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Embracing Monogenic Parkinson's Disease: The MJFF Global Genetic PD Cohort

Vollstedt EJ, Schaake S, Lohmann K, Padmanabhan S, Brice A, Lesage S, et al.

Mov Disord, 2023 Feb;38(2):286-303.
PMID: 36692014 DOI: 10.1002/mds.29288

BACKGROUND: As gene-targeted therapies are increasingly being developed for Parkinson's disease (PD), identifying and characterizing carriers of specific genetic pathogenic variants is imperative. Only a small fraction of the estimated number of subjects with monogenic PD worldwide are currently represented in the literature and availability of clinical data and clinical trial-ready cohorts is limited.
OBJECTIVE: The objectives are to (1) establish an international cohort of affected and unaffected individuals with PD-linked variants; (2) provide harmonized and quality-controlled clinical characterization data for each included individual; and (3) further promote collaboration of researchers in the field of monogenic PD.
METHODS: We conducted a worldwide, systematic online survey to collect individual-level data on individuals with PD-linked variants in SNCA, LRRK2, VPS35, PRKN, PINK1, DJ-1, as well as selected pathogenic and risk variants in GBA and corresponding demographic, clinical, and genetic data. All registered cases underwent thorough quality checks, and pathogenicity scoring of the variants and genotype-phenotype relationships were analyzed.
RESULTS: We collected 3888 variant carriers for our analyses, reported by 92 centers (42 countries) worldwide. Of the included individuals, 3185 had a diagnosis of PD (ie, 1306 LRRK2, 115 SNCA, 23 VPS35, 429 PRKN, 75 PINK1, 13 DJ-1, and 1224 GBA) and 703 were unaffected (ie, 328 LRRK2, 32 SNCA, 3 VPS35, 1 PRKN, 1 PINK1, and 338 GBA). In total, we identified 269 different pathogenic variants; 1322 individuals in our cohort (34%) were indicated as not previously published.
CONCLUSIONS: Within the MJFF Global Genetic PD Study Group, we (1) established the largest international cohort of affected and unaffected individuals carrying PD-linked variants; (2) provide harmonized and quality-controlled clinical and genetic data for each included individual; (3) promote collaboration in the field of genetic PD with a view toward clinical and genetic stratification of patients for gene-targeted clinical trials. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Matched MeSH terms: Mutation
Deciphering fungicide resistance in Phytophthora: mechanisms, prevalence, and sustainable management approaches

Naqvi SAH, Farhan M, Ahmad M, Kiran R, Fatima N, Shahbaz M, et al.

World J Microbiol Biotechnol, 2024 Aug 16;40(10):302.
PMID: 39150639 DOI: 10.1007/s11274-024-04108-6

The genus Phytophthora contains more than 100 plant pathogenic species that parasitize a wide range of plants, including economically important fruits, vegetables, cereals, and forest trees, causing significant losses. Global agriculture is seriously threatened by fungicide resistance in Phytophthora species, which makes it imperative to fully comprehend the mechanisms, frequency, and non-chemical management techniques related to resistance mutations. The mechanisms behind fungicide resistance, such as target-site mutations, efflux pump overexpression, overexpression of target genes and metabolic detoxification routes for fungicides routinely used against Phytophthora species, are thoroughly examined in this review. Additionally, it assesses the frequency of resistance mutations in various Phytophthora species and geographical areas, emphasizing the rise of strains that are resistant to multiple drugs. The effectiveness of non-chemical management techniques, including biological control, host resistance, integrated pest management plans, and cultural practices, in reducing fungicide resistance is also thoroughly evaluated. The study provides important insights for future research and the development of sustainable disease management strategies to counter fungicide resistance in Phytophthora species by synthesizing current information and identifying knowledge gaps.

Matched MeSH terms: Mutation
Application of a simple oligonucleotide-directed mutagenesis method for correction of a frameshift mutation

Chee HY, Sazaly AB

JUMMEC, 1997;2:27-30.

Matched MeSH terms: Mutation; Frameshift Mutation
Fulltext Unravelling the link between SARS-CoV-2 mutation frequencies, patient comorbidities, and structural dynamics

Azzeri A, Mohamed NA, Wan Rosli SH, Abdul Samat MN, Rashid ZZ, Mohamad Jamali MA, et al.

PLoS One, 2024;19(3):e0291892.
PMID: 38483913 DOI: 10.1371/journal.pone.0291892

Genomic surveillance is crucial for tracking emergence and spread of novel variants of pathogens, such as SARS-CoV-2, to inform public health interventions and to enforce control measures. However, in some settings especially in low- and middle- income counties, where sequencing platforms are limited, only certain patients get to be selected for sequencing surveillance. Here, we show that patients with multiple comorbidities potentially harbour SARS-CoV-2 with higher mutation rates and thus deserve more attention for genomic surveillance. The relationship between the patient comorbidities, and type of amino acid mutations was assessed. Correlation analysis showed that there was a significant tendency for mutations to occur within the ORF1a region for patients with higher number of comorbidities. Frequency analysis of the amino acid substitution within ORF1a showed that nsp3 P822L of the PLpro protease was one of the highest occurring mutations. Using molecular dynamics, we simulated that the P822L mutation in PLpro represents a system with lower Root Mean Square Deviation (RMSD) fluctuations, and consistent Radius of gyration (Rg), Solvent Accessible Surface Area (SASA) values-indicate a much stabler protein than the wildtype. The outcome of this study will help determine the relationship between the clinical status of a patient and the mutations of the infecting SARS-CoV-2 virus.

Matched MeSH terms: Mutation; Mutation Rate*
Homologous recombination repair gene mutations in Malaysian prostate cancer patients

Saeidi H, Raju CS, Ismail P, Raub SHA, Omar N, Hisyam Bakrin I

Cell Mol Biol (Noisy-le-grand), 2022 Aug 31;68(8):22-26.
PMID: 36800845 DOI: 10.14715/cmb/2022.68.8.4

Genetic alterations in the homologous recombination repair (HRR) genes are associated with an increased risk of prostate cancer development, and patients harboring these mutations can benefit from targeted therapy. The main aim of this study is to identify genetic alterations in HRR genes as a potential target for targeted treatment. In this study, targeted next generation sequencing (NGS) is used to analyze mutations in the protein-coding regions of the 27 genes involved in HRR and mutations in hotspots of 5 cancer-associated genes in four FFPE samples and three blood samples from prostate cancer patients. We identified two mutations in TP53 and KRAS. We also identified four conflicting interpretations of pathogenicity variants in BRCA2, STK11 genes and one variant of uncertain significance in the RAD51B gene. In addition, we detected one drug response variant in TP53, and two novel variants in CDK12 and ATM. Our results revealed some actionable pathogenic and potential pathogenic variants that may be associated with response to the Poly (ADP-ribose) polymerase (PARP) inhibitor treatment. More studies in a larger cohort are needed to evaluate and determine the association of HRR mutations with prostate cancer.

Matched MeSH terms: Mutation
Insights into the Structural Complexities of SARS-CoV-2 for Therapeutic and Vaccine Development

AlMatar M, Ramli ANM, Albarri O, Yi CX

Comb Chem High Throughput Screen, 2023;26(11):1945-1959.
PMID: 36366840 DOI: 10.2174/1386207326666221108095705

SARS-CoV-2 is a disease that endangers both human life and the economy. There was an 11- month period of relative evolutionary standstill following the appearance of SARS-CoV-2 in late 2019. However, the emergence of clusters of mutations known as' variants of concern 'with variable viral properties such as transmissibility and antigenicity defined the evolution of SARS-CoV-2. Several efforts have been made in recent months to understand the atomic level properties of SARS-CoV-2. A review of the literature on SARS-CoV-2 mutations is offered in this paper. The critical activities performed by different domains of the SARS-CoV-2 genome throughout the virus's entry into the host and overall viral life cycle are discussed in detail. These structural traits may potentially pave the way for the development of a vaccine and medication to combat the SARS-CoV-2 sickness.

Matched MeSH terms: Mutation
New risk factors and molecular landscapes of hepatic angiosarcoma in the Taiwanese population†

Chung F, Zavadil J

J Pathol, 2024 Jan;262(1):1-3.
PMID: 37929656 DOI: 10.1002/path.6224

Hepatic angiosarcoma is a rare, highly aggressive malignancy of the liver. The tumorigenesis of hepatic angiosarcoma has been relatively understudied in terms of aetiology and molecular properties. A recent study published in The Journal of Pathology revealed a strong association between hepatic angiosarcoma incidence and chronic kidney disease, particularly in end-stage renal disease using population-based data from the National Health Insurance Research Database in Taiwan and an institutional cohort. The study also revealed enrichment in the mutational signature of aristolochic acid exposure and is the first reported observation of this mutational signature in human sarcomas. © 2023 The Pathological Society of Great Britain and Ireland.

Matched MeSH terms: Mutation
Fulltext An Overview of the Genetic Variations of the SARS-CoV-2 Genomes Isolated in Southeast Asian Countries

Yap PSX, Tan TS, Chan YF, Tee KK, Kamarulzaman A, Teh CSJ

J Microbiol Biotechnol, 2020 Jul 28;30(7):962-966.
PMID: 32627759 DOI: 10.4014/jmb.2006.06009

Monitoring the mutation dynamics of human severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is critical in understanding its infectivity, virulence and pathogenicity for development of a vaccine. In an "age of mobility," the pandemic highlights the importance and vulnerability of regionalization and labor market interdependence in Southeast Asia. We intend to characterize the genetic variability of viral populations within the region to provide preliminary information for regional surveillance in the future. By analyzing 142 complete genomes from South East Asian (SEA) countries, we identified three central variants distinguished by nucleotide and amino acid changes.

Matched MeSH terms: Mutation*
Fulltext Increased yield performance of mutation induced Soybean genotypes at varied agro-ecological conditions

Bhuiyan MSH, Malek MA, Emon RM, Khatun MK, Khandaker MM, Alam MA

Braz J Biol, 2022;84:e255235.
PMID: 35019108 DOI: 10.1590/1519-6984.255235

In soybean breeding program, continuous selection pressure on traits response to yield created a genetic bottleneck for improvements of soybean through hybridization breeding technique. Therefore an initiative was taken to developed high yielding soybean variety applying mutation breeding techniques at Plant Breeding Division, Bangladesh Institute of Nuclear Agriculture (BINA), Bangladesh. Locally available popular cultivar BARI Soybean-5 was used as a parent material and subjected to five different doses of Gamma ray using Co60. In respect to seed yield and yield attributing characters, twelve true breed mutants were selected from M4 generation. High values of heritability and genetic advance with high genotypic coefficient of variance (GCV) for plant height, branch number and pod number were considered as favorable attributes for soybean improvement that ensure expected yield. The mutant SBM-18 obtained from 250Gy provided stable yield performance at diversified environments. It provided maximum seed yield of 3056 kg ha-1 with highest number of pods plant-1 (56). The National Seed Board of Bangladesh (NSB) eventually approved SBM-18 and registered it as a new soybean variety named 'Binasoybean-5' for large-scale planting because of its superior stability in various agro-ecological zones and consistent yield performance.

Matched MeSH terms: Mutation/genetics
Fulltext Unraveling POLN germline mutations in familial nasopharyngeal carcinoma: Complementary evidence from gene association and molecular studies

Chong PP

EBioMedicine, 2022 Dec;86:104326.
PMID: 36335666 DOI: 10.1016/j.ebiom.2022.104326
Matched MeSH terms: Germ-Line Mutation*
Fulltext Exome sequencing identifies breast cancer susceptibility genes and defines the contribution of coding variants to breast cancer risk

Wilcox N, Dumont M, González-Neira A, Carvalho S, Joly Beauparlant C, Crotti M, et al.

Nat Genet, 2023 Sep;55(9):1435-1439.
PMID: 37592023 DOI: 10.1038/s41588-023-01466-z

Linkage and candidate gene studies have identified several breast cancer susceptibility genes, but the overall contribution of coding variation to breast cancer is unclear. To evaluate the role of rare coding variants more comprehensively, we performed a meta-analysis across three large whole-exome sequencing datasets, containing 26,368 female cases and 217,673 female controls. Burden tests were performed for protein-truncating and rare missense variants in 15,616 and 18,601 genes, respectively. Associations between protein-truncating variants and breast cancer were identified for the following six genes at exome-wide significance (P

Matched MeSH terms: Mutation, Missense/genetics
Structural investigation, computational analysis, and theoretical cryoprotectant approach of antifreeze protein type IV mutants

Eskandari A, Leow TC, Rahman MBA, Oslan SN

Eur Biophys J, 2024 Nov;53(7-8):385-403.
PMID: 39327310 DOI: 10.1007/s00249-024-01719-7

Antifreeze proteins (AFPs) have unique features to sustain life in sub-zero environments due to ice recrystallization inhibition (IRI) and thermal hysteresis (TH). AFPs are in demand as agents in cryopreservation, but some antifreeze proteins have low levels of activity. This research aims to improve the cryopreservation activity of an AFPIV. In this in silico study, the helical peptide afp1m from an Antarctic yeast AFP was modeled into a sculpin AFPIV, to replace each of its four α-helices in turn, using various computational tools. Additionally, a new linker between the first two helices of AFPIV was designed, based on a flounder AFPI, to boost the ice interaction activity of the mutants. Bioinformatics tools such as ExPASy Prot-Param, Pep-Wheel, SOPMA, GOR IV, Swiss-Model, Phyre2, MODFOLD, MolPropity, and ProQ were used to validate and analyze the structural and functional properties of the model proteins. Furthermore, to evaluate the AFP/ice interaction, molecular dynamics (MD) simulations were executed for 20, 100, and 500 ns at various temperatures using GROMACS software. The primary, secondary, and 3D modeling analysis showed the best model for a redesigned antifreeze protein (AFP1mb, with afp1m in place of the fourth AFPIV helix) with a QMEAN (Swiss-Model) Z score value of 0.36, a confidence of 99.5%, a coverage score of 22%, and a p value of 0.01. The results of the MD simulations illustrated that AFP1mb had more rigidity and better ice interactions as a potential cryoprotectant than the other models; it also displayed enhanced activity in limiting ice growth at different temperatures.

Matched MeSH terms: Mutation*
Intelligent mutation based evolutionary optimization algorithm for genomics and precision medicine

Singh SP, Yadav DK, Chamran MK, Perera DG

Funct Integr Genomics, 2024 Jul 22;24(4):128.
PMID: 39037544 DOI: 10.1007/s10142-024-01401-3

In this paper, genomics and precision medicine have witnessed remarkable progress with the advent of high-throughput sequencing technologies and advances in data analytics. However, because of the data's great dimensionality and complexity, the processing and interpretation of large-scale genomic data present major challenges. In order to overcome these difficulties, this research suggests a novel Intelligent Mutation-Based Evolutionary Optimization Algorithm (IMBOA) created particularly for applications in genomics and precision medicine. In the proposed IMBOA, the mutation operator is guided by genome-based information, allowing for the introduction of variants in candidate solutions that are consistent with known biological processes. The algorithm's combination of Differential Evolution with this intelligent mutation mechanism enables effective exploration and exploitation of the solution space. Applying a domain-specific fitness function, the system evaluates potential solutions for each generation based on genomic correctness and fitness. The fitness function directs the search toward ideal solutions that achieve the problem's objectives, while the genome accuracy measure assures that the solutions have physiologically relevant genomic properties. This work demonstrates extensive tests on diverse genomics datasets, including genotype-phenotype association studies and predictive modeling tasks in precision medicine, to verify the accuracy of the proposed approach. The results demonstrate that, in terms of precision, convergence rate, mean error, standard deviation, prediction, and fitness cost of physiologically important genomic biomarkers, the IMBOA consistently outperforms other cutting-edge optimization methods.

Matched MeSH terms: Mutation*
Fulltext SARS-CoV-2 journey: from alpha variant to omicron and its sub-variants

Hattab D, Amer MFA, Al-Alami ZM, Bakhtiar A

Infection, 2024 Jun;52(3):767-786.
PMID: 38554253 DOI: 10.1007/s15010-024-02223-y

The COVID-19 pandemic has affected hundreds of millions of individuals and caused more than six million deaths. The prolonged pandemic duration and the continual inter-individual transmissibility have contributed to the emergence of a wide variety of SARS-CoV-2 variants. Genomic surveillance and phylogenetic studies have shown that substantial mutations in crucial supersites of spike glycoprotein modulate the binding affinity of the evolved SARS-COV-2 lineages to ACE2 receptors and modify the binding of spike protein with neutralizing antibodies. The immunological spike mutations have been associated with differential transmissibility, infectivity, and therapeutic efficacy of the vaccines and the immunological therapies among the new variants. This review highlights the diverse genetic mutations assimilated in various SARS-CoV-2 variants. The implications of the acquired mutations related to viral transmission, infectivity, and COVID-19 severity are discussed. This review also addresses the effectiveness of human neutralizing antibodies induced by SARS-CoV-2 infection or immunization and the therapeutic antibodies against the ascended variants.

Matched MeSH terms: Mutation*
Accuracy of Radiomics in the Identification of Extrathyroidal Extension and BRAFV600E Mutations in Papillary Thyroid Carcinoma: A Systematic Review and Meta-analysis

Liu Y, Xiang L, Liu FY, Yahya N, Chai JN, Hamid HA, et al.

Acad Radiol, 2025 Mar;32(3):1385-1397.
PMID: 39765435 DOI: 10.1016/j.acra.2024.11.014

RATIONALE AND OBJECTIVES: Extrathyroidal extension (ETE) and BRAFV600E mutation in papillary thyroid cancer (PTC) increase mortality and recurrence risk. Preoperative identification presents considerable challenges. Although radiomics has emerged as a potential tool for identifying ETE and BRAFV600E mutation, systematic evidence supporting its effectiveness remains insufficient. Therefore, this paper aims to determine the effectiveness of radiomics in detecting ETE and BRAFV600E mutations in PTC.
MATERIALS AND METHODS: PubMed, Web of Science, Cochrane, and Embase databases were searched until May 7th, 2024. The Radiomics Quality Score tool assessed bias risk. Subgroup analyses based on radiomics and clinical characteristics were conducted.
RESULTS: Our systematic review included 19 studies, encompassing 5337 PTC cases. Among these, 12 articles focused on ETE and seven articles focused on BRAFV600E mutations. For the identification of ETE in the validation set, the summarized machine learning (ML) models demonstrated 0.80c-index (95%CI: 0.77-0.83), 0.77 sensitivity (95%CI: 0.72-0.81), and 0.78 specificity (95%CI: 0.73-0.82). Radiomics based on ultrasound demonstrated 0.82c-index (95%CI: 0.78-0.86), 0.77 sensitivity (95%CI: 0.68-0.84), and 0.84 specificity (95%CI: 0.75-0.91). For the identification of BRAFV600E mutations in the validation set, the summarized ML models showed 0.80c-index (95%CI: 0.72-0.87), 0.76 sensitivity (95%CI: 0.67-0.84), and 0.88 specificity (95%CI: 0.77-0.94). ML models based on ultrasound-guided radiomics had 0.81c-index (95%CI: 0.74-0.89), 0.79 sensitivity (95%CI: 0.71-0.86), and 0.87 specificity (95%CI: 0.74-0.94).
CONCLUSION: Radiomics in identifying ETE and BRAFV600E mutation have high c-index, sensitivity, and specificity, especially images from ultrasound, demonstrating the potential for diagnosing ETE and BRAFV600E mutations in PTC.

Matched MeSH terms: Mutation*
Fulltext Infantile Progressive Hepatoencephalomyopathy with Combined OXPHOS Deficiency due to Mutations in the Mitochondrial Translation Elongation Factor Gene GFM1

Balasubramaniam S, Choy YS, Talib A, Norsiah MD, van den Heuvel LP, Rodenburg RJ

JIMD Rep, 2012;5:113-22.
PMID: 23430926 DOI: 10.1007/8904_2011_107

Mitochondrial disorders are a heterogeneous group of often multisystemic and early fatal diseases caused by defects in the oxidative phosphorylation (OXPHOS) system. Given the complexity and intricacy of the OXPHOS system, it is not surprising that the underlying molecular defect remains unidentified in many patients with a mitochondrial disorder. Here, we report the clinical features and diagnostic workup leading to the elucidation of the genetic basis for a combined complex I and IV OXPHOS deficiency secondary to a mitochondrial translational defect in an infant who presented with rapidly progressive liver failure, encephalomyopathy, and severe refractory lactic acidemia. Sequencing of the GFM1 gene revealed two inherited novel, heterozygous mutations: a.539delG (p.Gly180AlafsX11) in exon 4 which resulted in a frameshift mutation, and a second c.688G > A (p.Gly230Ser) mutation in exon 5. This missense mutation is likely to be pathogenic since it affects an amino acid residue that is highly conserved across species and is absent from the dbSNP and 1,000 genomes databases. Review of literature and comparison were made with previously reported cases of this recently identified mitochondrial disorder encoded by a nuclear gene. Although limited in number, nuclear gene defects causing mitochondrial translation abnormalities represent a new, rapidly expanding field of mitochondrial medicine and should potentially be considered in the diagnostic investigation of infants with progressive hepatoencephalomyopathy and combined OXPHOS disorders.

Matched MeSH terms: Mutation; Frameshift Mutation; Mutation, Missense
Fulltext Whole-exome sequencing and bioinformatic analyses revealed differences in gene mutation profiles in papillary thyroid cancer patients with and without benign thyroid goitre background

Eng ZH, Abdullah MI, Ng KL, Abdul Aziz A, Arba'ie NH, Mat Rashid N, et al.

Front Endocrinol (Lausanne), 2022;13:1039494.
PMID: 36686473 DOI: 10.3389/fendo.2022.1039494

BACKGROUND: Papillary thyroid cancer (PTC) is the most common thyroid malignancy. Concurrent presence of cytomorphological benign thyroid goitre (BTG) and PTC lesion is often detected. Aberrant protein profiles were previously reported in patients with and without BTG cytomorphological background. This study aimed to evaluate gene mutation profiles to further understand the molecular mechanism underlying BTG, PTC without BTG background and PTC with BTG background.
METHODS: Patients were grouped according to the histopathological examination results: (i) BTG patients (n = 9), (ii) PTC patients without BTG background (PTCa, n = 8), and (iii) PTC patients with BTG background (PTCb, n = 5). Whole-exome sequencing (WES) was performed on genomic DNA extracted from thyroid tissue specimens. Nonsynonymous and splice-site variants with MAF of ≤ 1% in the 1000 Genomes Project were subjected to principal component analysis (PCA). PTC-specific SNVs were filtered against OncoKB and COSMIC while novel SNVs were screened through dbSNP and COSMIC databases. Functional impacts of the SNVs were predicted using PolyPhen-2 and SIFT. Protein-protein interaction (PPI) enrichment of the tumour-related genes was analysed using Metascape and MCODE algorithm.
RESULTS: PCA plots showed distinctive SNV profiles among the three groups. OncoKB and COSMIC database screening identified 36 tumour-related genes including BRCA2 and FANCD2 in all groups. BRAF and 19 additional genes were found only in PTCa and PTCb. "Pathways in cancer", "DNA repair" and "Fanconi anaemia pathway" were among the top networks shared by all groups. However, signalling pathways related to tyrosine kinases were the most significantly enriched in PTCa while "Jak-STAT signalling pathway" and "Notch signalling pathway" were the only significantly enriched in PTCb. Ten SNVs were PTC-specific of which two were novel; DCTN1 c.2786C>G (p.Ala929Gly) and TRRAP c.8735G>C (p.Ser2912Thr). Four out of the ten SNVs were unique to PTCa.
CONCLUSION: Distinctive gene mutation patterns detected in this study corroborated the previous protein profile findings. We hypothesised that the PTCa and PTCb subtypes differed in the underlying molecular mechanisms involving tyrosine kinase, Jak-STAT and Notch signalling pathways. The potential applications of the SNVs in differentiating the benign from the PTC subtypes requires further validation in a larger sample size.

Matched MeSH terms: Mutation
R243W Mutation in Thyroid Hormone Resistance Syndrome Beta: A Case Report

Ong JC, W Omar WMH, Tuan Ismail TS, Chatterjee K, Hussain S

J ASEAN Fed Endocr Soc, 2024;39(2):81-85.
PMID: 39620185 DOI: 10.15605/jafes.039.02.04

A three-year-old girl with a history of recurrent tonsillitis was investigated for failure to thrive and global developmental delay. Clinically, she had a triangular face with low-set ears and intermittent tachycardia. She had growth failure with her weight under the third centile while her height was within normal limits. Other systemic examinations were unremarkable. The presence of an elevated free T4 (FT4) with an inappropriately high thyroid stimulating hormone (TSH) in this patient raised the clinical suspicion of Thyroid Hormone Resistance Syndrome. DNA sequencing confirmed the diagnosis, which showed R243W gene mutation in Thyroid Hormone Receptor-Beta1 (THRB1).

Matched MeSH terms: Mutation
Fulltext A Hybrid SSA and SMA with Mutation Opposition-Based Learning for Constrained Engineering Problems

Wang S, Liu Q, Liu Y, Jia H, Abualigah L, Zheng R, et al.

Comput Intell Neurosci, 2021;2021:6379469.
PMID: 34531910 DOI: 10.1155/2021/6379469

Based on Salp Swarm Algorithm (SSA) and Slime Mould Algorithm (SMA), a novel hybrid optimization algorithm, named Hybrid Slime Mould Salp Swarm Algorithm (HSMSSA), is proposed to solve constrained engineering problems. SSA can obtain good results in solving some optimization problems. However, it is easy to suffer from local minima and lower density of population. SMA specializes in global exploration and good robustness, but its convergence rate is too slow to find satisfactory solutions efficiently. Thus, in this paper, considering the characteristics and advantages of both the above optimization algorithms, SMA is integrated into the leader position updating equations of SSA, which can share helpful information so that the proposed algorithm can utilize these two algorithms' advantages to enhance global optimization performance. Furthermore, Levy flight is utilized to enhance the exploration ability. It is worth noting that a novel strategy called mutation opposition-based learning is proposed to enhance the performance of the hybrid optimization algorithm on premature convergence avoidance, balance between exploration and exploitation phases, and finding satisfactory global optimum. To evaluate the efficiency of the proposed algorithm, HSMSSA is applied to 23 different benchmark functions of the unimodal and multimodal types. Additionally, five classical constrained engineering problems are utilized to evaluate the proposed technique's practicable abilities. The simulation results show that the HSMSSA method is more competitive and presents more engineering effectiveness for real-world constrained problems than SMA, SSA, and other comparative algorithms. In the end, we also provide some potential areas for future studies such as feature selection and multilevel threshold image segmentation.

Matched MeSH terms: Mutation
Fulltext Whole mitochondrial genome sequencing of Malaysian patients with cardiomyopathy

Kuan SW, Chua KH, Tan EW, Tan LK, Loch A, Kee BP

PeerJ, 2022;10:e13265.
PMID: 35441061 DOI: 10.7717/peerj.13265

Cardiomyopathy (CMP) constitutes a diverse group of myocardium diseases affecting the pumping ability of the heart. Genetic predisposition is among the major factors affecting the development of CMP. Globally, there are over 100 genes in autosomal and mitochondrial DNA (mtDNA) that have been reported to be associated with the pathogenesis of CMP. However, most of the genetic studies have been conducted in Western countries, with limited data being available for the Asian population. Therefore, this study aims to investigate the mutation spectrum in the mitochondrial genome of 145 CMP patients in Malaysia. Long-range PCR was employed to amplify the entire mtDNA, and whole mitochondrial genome sequencing was conducted on the MiSeq platform. Raw data was quality checked, mapped, and aligned to the revised Cambridge Reference Sequence (rCRS). Variants were named, annotated, and filtered. The sequencing revealed 1,077 variants, including 18 novel and 17 CMP and/or mitochondrial disease-associated variants after filtering. In-silico predictions suggested that three of the novel variants (m.8573G>C, m.11916T>A and m.11918T>G) in this study are potentially pathogenic. Two confirmed pathogenic variants (m.1555A>G and m.11778G>A) were also found in the CMP patients. The findings of this study shed light on the distribution of mitochondrial mutations in Malaysian CMP patients. Further functional studies are required to elucidate the role of these variants in the development of CMP.

Matched MeSH terms: Mutation/genetics

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