Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 6 de 6
Filter
1.
J Pediatr Hematol Oncol ; 43(2): e198-e202, 2021 03 01.
Article in English | MEDLINE | ID: mdl-31815888

ABSTRACT

Constitutional mismatch repair deficiency (CMMRD) is an autosomal recessively inherited childhood cancer predisposition syndrome results from biallelic germline mutations affecting the key DNA mismatch repair gene: MLH1, MSH2, MSH6, or PMS2. CMMRD is associated with a high risk of developing early onset of central nervous system tumors, hematologic, and intestinal tract tumors. Clinical manifestations, genetic screening, and cancer prevention strategies are limited. In this report we present a patient with metachronous Wilms tumor, glioblastoma, and acute T-cell lymphoblastic leukemia. He had cutaneous features of neurofibromatosis type 1 (NF1). Molecular testing revealed a novel homozygous mutation in MSH6 (c.2590G>T; p.G864*) that has not been reported previously. CMMRD should be considered in patients with cutaneous features similar to NF1 if tumor is found other than expected tumors in NF, early onset cancer, and strong family history of cancer.


Subject(s)
Brain Neoplasms/complications , Colorectal Neoplasms/complications , DNA-Binding Proteins/genetics , Glioblastoma/pathology , Leukemia, T-Cell/pathology , Mutation , Neoplasms, Second Primary/pathology , Neoplastic Syndromes, Hereditary/complications , Wilms Tumor/pathology , Brain Neoplasms/genetics , Child, Preschool , Colorectal Neoplasms/genetics , Fatal Outcome , Glioblastoma/etiology , Homozygote , Humans , Kidney Neoplasms/etiology , Kidney Neoplasms/pathology , Leukemia, T-Cell/etiology , Male , Neoplasms, Second Primary/etiology , Neoplastic Syndromes, Hereditary/genetics , Wilms Tumor/etiology
3.
J Pediatr Neurosci ; 13(2): 205-207, 2018.
Article in English | MEDLINE | ID: mdl-30090137

ABSTRACT

Leigh syndrome (LS) is a progressive neurodegenerative disease caused by either mitochondrial or nuclear DNA mutations resulting in dysfunctional mitochondrial energy metabolism. The onset of clinical features is typically between 3 and 12 months of age; however, a later onset has been described in a few patients. Complex I deficiency is reported to be the most common cause of mitochondrial disorders. We described a patient with a late-onset LS, who presented with gait ataxia, caused by complex I deficiency (NDUFV1 gene).

4.
Am J Med Genet A ; 167A(11): 2795-9, 2015 Nov.
Article in English | MEDLINE | ID: mdl-26238661

ABSTRACT

Klippel-Feil syndrome is a rare disorder represented by a subgroup of segmentation defects of the vertebrae and characterized by fusion of the cervical vertebrae, low posterior hairline, and short neck with limited motion. Both autosomal dominant and recessive inheritance patterns were reported in families with Klippel-Feil. Mutated genes for both dominant (GDF6 and GDF3) and recessive (MEOX1) forms of Klippel-Feil syndrome have been shown to be involved in somite development via transcription regulation and signaling pathways. Heterotaxy arises from defects in proteins that function in the development of left-right asymmetry of the developing embryo. We describe a consanguineous family with a male proband who presents with classical Klippel-Feil syndrome together with heterotaxy (situs inversus totalis). The present patient also had Sprengel's deformity, deformity of the sternum, and a solitary kidney. Using exome sequencing, we identified a homozygous frameshift mutation (c.299delT; p.L100fs) in RIPPLY2, a gene shown to play a crucial role in somitogenesis and participate in the Notch signaling pathway via negatively regulating Tbx6. Our data confirm RIPPLY2 as a novel gene for autosomal recessive Klippel-Feil syndrome, and in addition-from a mechanistic standpoint-suggest the possibility that mutations in RIPPLY2 could also lead to heterotaxy. © 2015 Wiley Periodicals, Inc.


Subject(s)
Klippel-Feil Syndrome/genetics , Mutation/genetics , Receptors, Notch/genetics , Signal Transduction/genetics , Adolescent , Base Sequence , Female , Humans , Klippel-Feil Syndrome/diagnostic imaging , Male , Molecular Sequence Data , Pedigree , Radiography , Spine/diagnostic imaging
5.
Coron Artery Dis ; 24(3): 196-200, 2013 May.
Article in English | MEDLINE | ID: mdl-23283030

ABSTRACT

BACKGROUND: We aimed to examine the association between plasminogen activator inhibitor-1 (PAI-1) genetic polymorphism and early spontaneous recanalization in patients presenting with acute ST-elevation myocardial infarction. METHODS: Patients admitted to our emergency department with ST-elevation myocardial infarction in the first 6 h of symptom onset were included. An immediate primary percutaneous coronary intervention was performed. Patients were grouped according to the initial patency of the infarct-related artery (IRA) as follows: total occlusion (TO) group [Thrombolysis in Myocardial Infarction (TIMI) 0-1 flow in the IRA], partial recanalization group (TIMI 2 flow in the IRA), and complete recanalization (CR) group (TIMI 3 flow in the IRA). PAI-1 4G/5G polymorphism was detected using the real-time PCR method. RESULTS: There were 107 patients in the TO group, 30 patients in the partial recanalization group, and 45 patients in the CR group. When we evaluated degrees of patency according to the PAI-1 genotype, TO of the IRA was the highest in patients with the PAI 4G/4G genotype (PAI-1 4G/4G: 66.7%, PAI-1 4G/5G: 65.9%, PAI-1 5G/5G: 40.4%) and CR of the IRA was the highest in patients with the PAI 5G/5G genotype (PAI-1 5G/5G: 38.5%, PAI-1 4G/5G: 19.8%, PAI-1 4G/4G: 17.9%). The distribution of genotypes in different degrees of patency of IRA was statistically significant (P=0.029). In logistic regression analysis, the PAI-1 5G/5G genotype was associated independently with the spontaneous CR of the IRA (odds ratio: 2.875, 95% confidence interval [1.059-7.086], P=0.038). CONCLUSION: Patients with the PAI-1 5G/5G genotype seem to be luckier than others in terms of early spontaneous recanalization of the IRA. Further prospective studies with large patient populations are required for more precise results.


Subject(s)
Coronary Occlusion/genetics , Coronary Vessels/physiopathology , Myocardial Infarction/genetics , Plasminogen Activator Inhibitor 1/genetics , Polymorphism, Genetic , Vascular Patency/genetics , Adult , Aged , Chi-Square Distribution , Coronary Angiography , Coronary Occlusion/complications , Coronary Occlusion/diagnostic imaging , Coronary Occlusion/physiopathology , Coronary Occlusion/therapy , Coronary Vessels/diagnostic imaging , Electrocardiography , Female , Gene Frequency , Genetic Predisposition to Disease , Humans , Logistic Models , Male , Middle Aged , Myocardial Infarction/diagnostic imaging , Myocardial Infarction/physiopathology , Myocardial Infarction/therapy , Odds Ratio , Percutaneous Coronary Intervention , Phenotype , Prognosis , Real-Time Polymerase Chain Reaction , Risk Factors , Severity of Illness Index
6.
Coron Artery Dis ; 23(6): 400-3, 2012 Sep.
Article in English | MEDLINE | ID: mdl-22850480

ABSTRACT

BACKGROUND: In this study, we examined the relationship between PAI-1 4G/5G polymorphism and patency of the infarct-related artery after thrombolysis in patients with ST-elevation myocardial infarction (STEMI). METHODS: Acute STEMI patients who received thrombolytic therapy within first 12 h were included in our study. The PAI-1 4G/5G promoter region insertion/deletion polymorphism was studied from venous blood samples. Patients with the PAI-1 4G/5G gene polymorphism were included in group 1 and the others were included in group 2. Coronary angiography was performed in all patients in the first 24 h after receiving thrombolytic therapy. Thrombolysis in myocardial infarction (TIMI) 0-1 flow in the infarct-related artery was considered as 'no flow', TIMI 2 flow as 'slow flow', and TIMI 3 flow as 'normal flow'. RESULTS: A total of 61 patients were included in our study. Thirty patients (49.2%) were positive for the PAI-1 4G/5G gene polymorphism, whereas 31 of them (50.8%) were in the control group. There were significantly more patients with 'no flow' (14 vs. 6; P=0.02) and less patients with 'normal flow' (8 vs. 19; P=0.02) in group 1. In addition, time to thrombolytic therapy (TTT) was maximum in the 'no flow' group and minimum in the 'normal flow' group (P=0.005). In the logistic regression analysis, TTT (odds ratio: 0.9898; 95% confidence interval: 0.982-0.997; P=0.004) and the PAI-1 4G/5G gene polymorphism (odds ratio: 4.621; 95% confidence interval: 1.399-15.268; P<0.01) were found to be independently associated with post-thrombolytic 'no flow'. CONCLUSION: The PAI-1 4G/5G gene polymorphism and TTT are associated independently with 'no flow' after thrombolysis in patients with STEMI.


Subject(s)
Coronary Vessels/pathology , Myocardial Infarction/genetics , Plasminogen Activator Inhibitor 1/genetics , Aged , Coronary Angiography , Female , Fibrinolytic Agents/therapeutic use , Gene Frequency , Genotype , Humans , Male , Middle Aged , Myocardial Infarction/drug therapy , Myocardial Infarction/pathology , Polymorphism, Genetic , Risk Factors , Streptokinase/therapeutic use , Thrombolytic Therapy/methods , Tissue Plasminogen Activator/therapeutic use , Treatment Outcome
SELECTION OF CITATIONS
SEARCH DETAIL
...