects. Some of its phytochemicals such as α-mangostin was found to be able to modulate sirtuin activity in mice and was implicated with inflammation, diabetes and obesity. However, comprehensive studies on sirtuin activity by the prenylated xanthones extracted from Garcinia mangostana have yet to be reported. The present study led to the discovery and identification of γ-mangostin as a potent and selective SIRT2 inhibitor. It was demonstrated that γ-mangostin was able to increase the α-tubulin acetylation in MDA-MD-231 and MCF-7 breast cancer cells. It was also found to possess potent antiproliferative activity against both cell lines. In addition, it was able to induce neurite outgrowth in the N2a cells.
  6. Bhandari D, Ozaki A, Suzuki T, Kotera Y, Shrestha S, Horiuchi S, et al.
    BMJ Open, 2022 Feb 17;12(2):e054915.
    PMID: 35177454 DOI: 10.1136/bmjopen-2021-054915
    OBJECTIVES: The detrimental impacts of abuse on victims' well-being are well documented globally, including Japan. The ongoing COVID-19 pandemic may increase the incidence of abuse in the community, creating an additional burden amid the crisis. However, the incidence of abuse in Japan during COVID-19 remains to be evaluated. Accordingly, our study aimed to assess the incidence of physical and verbal abuse among the general population in Japan and to identify the associated factors of abuse during COVID-19.

    DESIGN AND SETTING: We used the data obtained from a nationwide, cross-sectional internet survey conducted in Japan between August and September 2020. Sampling weights were used to calculate national estimates, and multivariable logistic regression was performed to identify the associated factors for physical and verbal abuse.

    RESULTS: Out of the total 25 482 participants, 965 (3.8 %) reported experiencing physical abuse and 1941 (7.6%) verbal abuse from April 2020 to September 2020. The incidence of physical and verbal abuse was higher among female participants. Participants who lived in areas where the 'state of emergency' was enforced were more likely to suffer from physical abuse. Similarly, vulnerable participants such as those below age 18, with low income, bad family relationships, and disabled people were more likely to experience both physical and verbal abuse. Participants suffering from COVID-19-related symptoms, who had poor health status and widows/divorcees were more likely to be verbally abused. Furthermore, those who did not follow preventive behaviours such as wearing masks in public places, abusing drugs and drinking alcohol in high amounts were also more likely to experience abuse.

    CONCLUSION: The impact of abuse was found disproportionately greater in more vulnerable groups of the population. Pandemic has reinforced the existing social inequalities, which need to be addressed timely to prevent precarious repercussions.

  7. Yamamoto T, Tsunematsu Y, Hara K, Suzuki T, Kishimoto S, Kawagishi H, et al.
    Angew Chem Int Ed Engl, 2016 05 17;55(21):6207-10.
    PMID: 27072782 DOI: 10.1002/anie.201600940
    Geometric isomerization can expand the scope of biological activities of natural products. The observed chemical diversity among the pseurotin-type fungal secondary metabolites is in part generated by a trans to cis isomerization of an olefin. In vitro characterizations of pseurotin biosynthetic enzymes revealed that the glutathione S-transferase PsoE requires participation of the bifunctional C-methyltransferase/epoxidase PsoF to complete the trans to cis isomerization of the pathway intermediate presynerazol. The crystal structure of the PsoE/glutathione/presynerazol complex indicated stereospecific glutathione-presynerazol conjugate formation is the principal function of PsoE. Moreover, PsoF was identified to have an additional, unexpected oxidative isomerase activity, thus making it a trifunctional enzyme which is key to the complexity generation in pseurotin biosynthesis. Through the study, we identified a novel mechanism of accomplishing a seemingly simple trans to cis isomerization reaction.
  8. Hayashi M, Murakami T, Kuroda Y, Takai H, Ide H, Awang A, et al.
    Can. J. Vet. Res., 2016 Jul;80(3):189-96.
    PMID: 27408331
    Rotavirus B (RVB) infection in cattle is poorly understood. The objective of this study was to describe the epidemiological features of repeated outbreaks of epidemic diarrhea due to RVB infection in adult cattle on a large dairy farm complex in Japan. In October 2002, approximately 550 adult cows and approximately 450 in February 2005 had acute watery diarrhea at several farms on the complex. Four months before the first outbreak, RVB antibody-positive rates at subsequently affected farms were significantly lower than at non-affected farms (30% to 32% versus 61% to 67%). During the acute phase of both outbreaks, RVB antibody-positive rates in diarrheal cows tested were as low as 15% to 26%. Most of the farms affected in the second outbreak were also involved in the first outbreak. Some adult cows with RVB diarrhea in the first outbreak showed not only RVB seroresponse, but also RVB shedding in the second outbreak, although none of these cows developed diarrhea. Nucleotide sequences of the VP7 and VP4 genes revealed a close relationship between RVB strains in both outbreaks. Taken together, these results indicate that outbreaks of epidemic RVB diarrhea in adult cows might be influenced by herd immunity and could occur repeatedly at the same farms over several years. To our knowledge, this is the first report on repeated RVB infections in the same cattle.
  9. Matsuguma Y, Takada H, Kumata H, Kanke H, Sakurai S, Suzuki T, et al.
    Arch Environ Contam Toxicol, 2017 Aug;73(2):230-239.
    PMID: 28534067 DOI: 10.1007/s00244-017-0414-9
    Microplastics (<5 mm) were extracted from sediment cores collected in Japan, Thailand, Malaysia, and South Africa by density separation after hydrogen peroxide treatment to remove biofilms were and identified using FTIR. Carbonyl and vinyl indices were used to avoid counting biopolymers as plastics. Microplastics composed of variety of polymers, including polyethylene (PE), polypropylene (PP), polystyrene (PS), polyethyleneterphthalates (PET), polyethylene-polypropylene copolymer (PEP), and polyacrylates (PAK), were identified in the sediment. We measured microplastics between 315 µm and 5 mm, most of which were in the range 315 µm-1 mm. The abundance of microplastics in surface sediment varied from 100 pieces/kg-dry sediment in a core collected in the Gulf of Thailand to 1900 pieces/kg-dry sediment in a core collected in a canal in Tokyo Bay. A far higher stock of PE and PP composed microplastics in sediment compared with surface water samples collected in a canal in Tokyo Bay suggests that sediment is an important sink for microplastics. In dated sediment cores from Japan, microplastic pollution started in 1950s, and their abundance increased markedly toward the surface layer (i.e., 2000s). In all sediment cores from Japan, Thailand, Malaysia, and South Africa, the abundance of microplastics increased toward the surface, suggesting the global occurrence of and an increase in microplastic pollution over time.
  10. Dao HV, Uesugi A, Uchida H, Watanabe R, Matsushima R, Lim ZF, et al.
    Toxins (Basel), 2021 09 15;13(9).
    PMID: 34564661 DOI: 10.3390/toxins13090657
    In the coastal countries of Southeast Asia, fish is a staple diet and certain fish species are food delicacies to local populations or commercially important to individual communities. Although there have been several suspected cases of ciguatera fish poisoning (CFP) in Southeast Asian countries, few have been confirmed by ciguatoxins identification, resulting in limited information for the correct diagnosis of this food-borne disease. In the present study, ciguatoxin-1B (CTX-1B) in red snapper (Lutjanus bohar) implicated in a CFP case in Sabah, Malaysia, in December 2017 was determined by single-quadrupole selected ion monitoring (SIM) liquid chromatography/mass spectrometry (LC/MS). Continuous consumption of the toxic fish likely resulted in CFP, even when the toxin concentration in the fish consumed was low. The identification of the fish species was performed using the molecular characterization of the mitochondrial cytochrome c oxidase subunit I gene marker, with a phylogenetic analysis of the genus Lutjanus. This is the first report identifying the causative toxin in fish-implicated CFP in Malaysia.
  11. Shimizu A, Takada H, Koike T, Takeshita A, Saha M, Rinawati, et al.
    Sci Total Environ, 2013 May 1;452-453:108-15.
    PMID: 23500404 DOI: 10.1016/j.scitotenv.2013.02.027
    Seven sulfonamides, trimethoprim, five macrolides, lincomycin and three tetracyclines were measured in 150 water samples of sewage, livestock and aquaculture wastewater, and river and coastal waters, in five tropical Asian countries. The sum of the concentrations of the target antibiotics in sewage and heavily sewage-impacted waters were at sub- to low-ppb levels. The most abundant antibiotic was sulfamethoxazole (SMX), followed by lincomycin and sulfathiazole. The average concentration of SMX in sewage or heavily sewage-impacted waters was 1720 ng/L in Vietnam (Hanoi, Ho Chi Minh, Can Tho; n=15), 802ng/L in the Philippines (Manila; n=4), 538 ng/L in India (Kolkata; n=4), 282 ng/L in Indonesia (Jakarta; n=10), and 76 ng/L in Malaysia (Kuala Lumpur; n=6). These concentrations were higher than those in Japan, China, Europe, the US and Canada. A predominance of sulfonamides, especially SMX, is notable in these tropical countries. The higher average concentrations, and the predominance of SMX, can be ascribed to the lower cost of the antibiotics. Both the concentration and composition of antibiotics in livestock and aquaculture wastewater varied widely. In many cases, sulfamethazine (SMT), oxytetracycline (OTC), lincomycin, and SMX were predominant in livestock and aquaculture wastewater. Both human and animal antibiotics were widely distributed in the respective receiving waters (i.e., the Mekong River and Manila Bay). SMT/SMX ratios indicate a significant contribution from livestock wastewater to the Mekong River and nearby canals, with an estimated ~10% of river water SMX derived from such wastewater. Mass flow calculations estimate that 12 tons of SMX is discharged annually from the Mekong River into the South China Sea. Riverine inputs of antibiotics may significantly increase the concentration of such antibiotics in the coastal waters.
  12. Gatellier L, Ong SK, Matsuda T, Ramlee N, Lau FN, Yusak S, et al.
    Asian Pac J Cancer Prev, 2021 Sep 01;22(9):2945-2950.
    PMID: 34582666 DOI: 10.31557/APJCP.2021.22.9.2945
    The COVID-pandemic has shown significant impact on cancer care from early detection, management plan to clinical outcomes of cancer patients. The Asian National Cancer Centres Alliance (ANCCA) has put together the 9 "Ps" as guidelines for cancer programs to better prepare for the next pandemic. The 9 "Ps" are Priority, Protocols and Processes, Patients, People, Personal Protective Equipments (PPEs), Pharmaceuticals, Places, Preparedness, and Politics. Priority: to maintain cancer care as a key priority in the health system response even during a global infectious disease pandemic. Protocol and processes: to develop a set of Standard Operating Procedures (SOPs) and have relevant expertise to man the Disease Outbreak Response (DORS) Taskforce before an outbreak. Patients: to prioritize patient safety in the event of an outbreak and the need to reschedule cancer management plan, supported by tele-consultation and use of artificial intelligence technology. People: to have business continuity planning to support surge capacity. PPEs and Pharmaceuticals: to develop plan for stockpiles management, build local manufacturing capacity and disseminate information on proper use and reduce wastage. Places: to design and build cancer care facilities to cater for the need of triaging, infection control, isolation and segregation. Preparedness: to invest early on manpower building and technology innovations through multisectoral and international collaborations. Politics: to ensure leadership which bring trust, cohesion and solidarity for successful response to pandemic and mitigate negative impact on the healthcare system.
  13. Chen LK, Liu LK, Woo J, Assantachai P, Auyeung TW, Bahyah KS, et al.
    J Am Med Dir Assoc, 2014 Feb;15(2):95-101.
    PMID: 24461239 DOI: 10.1016/j.jamda.2013.11.025
    Sarcopenia, a newly recognized geriatric syndrome, is characterized by age-related decline of skeletal muscle plus low muscle strength and/or physical performance. Previous studies have confirmed the association of sarcopenia and adverse health outcomes, such as falls, disability, hospital admission, long term care placement, poorer quality of life, and mortality, which denotes the importance of sarcopenia in the health care for older people. Despite the clinical significance of sarcopenia, the operational definition of sarcopenia and standardized intervention programs are still lacking. It is generally agreed by the different working groups for sarcopenia in the world that sarcopenia should be defined through a combined approach of muscle mass and muscle quality, however, selecting appropriate diagnostic cutoff values for all the measurements in Asian populations is challenging. Asia is a rapidly aging region with a huge population, so the impact of sarcopenia to this region is estimated to be huge as well. Asian Working Group for Sarcopenia (AWGS) aimed to promote sarcopenia research in Asia, and we collected the best available evidences of sarcopenia researches from Asian countries to establish the consensus for sarcopenia diagnosis. AWGS has agreed with the previous reports that sarcopenia should be described as low muscle mass plus low muscle strength and/or low physical performance, and we also recommend outcome indicators for further researches, as well as the conditions that sarcopenia should be assessed. In addition to sarcopenia screening for community-dwelling older people, AWGS recommends sarcopenia assessment in certain clinical conditions and healthcare settings to facilitate implementing sarcopenia in clinical practice. Moreover, we also recommend cutoff values for muscle mass measurements (7.0 kg/m(2) for men and 5.4 kg/m(2) for women by using dual X-ray absorptiometry, and 7.0 kg/m(2) for men and 5.7 kg/m(2) for women by using bioimpedance analysis), handgrip strength (<26 kg for men and <18 kg for women), and usual gait speed (<0.8 m/s). However, a number of challenges remained to be solved in the future. Asia is made up of a great number of ethnicities. The majority of currently available studies have been published from eastern Asia, therefore, more studies of sarcopenia in south, southeastern, and western Asia should be promoted. On the other hand, most Asian studies have been conducted in a cross-sectional design and few longitudinal studies have not necessarily collected the commonly used outcome indicators as other reports from Western countries. Nevertheless, the AWGS consensus report is believed to promote more Asian sarcopenia research, and most important of all, to focus on sarcopenia intervention studies and the implementation of sarcopenia in clinical practice to improve health care outcomes of older people in the communities and the healthcare settings in Asia.
  14. Gatellier L, Shankar A, Dewi LKM, Hussain QM, Dendup Wangdi T, Sukumaran DB, et al.
    Asian Pac J Cancer Prev, 2021 Mar 01;22(3):681-690.
    PMID: 33773529 DOI: 10.31557/APJCP.2021.22.3.681
    OBJECTIVE: The COVID-19 pandemic has dramatically affected healthcare services around Asia. The Asian National Cancer Centres Alliance and the Asia-Pacific Organisation for Cancer Prevention collaborated to assess the mid- and long- term impact of COVID-19 to cancer care in Asia.

    METHODS: The two entities organised a combined symposium and post-meeting interactions among representatives of major cancer centres from seventeen Asian countries to outlining major challenges and countermeasures.

    RESULTS: Participating stakeholders distilled five big questions. 1) "Will there be an explosion of late-stage cancers after the pandemic?" To address and recover from perceived delayed prevention, screening, treatment and care challenges, collaboration of key stakeholders in the region and alignment in cancer care management, policy intervention and cancer registry initiatives would be of essential value. 2) "Operations and Finance" The pandemic has resulted in significant material and financial casualties. Flagged acute challenges (shortages of supplies, imposition of lockdown) as well as longer-standing reduction of financial revenue, manpower, international collaboration, and training should also be addressed. 3) "Will telemedicine and technological innovations revolutionize cancer care?" Deploying and implementing telemedicine such as teleconsultation and virtual tumour boards were considered invaluable. These innovations could become a new regular practice, leading to expansion of tele-collaboration through collaboration of institutions in the region. 4) "Will virtual conferences continue after the pandemic?" Virtual conferences during the pandemic have opened new doors for knowledge sharing, especially for representatives of low- and middle-income countries in the region, while saving time and costs of travel. 5) "How do we prepare for the next pandemic or international emergency?" Roadmaps for action to improve access to appropriate patient care and research were identified and scrutinised.

    CONCLUSION: Through addressing these five big questions, focused collaboration among members and with international organisations such as City Cancer Challenge will allow enhanced preparedness for future international emergencies.
    .

  15. Naruse M, Murakami M, Katabami T, Kocjan T, Parasiliti-Caprino M, Quinkler M, et al.
    Eur J Endocrinol, 2023 Jan 10;188(1).
    PMID: 36726325 DOI: 10.1093/ejendo/lvac002
    OBJECTIVE: Primary aldosteronism (PA) is one of the most frequent causes of secondary hypertension. Although clinical practice guidelines recommend a diagnostic process, details of the steps remain incompletely standardized.

    DESIGN: In the present SCOT-PA survey, we have investigated the diversity of approaches utilized for each diagnostic step in different expert centers through a survey using Google questionnaires. A total of 33 centers from 3 continents participated.

    RESULTS: We demonstrated a prominent diversity in the conditions of blood sampling, assay methods for aldosterone and renin, and the methods and diagnostic cutoff for screening and confirmatory tests. The most standard measures were modification of antihypertensive medication and sitting posture for blood sampling, measurement of plasma aldosterone concentration (PAC) and active renin concentration by chemiluminescence enzyme immunoassay, a combination of aldosterone-to-renin ratio with PAC as an index for screening, and saline infusion test in a seated position for confirmatory testing. The cutoff values for screening and confirmatory testing showed significant variation among centers.

    CONCLUSIONS: Diversity of the diagnostic steps may lead to an inconsistent diagnosis of PA among centers and limit comparison of evidence for PA between different centers. We expect the impact of this diversity to be most prominent in patients with mild PA. The survey raises 2 issues: the need for standardization of the diagnostic process and revisiting the concept of mild PA. Further standardization of the diagnostic process/criteria will improve the quality of evidence and management of patients with PA.

  16. Uchiyama Y, Yamaguchi D, Iwama K, Miyatake S, Hamanaka K, Tsuchida N, et al.
    Hum Mutat, 2021 01;42(1):50-65.
    PMID: 33131168 DOI: 10.1002/humu.24129
    Many algorithms to detect copy number variations (CNVs) using exome sequencing (ES) data have been reported and evaluated on their sensitivity and specificity, reproducibility, and precision. However, operational optimization of such algorithms for a better performance has not been fully addressed. ES of 1199 samples including 763 patients with different disease profiles was performed. ES data were analyzed to detect CNVs by both the eXome Hidden Markov Model (XHMM) and modified Nord's method. To efficiently detect rare CNVs, we aimed to decrease sequencing biases by analyzing, at the same time, the data of all unrelated samples sequenced in the same flow cell as a batch, and to eliminate sex effects of X-linked CNVs by analyzing female and male sequences separately. We also applied several filtering steps for more efficient CNV selection. The average number of CNVs detected in one sample was <5. This optimization together with targeted CNV analysis by Nord's method identified pathogenic/likely pathogenic CNVs in 34 patients (4.5%, 34/763). In particular, among 142 patients with epilepsy, the current protocol detected clinically relevant CNVs in 19 (13.4%) patients, whereas the previous protocol identified them in only 14 (9.9%) patients. Thus, this batch-based XHMM analysis efficiently selected rare pathogenic CNVs in genetic diseases.
  17. Sekiguchi F, Tsurusaki Y, Okamoto N, Teik KW, Mizuno S, Suzumura H, et al.
    J Hum Genet, 2019 Dec;64(12):1173-1186.
    PMID: 31530938 DOI: 10.1038/s10038-019-0667-4
    Coffin-Siris syndrome (CSS, MIM#135900) is a congenital disorder characterized by coarse facial features, intellectual disability, and hypoplasia of the fifth digit and nails. Pathogenic variants for CSS have been found in genes encoding proteins in the BAF (BRG1-associated factor) chromatin-remodeling complex. To date, more than 150 CSS patients with pathogenic variants in nine BAF-related genes have been reported. We previously reported 71 patients of whom 39 had pathogenic variants. Since then, we have recruited an additional 182 CSS-suspected patients. We performed comprehensive genetic analysis on these 182 patients and on the previously unresolved 32 patients, targeting pathogenic single nucleotide variants, short insertions/deletions and copy number variations (CNVs). We confirmed 78 pathogenic variations in 78 patients. Pathogenic variations in ARID1B, SMARCB1, SMARCA4, ARID1A, SOX11, SMARCE1, and PHF6 were identified in 48, 8, 7, 6, 4, 1, and 1 patients, respectively. In addition, we found three CNVs including SMARCA2. Of particular note, we found a partial deletion of SMARCB1 in one CSS patient and we thoroughly investigated the resulting abnormal transcripts.
  18. Klionsky DJ, Abdelmohsen K, Abe A, Abedin MJ, Abeliovich H, Acevedo Arozena A, et al.
    Autophagy, 2016;12(1):1-222.
    PMID: 26799652 DOI: 10.1080/15548627.2015.1100356
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