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Fulltext A Novel Pathogenic TUBA1A Variant in a Croatian Infant Is Linked to a Severe Tubulinopathy with Walker-Warburg-like Features

Saidin A, Papazovska Cherepnalkovski A, Shaukat Z, Arsov T, Hussain R, Roberts BJ, et al.

Genes (Basel), 2024 Aug 05;15(8).
PMID: 39202391 DOI: 10.3390/genes15081031

Tubulinopathies are associated with malformations of cortical development but not Walker-Warburg Syndrome. Intensive monitoring of a Croatian infant presenting as Walker-Warburg Syndrome in utero began at 21 weeks due to increased growth of cerebral ventricles and foetal biparietal diameter. Monitoring continued until Caesarean delivery at 34 weeks where the infant was eutrophic. Clinical assessment of a progressive neurological disorder of unknown aetiology found a macrocephalic head and markedly hypoplastic genitalia with a micropenis. Neurological examination showed generalized hypotonia with very rare spontaneous movements, hypotonia-induced respiratory insufficiency and ventilator dependence, and generalized myoclonus intensifying during manipulation. With clinical features of hypotonia, lissencephaly, and brain malformations, Walker-Warburg Syndrome was suspected; however, eye anomalies were absent. Genetic trio analysis via whole-exome sequencing only identified a novel de novo mutation in the TUBA1A gene (NM_006009.4:c.848A>G; NP_006000.2:p.His283Arg) in the infant, who died at 2 months of age, as the likely cause. We report a previously unpublished, very rare heterozygous TUBA1A mutation with clinical features of macrocephaly and hypoplastic genitalia which have not previously been associated with the gene. The absence of eye phenotypes or mutations in Walker-Warburg-associated genes confirm this as not a new presentation of Walker-Warburg Syndrome but a novel TUBA1A tubulinopathy for neonatologists to be aware of.

Matched MeSH terms: Mutation
Fulltext Genotypic Detection of rpoB and katG Gene Mutations Associated with Rifampicin and Isoniazid Resistance in Mycobacterium Tuberculosis Isolates: A Local Scenario (Kelantan)

Ismail NA, Ismail MF, Noor SS, Camalxaman SN

Malays J Med Sci, 2016 Jan;23(1):22-6.
PMID: 27540322 MyJurnal

Drug resistant tuberculosis (DR-TB) remains a public health issue that is of major concern on a global scale. The characterisation of clinical isolates may provide key information regarding the underlying mechanisms of drug resistance, and helps to augment therapeutic options. This study aims to evaluate the frequency of gene mutations associated with Rifampicin (RIF) and Isoniazid (INH) resistance among nine clinical isolates.

Matched MeSH terms: Mutation
Fulltext Morphological and biochemical responses of Oryza sativa L. (cultivar MR219) to ion beam irradiation

Ling AP, Ung YC, Hussein S, Harun AR, Tanaka A, Yoshihiro H

J Zhejiang Univ Sci B, 2013 Dec;14(12):1132-43.
PMID: 24302713 DOI: 10.1631/jzus.B1200126

Heavy ion beam, which has emerged as a new mutagen in the mutation breeding of crops and ornamental plants, is expected to result in the induction of novel mutations. This study investigates the morphological and biochemical responses of Oryza sativa toward different doses of carbon ion beam irradiation.

Matched MeSH terms: Mutation/physiology; Mutation/radiation effects*
Fulltext Inherited mutations in BRCA1 and BRCA2 in an unselected multiethnic cohort of Asian patients with breast cancer and healthy controls from Malaysia

Wen WX, Allen J, Lai KN, Mariapun S, Hasan SN, Ng PS, et al.

J Med Genet, 2018 02;55(2):97-103.
PMID: 28993434 DOI: 10.1136/jmedgenet-2017-104947

BACKGROUND: Genetic testing for BRCA1 and BRCA2 is offered typically to selected women based on age of onset and family history of cancer. However, current internationally accepted genetic testing referral guidelines are built mostly on data from cancer genetics clinics in women of European descent. To evaluate the appropriateness of such guidelines in Asians, we have determined the prevalence of germ line variants in an unselected cohort of Asian patients with breast cancer and healthy controls.
METHODS: Germ line DNA from a hospital-based study of 2575 unselected patients with breast cancer and 2809 healthy controls were subjected to amplicon-based targeted sequencing of exonic and proximal splice site junction regions of BRCA1 and BRCA2 using the Fluidigm Access Array system, with sequencing conducted on a Illumina HiSeq2500 platform. Variant calling was performed with GATK UnifiedGenotyper and were validated by Sanger sequencing.
RESULTS: Fifty-five (2.1%) BRCA1 and 66 (2.6%) BRCA2 deleterious mutations were identified among patients with breast cancer and five (0.18%) BRCA1 and six (0.21%) BRCA2 mutations among controls. One thousand one hundred and eighty-six (46%) patients and 97 (80%) carriers fulfilled the National Comprehensive Cancer Network guidelines for genetic testing.
CONCLUSION: Five per cent of unselected Asian patients with breast cancer carry deleterious variants in BRCA1 or BRCA2. While current referral guidelines identified the majority of carriers, one in two patients would be referred for genetic services. Given that such services are largely unavailable in majority of low-resource settings in Asia, our study highlights the need for more efficient guidelines to identify at-risk individuals in Asia.

Matched MeSH terms: Mutation*; Germ-Line Mutation
The spectrum of beta-thalassemia mutations in southern Thailand

Nopparatana C, Panich V, Saechan V, Sriroongrueng V, Nopparatana C, Rungjeadpha J, et al.

Southeast Asian J Trop Med Public Health, 1995;26 Suppl 1:229-34.
PMID: 8629112

Beta-thalassemia mutations in 282 alleles of 253 unrelated individuals originating from various provinces in the south of Thailand were characterized by dot blot hybridization, specific PCR-amplification and direct DNA sequencing. It was possible to characterize the mutations in 274 (97.2%) of alleles studied. Twelve different point mutations and two different large deletions of the beta-globin gene were identified. Seven common mutations, namely 4 bp deletion at codons 41/42. IVS1 position 5 (G-C), codon 19 (AAC-AGC), codon 17 (AAG-TAG), IVS1 position 1 (G-T), position -28 (A-G) and 3.5 kb deletion, accounted for about 91.5%. The mutations at mRNA cap site + 1 (A-C) and IVS1 position 1 (G-A), previously undescribed in Thailand, were found in 1 and 2 individuals, respectively. A novel mutation of 105 bp deletion at the 5' end of beta-globin gene was detected in a family originating from this area. The knowledge from this study should be useful for planning of genetic counseling and prenatal diagnosis programs for patients with beta-thalassemia in the south of Thailand.

Matched MeSH terms: Mutation*; Point Mutation
Fulltext Mutation-specific pathophysiological mechanisms define different neurodevelopmental disorders associated with SATB1 dysfunction

den Hoed J, de Boer E, Voisin N, Dingemans AJM, Guex N, Wiel L, et al.

Am J Hum Genet, 2021 02 04;108(2):346-356.
PMID: 33513338 DOI: 10.1016/j.ajhg.2021.01.007

Whereas large-scale statistical analyses can robustly identify disease-gene relationships, they do not accurately capture genotype-phenotype correlations or disease mechanisms. We use multiple lines of independent evidence to show that different variant types in a single gene, SATB1, cause clinically overlapping but distinct neurodevelopmental disorders. Clinical evaluation of 42 individuals carrying SATB1 variants identified overt genotype-phenotype relationships, associated with different pathophysiological mechanisms, established by functional assays. Missense variants in the CUT1 and CUT2 DNA-binding domains result in stronger chromatin binding, increased transcriptional repression, and a severe phenotype. In contrast, variants predicted to result in haploinsufficiency are associated with a milder clinical presentation. A similarly mild phenotype is observed for individuals with premature protein truncating variants that escape nonsense-mediated decay, which are transcriptionally active but mislocalized in the cell. Our results suggest that in-depth mutation-specific genotype-phenotype studies are essential to capture full disease complexity and to explain phenotypic variability.

Matched MeSH terms: Mutation*; Mutation, Missense
Fulltext Possible Roles of New Mutations Shared by Asian and American Zika Viruses

Yokoyama S, Starmer WT

Mol Biol Evol, 2017 03 01;34(3):525-534.
PMID: 28087772 DOI: 10.1093/molbev/msw270

Originating in Africa, the Zika virus (ZIKV) has spread to Asia, Pacific Islands and now to the Americas and beyond. Since the first isolation in 1947, ZIKV strains have been sampled at various times in the last 69 years, but this history has not been reflected in studying the patterns of mutation accumulation in their genomes. Implementing the viral history, we show that the ZIKV ancestor appeared sometime in 1930-1945 and, at that point, its mutation rate was probably less than 0.2 × 10-3/nucleotide site/year and subsequently increased significantly in most of its descendants. Sustaining a high mutation rate of 4 × 10-3/site/year throughout its evolution, the Ancestral Asian strain, which was sampled from a mosquito in Malaysia, accumulated 13 mutations in the 3'-untranslated region of RNA stem-loops prior to 1963, seven of which generate more stable stem-loop structures and are likely to inhibit cellular antiviral activities, including immune and RNA interference (RNAi) pathways. The seven mutations have been maintained in all Asian and American strains and may be responsible for serious medical problems we are facing today and offer testable hypotheses to examine their roles in molecular interactions during brain development.

Matched MeSH terms: Mutation*; Mutation Rate
Fulltext Mitochondrial DNA mutations in Malaysian female breast cancer patients

Omasanggar R, Yu CY, Ang GY, Emran NA, Kitan N, Baghawi A, et al.

PLoS One, 2020;15(5):e0233461.
PMID: 32442190 DOI: 10.1371/journal.pone.0233461

Cancer development has been ascribed with diverse genetic variations which are identified in both mitochondrial and nuclear genomes. Mitochondrial DNA (mtDNA) alterations have been detected in several tumours which include lung, colorectal, renal, pancreatic and breast cancer. Several studies have explored the breast tumour-specific mtDNA alteration mainly in Western population. This study aims to identify mtDNA alterations of 20 breast cancer patients in Malaysia by next generation sequencing analysis. Twenty matched tumours with corresponding normal breast tissues were obtained from female breast cancer patients who underwent mastectomy. Total DNA was extracted from all samples and the entire mtDNA (16.6kb) was amplified using long range PCR amplification. The amplified PCR products were sequenced using mtDNA next-generation sequencing (NGS) on an Illumina Miseq platform. Sequencing involves the entire mtDNA (16.6kb) from all pairs of samples with high-coverage (~ 9,544 reads per base). MtDNA variants were called and annotated using mtDNA-Server, a web server. A total of 18 of 20 patients had at least one somatic mtDNA mutation in their tumour samples. Overall, 65 somatic mutations were identified, with 30 novel mutations. The majority (59%) of the somatic mutations were in the coding region, whereas only 11% of the mutations occurred in the D-loop. Notably, somatic mutations in protein-coding regions were non-synonymous (49%) in which 15.4% of them are potentially deleterious. A total of 753 germline mutations were identified and four of which were novel mutations. Compared to somatic alterations, less than 1% of germline missense mutations are harmful. The findings of this study may enhance the current knowledge of mtDNA alterations in breast cancer. To date, the catalogue of mutations identified in this study is the first evidence of mtDNA alterations in Malaysian female breast cancer patients.

Matched MeSH terms: DNA Mutational Analysis; Mutation*; Germ-Line Mutation
The opposing roles of NOTCH signalling in head and neck cancer: a mini review

Yap LF, Lee D, Khairuddin A, Pairan MF, Puspita B, Siar CH, et al.

Oral Dis, 2015 Oct;21(7):850-7.
PMID: 25580884 DOI: 10.1111/odi.12309

NOTCH signalling can exert oncogenic or tumour suppressive effects in both solid and haematological malignancies. Similar to T-cell acute lymphoblastic leukaemia (T-ALL), early studies suggested a pro-tumorigenic role of NOTCH in head and neck squamous cell carcinoma (HNSCC), mainly based on the increased expression levels of the genes within the pathway. Recently, data from exome sequencing analyses unexpectedly pointed to a tumour suppressor role for NOTCH in HNSCC by identifying loss-of-function mutations in the NOTCH1 gene in a significant proportion of patients. These data have questioned the accepted role of NOTCH in HNSCC and the possible rationale of targeting NOTCH in this disease. This review summarises the current information on NOTCH signalling in HNSCC and discusses how this pathway can apparently exert opposing effects within the same disease.

Matched MeSH terms: Mutation
Fulltext Multiplex amplification refractory mutation system (MARMS) for the detection of β-globin gene mutations among the transfusion-dependent β-thalassemia Malay patients in Kelantan, Northeast of Peninsular Malaysia

Hanafi S, Hassan R, Bahar R, Abdullah WZ, Johan MF, Rashid ND, et al.

Am J Blood Res, 2014;4(1):33-40.
PMID: 25232503

The aim of this study was to adapt MARMS with some modifications to detect beta mutation in our cohort of thalassemia patients. We focused only on transfusion-dependent thalassemia Malay patients, the predominant ethnic group (95%) in the Kelantanese population. Eight mutations were identified in 46 out of 48 (95.83%) beta thalassemia alleles. Most of the patients (54.2%) were compound heterozygous with co-inheritance Cd 26 (G>A). The frequencies of spectrum beta chain mutation among these patients are presented in Table 2. Among the transfusion dependent beta thalassemia Malay patients studied, 26 patients were found to be compound heterozygous and the main alleles were Cd 26 (G>A). Compound heterozygous mutation of Cd 26 (G>A) and IVS 1-5 (G>C) were 12 (46.2%), Cd 26 (G>A) and Cd 41/42 (TTCT) were 9 (34.6%), Cd 26 (G>A) and IVS 1-1 (G>C) were 2 (7.7%) respectively. Meanwhile the minority were made of a single compound heterozygous of Cd 26 (G>A) and Cd 71/72, Cd 26 (>A) and Cd 17 (A>T), Cd 26 (G>A) and -28 (G>A) respectively. Twenty out of forty six patients were shown to have homozygous of IVS 1-5 (G>C) were 2 (10.0%), Cd 26 (G>A) were 15 (75.0%), Cd 19 (A>G) were 1 (5.0%), and IVS 1-1 (G>T) were 2 (10.0%). The beta chain mutations among the Kelantanese Malays followed closely the distribution of beta chain mutations among the Thais and the Malays of the Southern Thailand. The G-C transition at position 5 of the IVS 1-5 mutation was predominant among the Malay patients. In conclusion, this method has successfully identified the mutation spectrum in our cohort of transfusion-dependent beta thalassemia patients, and this method is equally effective in screening for mutation among thalassemia patients.

Matched MeSH terms: Mutation
Fulltext Keloid scarring: understanding the genetic basis, advances, and prospects

Halim AS, Emami A, Salahshourifar I, Kannan TP

Arch Plast Surg, 2012 May;39(3):184-9.
PMID: 22783524 DOI: 10.5999/aps.2012.39.3.184

Keloid disease is a fibroproliferative dermal tumor with an unknown etiology that occurs after a skin injury in genetically susceptible individuals. Increased familial aggregation, a higher prevalence in certain races, parallelism in identical twins, and alteration in gene expression all favor a remarkable genetic contribution to keloid pathology. It seems that the environment triggers the disease in genetically susceptible individuals. Several genes have been implicated in the etiology of keloid disease, but no single gene mutation has thus far been found to be responsible. Therefore, a combination of methods such as association, gene-gene interaction, epigenetics, linkage, gene expression, and protein analysis should be applied to determine keloid etiology.

Matched MeSH terms: Mutation
Correlations of HBV genotypes, mutations affecting HBeAg expression and HBeAg/ anti-HBe status in HBV carriers

Lim CK, Tan JT, Khoo JB, Ravichandran A, Low HM, Chan YC, et al.

Int J Med Sci, 2006;3(1):14-20.
PMID: 16421626

This study was carried out to determine the effects of hepatitis B virus genotypes, core promoter mutations (A1762G1764-->T1762A1764) as well as precore stop codon mutations (TGG-->TAG) on HBeAg expression and HBeAg/ anti-HBe status. Study was also performed on the effects of codon 15 variants (C1858/ T1858) on the predisposition of precore stop codon mutations (TGG-->TAG). A total of 77 sera samples were analyzed. Fifty one samples were successfully genotyped of which the predominant genotype was genotype B (29/ 51, 56.9 %), followed by genotype C (16/ 51, 31.4 %). Co-infections by genotypes B and C were observed in four samples (7.8 %). To a lesser degree, genotypes D and E (2.0 % each) were also observed. For core promoter mutations, the prevalence was 68.8 % (53/ 77) for A1762G1764 wild-type and 14.3 % (11/ 77) for T1762A1764 mutant while 9.1 % (7/ 77) was co-infected by both strains. The prevalence of codon 15 variants was found to be 42.9 % (33/ 77) for T1858 variant and 16.9 % (13/ 77) for C1858 variant. No TAG mutation was found. In our study, no associations were found between genotypes (B and C) and core promoter mutations as well as codon 15 variants. Also no correlation was observed between HBeAg/ anti-HBe status with genotypes (B and C) and core promoter mutations.

Matched MeSH terms: Mutation
A novel complex mutation of the OTC (ornithine transcarbamylase) gene in a Malaysian pedigree

Khoo AS, Balraj P, Rachedi A, Chin CN, Volpi L

Hum Mutat, 1999 Nov;14(5):448.
PMID: 10533073
Matched MeSH terms: Frameshift Mutation
Whole exome sequencing is an efficient, sensitive and specific method for determining the genetic cause of short-rib thoracic dystrophies

McInerney-Leo AM, Harris JE, Leo PJ, Marshall MS, Gardiner B, Kinning E, et al.

Clin Genet, 2015 Dec;88(6):550-7.
PMID: 25492405 DOI: 10.1111/cge.12550

Short-rib thoracic dystrophies (SRTDs) are congenital disorders due to defects in primary cilium function. SRTDs are recessively inherited with mutations identified in 14 genes to date (comprising 398 exons). Conventional mutation detection (usually by iterative Sanger sequencing) is inefficient and expensive, and often not undertaken. Whole exome massive parallel sequencing has been used to identify new genes for SRTD (WDR34, WDR60 and IFT172); however, the clinical utility of whole exome sequencing (WES) has not been established. WES was performed in 11 individuals with SRTDs. Compound heterozygous or homozygous mutations were identified in six confirmed SRTD genes in 10 individuals (IFT172, DYNC2H1, TTC21B, WDR60, WDR34 and NEK1), giving overall sensitivity of 90.9%. WES data from 993 unaffected individuals sequenced using similar technology showed two individuals with rare (minor allele frequency <0.005) compound heterozygous variants of unknown significance in SRTD genes (specificity >99%). Costs for consumables, laboratory processing and bioinformatic analysis were

Matched MeSH terms: Mutation
Fulltext Functional diversity of biocatalysts: whether to bioprospect or bioengineer?

Benbelgacem, Farah Fadwa, Bellag, Oualid Abdelkader, Soroodi, Fatemeh, Abdul Aziz Ahmad, Hamzah Mohd Salleh, Noorbatcha, Ibrahim Ali

Biological and Natural Resources Engineering Journal, 2019;2(1):64-84.
MyJurnal

Biocatalyst should have sufficient and efficient activity for the intended
biotechnological application. In the quest for novel biocatalyst, there is a need to have a
genetic diversity either by finding it within the astronomically large number of possible
candidates or to obtain it by bioengineering an existing gene supported by various
bioinformatic and molecular engineering tools. Nowadays, it is well-known that a huge
number of microorganisms is unculturable and poses great challenges to access biocatalysts
from these microbes. Metagenomics is one of the methods widely applied to reach out
maximum possible variants to “bioprospect” biocatalysts. On the other hand, other approaches
are available to bioengineer enzymes by modifying the DNA sequence precisely based on the
structure and the function information of the protein in the case of rational design, or by a
brave creation of anarchic mutations of the DNA sequence with directed evolution method. In
this regard, both approaches, whether to bioprospect or to bioengineer biocatalysts have
advantages and disadvantages which will be discussed in this paper.KEY WORDS: Sugar
industry wastewater; aluminium sulphate; primary treatment, ferric chloride; polyaluminium
chloride

Matched MeSH terms: Mutation
Fulltext Malignant Transformation of a Rosette-Forming Glioneuronal Tumor with IDH1 Mutation: A Case Report and Literature Review

Jayapalan RR, Mun KS, Wong KT, Sia SF

World Neurosurg X, 2019 Apr;2:100006.
PMID: 31218281 DOI: 10.1016/j.wnsx.2018.100006

Background: Rosette-forming glioneuronal tumor (World Health Organization grade I) is considered as a benign tumor with very low potential for progression. The potential for malignant transformation of this tumor is not known and has never been reported before in literature.
Case Description: We report a 42-year-old man, diagnosed with rosette-forming glioneuronal tumor of the fourth ventricle with a positive isocitrate dehydrogenase 1 mutation, progressed to glioblastoma after 6 years from diagnosis. We discuss the clinical history, radiological findings, and histopathological characteristic with immunohistochemistry findings observed in this unique case.
Conclusions: Despite being acceptable as benign, based on our observations in this case, there is a potential for malignant transformation of rosette-forming glioneuronal tumor. The role of isocitrate dehydrogenase 1 mutation leading to malignant transformation could not be established as our finding is novel and further prospective studies are required to prove this association.

Matched MeSH terms: Mutation
Fulltext Phytochemical and In Vitro Genotoxicity Studies of Standardized Ficus deltoidea var. kunstleri Aqueous Extract

Muhammad H, Omar MH, Rasid ENI, Suhaimi SN, Mohkiar FH, Siu LM, et al.

Plants (Basel), 2021 Feb 11;10(2).
PMID: 33670296 DOI: 10.3390/plants10020343

The present study was carried out to assess the genotoxicity potential of Ficus deltoidea var. kunstleri aqueous extract (FDAE) using standard in vitro assays. The DNA damage of V79B cells was measured using the alkaline comet assay treated at 0.1 mg/mL (IC10) and 0.3 mg/mL (IC25) of FDAE together with positive and negative controls. For in vitro micronucleus assay, the V79B cells were treated with FDAE at five different concentrations (5, 2.5, 1.25, 0.625, and 0.3125 mg/mL) with and without S9 mixture. The bacteria reverse mutation assay of FDAE was performed on Salmonella typhimurium strains TA98, 100, 1535, 1537, and Escherichia coli strain WP2uvrA using pre-incubation method in the presence or in the absence of an extrinsic metabolic system (S9 mixture). FDAE at 0.1 and 0.3 mg/mL significantly increased DNA damage in both comet tail and tail moment (p < 0.05). No significant changes were detected in the number of micronucleated cell when compared to control. Tested at the doses up to 5000 µg/plate, the FDAE did not increase the number of revertant colonies for all strains. In conclusion, further investigation needs to be conducted in animal model to confirm the non-genotoxicity activities of FDAE.

Matched MeSH terms: Mutation
In silico mutation on a mutant lipase from Acinetobacter haemolyticus towards enhancing alkaline stability

Anuar NFSK, Wahab RA, Huyop F, Halim KBA, Hamid AAA

J Biomol Struct Dyn, 2020 Sep;38(15):4493-4507.
PMID: 31630644 DOI: 10.1080/07391102.2019.1683074

Alkaline-stable lipases are highly valuable biocatalysts that catalyze reactions under highly basic conditions. Herein, computational predictions of lipase from Acinetobacter haemolyticus and its mutant, Mut-LipKV1 was performed to identify functionally relevant mutations that enhance pH performance under increasing basicity. Mut-LipKV1 was constructed by in silico site directed mutagenesis of several outer loop acidic residues, aspartic acid (Asp) into basic ones, lysine (Lys) at positions 51, 122 and 247, followed by simulation under extreme pH conditions (pH 8.0-pH 12.0). The energy minimized Mut-LipKV1 model exhibited good quality as shown by PROCHECK, ERRAT and Verify3D data that corresponded to 79.2, 88.82 and 89.42% in comparison to 75.2, 86.15, and 95.19% in the wild-type. Electrostatic surface potentials and charge distributions of the Mut-LipKV1 model was more stable and better adapted to conditions of elevated pHs (pH 8.0 - 10.0). Mut-LipKV1 exhibited a mixture of neutral and positive surface charge distribution compared to the predominantly negative charge in the wild-type lipase at pH 8.0. Data of molecular dynamics simulations also supported the increased alkaline-stability of Mut-LipKV1, wherein the lipase was more stable at a higher pH 9.0 (RMSD = ∼0.3 nm, RMSF = ∼0.05-0.2 nm), over the optimal pH 8.0 of the wild-type lipase (RMSD = 0.3 nm, RMSF = 0.05-0.20 nm). Thus, the adaptive strategy of replacing surface aspartic acid to lysine in lipase was successful in yielding a more alkaline-stable Mut-LipKV1 under elevated basic conditions.Communicated by Ramaswamy H. Sarma.

Matched MeSH terms: Mutation
Fulltext A comprehensive overview of mitochondrial DNA 4977-bp deletion in cancer studies

Yusoff AAM, Abdullah WSW, Khair SZNM, Radzak SMA

Oncol Rev, 2019 Jan 14;13(1):409.
PMID: 31044027 DOI: 10.4081/oncol.2019.409

Mitochondria are cellular machines essential for energy production. The biogenesis of mitochondria is a highly complex and it depends on the coordination of the nuclear and mitochondrial genome. Mitochondrial DNA (mtDNA) mutations and deletions are suspected to be associated with carcinogenesis. The most described mtDNA deletion in various human cancers is called the 4977-bp common deletion (mDNA4977) and it has been explored since two decades. In spite of that, its implication in carcinogenesis still unknown and its predictive and prognostic impact remains controversial. This review article provides an overview of some of the cellular and molecular mechanisms underlying mDNA4977 formation and a detailed summary about mDNA4977 reported in various types of cancers. The current knowledges of mDNA4977 as a prognostic and predictive marker are also discussed.

Matched MeSH terms: Mutation
Fulltext A dual genetic alteration (mitochondrial and nuclear DNA): first case in Malaysia detected in glioblastoma multiforme

Abdul Aziz Mohamed Yusoff, Wan Salihah Wan Abdullah, Alarmelu Nithya Ramanathan, Jafri Malin Abdullah, Zamzuri Idris

Malaysian Journal of Medicine and Health Sciences, 2020;16(2):332-335.
MyJurnal

Although the precise etiology of Glioblastoma multiforme (GBM, WHO grade IV) remains unknown, its progression
is believed to be driven by the accumulation of multiple genetic alterations. Here, we report a case of a patient who
developed GBM, and associated with dual alterations, particularly 4977-bp deletion in mtDNA (mtDNA4977) and
p.Arg132His (R132H) mutation in IDH1. A 35-year old Malaysian woman patient who primary diagnosed with astrocytoma WHO grade I and subsequently after four years developed a GBM, was detected with a mtDNA4977. This
deletion appears to be a sporadic mutation. Additionally, analysis of patient’s tumor tissue also found to harbor a heterozygous IDH1 R132H mutation. This represents the first case report of coexisting mtDNA4977 together with IDH1
R132H mutation in a Malaysian patient of GBM. The findings of dual alterations could be of therapeutic benefit if
these alterations were justified to be contributing to GBM growth and aggressiveness.

Matched MeSH terms: Mutation

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