Objective: To detect of gene expression and genotype of the ataxia telangiectasia mutated (ATM) from coal workers' pneumoconiosis (CWP) , It is explored whether CWP is related to ATM gene. Methods: In October 2020, the relevant information of 264 subjects who received physical examination or medical treatment in the Department of occupational diseases of Guiyang public health treatment center from January 2019 to September 2020 was collected. Through the occupational health examination, 67 healthy people with no history of exposure to occupational hazards were selected as the healthy control group; The coal miners with more than 10 years of coal dust exposure history and small shadow in the lung but not up to the diagnostic criteria were the dust exposure control group, a total of 66 people; The patients with the same history of coal dust exposure and confirmed stage I were coal worker's pneumoconiosis stage I group, a total of 131 people. The expression of ATM was detected by QRT PCR. ATM rs189037 and rs1801516 were genotyped by massarray. Results: There was significant difference in the expression of ATM among the groups (P<0.05) ; Compared with the healthy control group, the expression of ATM in the dust exposed control group was significantly increased (P<0.05) . With the occurrence and development of CWP, the GG of rs189037 wild type decreased, the GA of mutant heterozygote and AA of homozygote increased, but the difference was not statistically significant (P>0.05) ; Rs1801516 wild type GG and mutant heterozygote GA had no significant changes (P>0.05) . There were significant differences in age, neutrophils and basophils among rs189037 groups (all P<0.05) . There were no significant differences in blood pressure, eosinophils, lymphocytes, monocytes, smoking and drinking history among rs189037 groups (all P>0.05) . Compared with wild-type GG, the or of mutant heterozygotes and homozygotes increased, but the differences were not statistically significant (P>0.05) . Conclusion: ATM gene may be one of the early activation genes of CWP and rs189037 may be the functional loci which affects gene expression. ATM gene is related to inflammatory response, Neutrophils and basophils have an impact on the development of CWP.
Anthracosis/genetics* ; Ataxia Telangiectasia ; Ataxia Telangiectasia Mutated Proteins/genetics* ; China ; Coal ; Coal Mining ; Humans ; Miners ; Pneumoconiosis/epidemiology* ; Polymorphism, Single Nucleotide

Cardiovascular disease is a severe threat to human health and life. Among many risk factors of cardiovascular disease, genetic or gene-based ones are drawing more and more attention in recent years. Accumulated evidence has demonstrated that the loss or mutation of ataxia telangiectasia mutated (ATM) gene can result in DNA damage repair dysfunctions, telomere shortening, decreased antioxidant capacity, insulin resistance, increased lipid levels, etc., and thus can promote the occurrence of cardiovascular risk factors, such as aging, atherosclerosis and metabolic syndrome. In this review, we discusses the possible mechanisms between ATM gene and cardiovascular risk factors, which could be helpful to the related research and clinical application.
Aging ; Ataxia Telangiectasia Mutated Proteins ; genetics ; Cardiovascular Diseases ; genetics ; DNA Damage ; DNA Repair ; Humans ; Mutation ; Risk Factors

OBJECTIVE: Two brothes with Seckel's syndrome 1(SCKL1) were reported and a literature review was carried to provide clinical and genetic information of this rare disease. METHODS: Clinical data of the two children were collected, and the peripheral blood was extracted for whole exome sequencing. Literature of the disease were reviewed. RESULTS: The two patients were 11 years and 9.5 years old when examined for short stature. They presented with intrauterine growth retardation, intellectual disability, microcephaly, birdhead-like face and coffee au lait spots. The bone age was more than 2 years behind the chronical age and the growth hormone levels were normal. Whole exome sequencing revealed novel compound heterozygous variants c.1A>G (p.M1?) and c.4853-18A>G of ART gene in both children. CONCLUSION Children with prenatal onset short stature, developmental delay, microcephaly and special facial featuresshould be considered for the possibility of Seckel's syndrome, whole exome sequencing could help to confirm the clinical diagnosis.
Ataxia Telangiectasia Mutated Proteins/genetics* ; Child ; Dwarfism/genetics* ; Humans ; Intellectual Disability/genetics* ; Male ; Microcephaly/genetics* ; Siblings ; Whole Exome Sequencing

The mutation of AT gene (ATM) leads to the AT disease (ataxia telangiectasis), the cancer incidence of AT patients and its carriers are significantly higher than the normal persons. And they are easy to have lymphoid tumors, including the lymphoma and leukemia et al. These indicate the ATM play a important role in the cancers pathogenesis mechanism. The ATM gene locate in the human chromosome 11q22-23, and the ATM is a kind of nuclear protein, its major functional domain is P13K (phosphatidylinositol 3-kinase), locates on the carboxy terminus. ATM protein plays a critical role in the signal transduction of cell cycle checkpoint, the repair of damaged DNA and the apoptosis. The mutation of the ATM gene leads to the functional and structural change of ATM protein in the AT patient, then leads to the abnormality of cell cycle checkpoint and the DNA damage repair, the apoptosis sensitivity increase. So the AT patients and their cells are radiosensitive, the characteristic of AT patient suggests the ATM gene is valuable in the cancer's gene therapy
Ataxia Telangiectasia ; complications ; Ataxia Telangiectasia Mutated Proteins ; Cell Cycle Proteins ; DNA-Binding Proteins ; Genetic Predisposition to Disease ; Humans ; Leukemia ; epidemiology ; etiology ; genetics ; Lymphoma ; epidemiology ; etiology ; genetics ; Protein-Serine-Threonine Kinases ; genetics ; Signal Transduction ; Tumor Suppressor Proteins

Semen cryopreservation is an important method in assisted reproductive technology, but meanwhile it is complicated by cryodamage to spermatozoa. Mechanisms behind the cryodamage to spermatozoa are thought to be multifactorial, and the excessive generation of reactive oxygen species (ROS) has been suggested as a major contributing factor. DNA-damaged sperm is also capable of fertilizing oocytes, significantly affecting the outcome of reproduction. As a sensor of DNA damage responses, protein kinase ATM (ataxia telangiectasia mutated) can be initiated through rapid intermolecular autophosphorylation induced by DNA damage, phosphorylate various proteins, and amplify the responses to DNA damage. After DNA damage, histone H2AX is activated by ATM, which contributes to the repair of sperm-DNA damage after fertilization and regulates the cell cycle during embryo development. Given the important role of the ATM/H2AX signaling pathway in the response to and repair of DNA damage induced by oxidative stress, it may mediate the repair of sperm-DNA damage resulting from cryopreservation.
Animals ; Ataxia Telangiectasia Mutated Proteins ; Cell Cycle Proteins ; Cryopreservation ; DNA Damage ; DNA-Binding Proteins ; Histones ; Male ; Protein-Serine-Threonine Kinases ; Spermatozoa ; Tumor Suppressor Proteins

Ataxia-telangiectasia (A-T) is a rare autosomal recessive neurodegenerative disorder. It is characterized by early-onset, progressive cerebellar ataxia, oculomotor apraxia, choreoathetosis, conjunctival telangiectasias, immunodeficiency, and an increased risk of malignancy. Although A-T is known to be the most common cause of progressive cerebellar ataxia in childhood, there have been no confirmed cases in Korea. We report the clinical and genetic findings of Korean siblings who presented with limb and truncal ataxia, oculomotor apraxia, choreoathetosis, and telangiectasias of the eyes. Sequence analysis of the ataxia-telangiectasia mutated (ATM) gene revealed a known missense mutation (c.8546G>C; p.Arg2849Pro) and a novel intronic variant of intron 17 (c.2639-19_2639-7del13). Reverse-transcription PCR and sequencing analysis revealed that the c.2639-19_2639-7del13 variant causes a splicing aberration that potentiates skipping exon 18. Because A-T is quite rare in Korea, the diagnosis of A-T in Korean patients can be delayed. We recommend that a diagnosis of A-T should be suspected in Korean patients exhibiting the clinical features of A-T.
Asian Continental Ancestry Group/*genetics ; Ataxia Telangiectasia/diagnosis/*genetics ; Ataxia Telangiectasia Mutated Proteins/*genetics ; Child ; Female ; Heterozygote ; Humans ; Introns ; Male ; Mutation, Missense ; Pedigree ; Republic of Korea ; Reverse Transcriptase Polymerase Chain Reaction ; Sequence Analysis, DNA ; Siblings

Ataxia-telangiectasia (A-T) is a rare autosomal recessive neurodegenerative disorder. It is characterized by early-onset, progressive cerebellar ataxia, oculomotor apraxia, choreoathetosis, conjunctival telangiectasias, immunodeficiency, and an increased risk of malignancy. Although A-T is known to be the most common cause of progressive cerebellar ataxia in childhood, there have been no confirmed cases in Korea. We report the clinical and genetic findings of Korean siblings who presented with limb and truncal ataxia, oculomotor apraxia, choreoathetosis, and telangiectasias of the eyes. Sequence analysis of the ataxia-telangiectasia mutated (ATM) gene revealed a known missense mutation (c.8546G>C; p.Arg2849Pro) and a novel intronic variant of intron 17 (c.2639-19_2639-7del13). Reverse-transcription PCR and sequencing analysis revealed that the c.2639-19_2639-7del13 variant causes a splicing aberration that potentiates skipping exon 18. Because A-T is quite rare in Korea, the diagnosis of A-T in Korean patients can be delayed. We recommend that a diagnosis of A-T should be suspected in Korean patients exhibiting the clinical features of A-T.
Asian Continental Ancestry Group/*genetics ; Ataxia Telangiectasia/diagnosis/*genetics ; Ataxia Telangiectasia Mutated Proteins/*genetics ; Child ; Female ; Heterozygote ; Humans ; Introns ; Male ; Mutation, Missense ; Pedigree ; Republic of Korea ; Reverse Transcriptase Polymerase Chain Reaction ; Sequence Analysis, DNA ; Siblings

No abstract available.
Adolescent ; Ataxia Telangiectasia/*genetics ; Ataxia Telangiectasia Mutated Proteins/*genetics ; Base Sequence ; Chromosome Inversion ; Chromosomes, Human, Pair 14/genetics ; Chromosomes, Human, Pair 7/genetics ; DNA Mutational Analysis ; Female ; Humans ; Karyotyping ; Magnetic Resonance Imaging ; Mutation ; RNA Splicing ; Translocation, Genetic

OBJECTIVETo investigate miR-181a function and regulation mechanism by identifying miR-181a target genes in acute myeloid leukemia (AML).

METHODSThe HL-60 cells of human AML was transfected by small molecular analog miR-181a, the cell proliferation was detected by CCK-8 method after electroporation in HL-60 cell lines. Target genes of miR-181a were predicted and analyzed by the bioinformatics software and database. Target genes were confirmed by HL-60 cell line and the patient leukemia cells.

RESULTSOverexpressed miR-181a in HL-60 cell line significantly enhanced cell proliferation compared with that in control (P < 0.05). Dual luciferase reporter gene assay showed that miR-181a significantly suppressed the reporter gene activity containing ATM 3'-UTR by about 56.8% (P < 0.05), but it didn't suppress the reporter gene activity containing 3'-UTR ATM mutation. Western blot showed that miR-181a significantly downregulated the expression of ATM in human leukemia cells. It is also found that miR-181a was significantly increased in AML, which showed a negative correlation with ATM expression.

CONCLUSIONmiR-181a promotes cell proliferation in AML by regulating the tumor suppressor ATM, thus it plays the role as oncogene in pathogenesis of AML.

Ataxia Telangiectasia Mutated Proteins ; metabolism ; Cell Proliferation ; Down-Regulation ; HL-60 Cells ; Humans ; Leukemia, Myeloid, Acute ; metabolism ; pathology ; MicroRNAs ; genetics ; metabolism ; Transfection

OBJECTIVE: To explore the clinical characteristics and genetic basis of two brothers featuring X-linked alpha thalassemia mental retardation (ATR-X) syndrome. METHODS: An infant who had presented at the Qilu Children's Hospital in 2020 for unstable upright head and inability to roll over and his family were selected as the study subjects. The clinical features of the child and one of his brothers were summarized, and their genomic DNA was subjected to targeted capture and next generation sequencing (NGS). RESULTS: The brothers had presented with mental retardation and facial dysmorphisms. NGS revealed that they had both harbored a hemizygous c.5275C>A variant of the ATRX gene located on the X chromosome, which was inherited from their mother. CONCLUSION The siblings were diagnosed with ATR-X syndrome. The discovery of the c.5275C>A variant has enriched the mutational spectrum of the ATRX gene.
Humans ; Infant ; Male ; alpha-Thalassemia/diagnosis* ; Ataxia Telangiectasia Mutated Proteins/genetics* ; East Asian People ; Intellectual Disability/genetics* ; Mental Retardation, X-Linked/diagnosis* ; Pedigree ; X-linked Nuclear Protein/genetics*