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1.
J Med Virol ; 95(2): e28457, 2023 02.
Article in English | MEDLINE | ID: mdl-36597901

ABSTRACT

Thrombotic and microangiopathic effects have been reported in COVID-19 patients. This study examined the contribution of the hereditary thrombophilia factors Prothrombin (FII) and Factor V Leiden (FVL) genotypes to the severity of COVID-19 disease and the development of thrombosis. This study investigated FII and FVL alleles in a cohort of 9508 patients (2606 male and 6902 female) with thrombophilia. It was observed that 930 of these patients had been infected by SARS-CoV-2 causing COVID-19. The demographic characteristics of the patients and their COVID-19 medical history were recorded. Detailed clinical manifestations were analyzed in a group of cases (n = 4092). This subgroup was age and gender-matched. FII and FVL frequency data of healthy populations without thrombophilia risk were obtained from Bursa Uludag University Medical Genetic Department's Exome Databank. The ratio of males (31.08%; 27.01%) and the mean age (36.85 ± 15.20; 33.89 ± 14.14) were higher among COVID-19 patients compared to non-COVID-19 patients. The prevalence of FVL and computerized tomography (CT) positivity in COVID-19 patients was statistically significant in the thrombotic subgroup (p < 0.05). FVL prevalence, CT positivity rate, history of thrombosis, and pulmonary thromboembolism complication were found to be higher in deceased COVID-19 patients (p < 0.05). Disease severity was mainly affected by FVL and not related to genotypes at the Prothrombin mutations. Overall, disease severity and development of thrombosis in COVID-19 are mainly affected by the variation within the FVL gene. Possible FVL mutation should be investigated in COVID-19 patients and appropriate treatment should be started earlier in FVL-positive patients.


Subject(s)
COVID-19 , Thrombophilia , Thrombosis , Humans , Male , Female , Prothrombin/genetics , Risk Factors , SARS-CoV-2 , Genotype , Factor V/genetics , Thrombophilia/epidemiology , Thrombophilia/genetics , Patient Acuity , Mutation
2.
Turk J Med Sci ; 52(5): 1458-1467, 2022 Oct.
Article in English | MEDLINE | ID: mdl-36422510

ABSTRACT

BACKGROUND: NLRP3 inflammasome activation has been known to be involved in the etiology and progression of Alzheimer's disease (AD). Furthermore, AD and diabetes mellitus have common pathomechanisms. It has been shown that P2X7R whose expression is increased in brain tissues with AD and plays a role in the activation of NLRP3 inflammasome is suppressed by miR-373 in patients with osteoarthritis. Therefore, the question of whether the suppressive effect of miR-373 on NLRP3 may have a role in the pathophysiology of AD comes to mind. On the other hand, it is known that the miR-204 level increases in response to TXNIP, another NLRP3 inflammasome inducer with high expression in AD. In primary human islets, miR-204 reduces the expression of GLP-1R. It has been discovered that in vivo deletion of miR-204 is protective against diabetes by increasing GLP-1R and insulin secretion. Considering the relationship between miR-204 and TXNIP and the relationship of miR-204 with diabetes suggests investigating the effect of miR-204 on the inflammatory pathway in AD. Based on the common pathophysiological mechanisms between AD and diabetes and the reported changes related to NLRP3 inflammasome, we analyzed miR-373 and miR-204 in neuron-derived serum exosomes in this study. Neuron-derived exosomes in neurodegenerative diseases are considered to be better candidates for developing potential biomarkers. METHODS: The expression levels of miR-204 and miR-373 were investigated in neuron-derived serum exosomes obtained from 15 patients with mild AD, 18 with moderate AD, and 21 cognitively healthy individuals. RESULTS: The miR-204 and miR-373 expressions were significantly decreased in both patient groups compared to the control group. Therefore, we suggest that miR-204 and miR-373 are potential biomarkers for AD. However, due to the preliminary nature of this study, further large-scale studies are needed to support our findings.


Subject(s)
Alzheimer Disease , Exosomes , MicroRNAs , Humans , Inflammasomes/metabolism , Exosomes/genetics , Exosomes/metabolism , Alzheimer Disease/genetics , NLR Family, Pyrin Domain-Containing 3 Protein/genetics , NLR Family, Pyrin Domain-Containing 3 Protein/metabolism , MicroRNAs/genetics , MicroRNAs/metabolism , Neurons , Biomarkers
3.
Am J Med Genet A ; 188(7): 2153-2161, 2022 07.
Article in English | MEDLINE | ID: mdl-35332675

ABSTRACT

Hereditary sensory and autonomic neuropathy type 2B (HSAN2B) is a rare autosomal recessive peripheral neuropathy caused by biallelic variants in RETREG1 (formerly FAM134B). HSAN2B is characterized by sensory impairment resulting in skin ulcerations, amputations, and osteomyelitis as well as variable weakness, spasticity, and autonomic dysfunction. Here, we report four affected individuals with recurrent osteomyelitis, ulceration, and amputation of hands and feet, sensory neuropathy, hyperhidrosis, urinary incontinence, and renal failure from a family without any known shared parental ancestry. Due to the history of chronic recurrent multifocal osteomyelitis and microcytic anemia, a diagnosis of Majeed syndrome was considered; however, sequencing of LPIN2 was negative. Family-based exome sequencing (ES) revealed a novel homozygous ultrarare RETREG1 variant NM_001034850.2:c.321G>A;p.Trp107Ter. Electrophysiological studies of the proband demonstrated axonal sensorimotor neuropathy predominantly in the lower extremities. Consistent with the lack of shared ancestry, the coefficient of inbreeding calculated from ES data was low (F = 0.002), but absence of heterozygosity (AOH) analysis demonstrated a 7.2 Mb AOH block surrounding the variant consistent with a founder allele. Two of the four affected individuals had unexplained renal failure which has not been reported in HSAN2B cases to date. Therefore, this report describes a novel RETREG1 founder allele and suggests renal failure may be an unrecognized feature of the RETREG1-disease spectrum.


Subject(s)
Hereditary Sensory and Autonomic Neuropathies , Intracellular Signaling Peptides and Proteins , Membrane Proteins , Osteomyelitis , Renal Insufficiency , Alleles , Humans , Intracellular Signaling Peptides and Proteins/genetics , Membrane Proteins/genetics , Osteomyelitis/genetics , Pedigree
4.
Cytogenet Genome Res ; 160(9): 523-530, 2020.
Article in English | MEDLINE | ID: mdl-33161406

ABSTRACT

Sterol-C4-methyl oxidase (SC4MOL) deficiency was recently described as an autosomal recessive cholesterol biosynthesis disorder caused by mutations in the MSMO1 (sometimes also referred to as SC4MOL) gene. To date, 5 patients from 4 unrelated families with SC4MOL deficiency have been reported. Diagnosis can be challenging as the biochemical accumulation of methylsterols can affect global development and cause skin and ocular pathology. Herein, we describe 2 siblings from a consanguineous Turkish family with SC4MOL deficiency presenting with psoriasiform dermatitis, ocular abnormalities (nystagmus, optic hypoplasia, myopia, and strabismus), severe intellectual disability, and growth and motor delay. We undertook whole-exome sequencing and identified a new homozygous missense mutation c.81A>C; p.Asn27Thr in MSMO1. Segregation analysis in all available family members confirmed recessive inheritance of the mutation. The siblings were treated with a combination of oral and topical statin and cholesterol which resulted in clinical improvement. This study demonstrates how genomics-based diagnosis and therapy can be helpful in clinical practice.


Subject(s)
Dermatitis/genetics , Mixed Function Oxygenases/genetics , Mutation, Missense , Psoriasis/genetics , Child , Cholesterol/biosynthesis , Cholesterol/blood , Cholesterol/deficiency , Cholesterol/therapeutic use , Consanguinity , Eye Diseases/genetics , Female , Genes, Recessive , Growth Disorders/genetics , Homozygote , Humans , Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use , Intellectual Disability/genetics , Male , Mixed Function Oxygenases/deficiency , Pedigree , Rosuvastatin Calcium/therapeutic use , Siblings , Triglycerides/blood , Turkey , Exome Sequencing
5.
Int J Hematol ; 104(3): 368-77, 2016 Sep.
Article in English | MEDLINE | ID: mdl-27393278

ABSTRACT

The ETV6/RUNX1 fusion gene is a valuable prognostic marker that is frequently observed in B-cell precursor acute lymphoblastic leukemia (B-cell ALL). However, the clinical significance of copy number aberrations in these genes remains unclear. In this study, the effects of various aberrations inETV6 and RUNX1 gene copy number on disease prognosis were evaluated in 21 pediatric patients diagnosed with B-cell ALL with/without t(12;21). The prognostic significance of changes in gene copy number of ETV6 or RUNX1 in the presence or absence of hyperdiploidy, trisomy 21, and t(12;21) translocation were also evaluated. RUNX1 gene copy number amplifications were detected in 83 % of the patients who lacked t(12;21) and in all of the patients with hyperdiploidy. Trisomy 21 was detected in 78 % of the patients with hyperdiploidy. Changes in ETV6 gene copy number were detected in patients who lacked both the t(12;21) translocation and RUNX1 gene copy number amplifications. However, RUNX1 gene copy number amplification and ETV6 deletion were observed in all of the patients with t(12;21). RUNX1 gene copy number amplification was associated with hyperdiploidy, but not with t(12;21). Thus, the evaluation of distinct FISH and cytogenetic patterns in patients with B-cell ALL may strengthen the prognostic significance of changes in gene copy number.


Subject(s)
Core Binding Factor Alpha 2 Subunit/genetics , Diploidy , Gene Dosage , Precursor B-Cell Lymphoblastic Leukemia-Lymphoma/diagnosis , Proto-Oncogene Proteins c-ets/genetics , Repressor Proteins/genetics , Child , Child, Preschool , Humans , In Situ Hybridization, Fluorescence , Precursor B-Cell Lymphoblastic Leukemia-Lymphoma/genetics , Prognosis , ETS Translocation Variant 6 Protein
6.
Ann Hematol ; 89(4): 359-64, 2010 Apr.
Article in English | MEDLINE | ID: mdl-19798502

ABSTRACT

The aim of this study was to describe the characteristics and outcome in a group of pediatric patients with hematological malignancies who developed hemophagocytosis at diagnosis or during the disease course. Eight patients with hematological malignancy and associated hemophagocytosis were included. The initial diagnosis was juvenile myelomonocytic leukemia (JMML) in five, nonlymphoblastic leukemia (ANLL) in two, and T-cell lymphoma associated with myeloproliferative syndrome in one patient. Hemophagocytosis was concomitantly present at the time of diagnosis of the primary disease in four of the five patients with JMML and in the two patients with ANLL. Three had abnormalities related to chromosome 8 [(trisomy 8, monosomy 8, and t (8;13) (p11; p12)], and one had inversion 16. Multiple chromosomal losses were present in one patient, including both chromosomes 8 and 16. Bone marrow karyotyping revealed 46, XX; 47, XXX mosaicism in one patient. Two patients had PTPN11 mutation and one patient k-RAS mutation. The patients with JMML and neurofibromatosis (n = 2), the patient with lymphoma and t (8;13) positive AML, and a fourth patient with PTPN11 mutation did not remit and had unfavorable outcomes.


Subject(s)
Leukemia, Myelomonocytic, Juvenile/pathology , Phagocytosis , Adolescent , Antineoplastic Agents/therapeutic use , Child , Child, Preschool , Chromosome Aberrations , Female , Genes, ras , Humans , Infant , Leukemia, Myeloid, Acute/drug therapy , Leukemia, Myeloid, Acute/genetics , Leukemia, Myeloid, Acute/pathology , Leukemia, Myelomonocytic, Juvenile/drug therapy , Leukemia, Myelomonocytic, Juvenile/genetics , Lymphoma, T-Cell/complications , Lymphoma, T-Cell/drug therapy , Lymphoma, T-Cell/genetics , Lymphoma, T-Cell/pathology , Male , Mutation , Myeloproliferative Disorders/complications , Myeloproliferative Disorders/drug therapy , Myeloproliferative Disorders/genetics , Myeloproliferative Disorders/pathology , Protein Tyrosine Phosphatase, Non-Receptor Type 11/genetics , Treatment Outcome
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