Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 2.578
Filtrar
1.
Gene ; 715: 143991, 2019 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-31357023

RESUMO

BACKGROUND: Asthma is a complex disease with worldwide public health relevance, is related to environmental causes and a genetic predisposition. The chromosomal 17q12-21 locus has been consistently demonstrated to be associated with asthma risk. The effects of variants in the 17q12-21 locus on childhood asthma were first identified in a genome wide- association study. Since that time, those findings have been replicated in different populations but not in South American populations. OBJECTIVE: This study aimed to investigate the role of variants in the 17q12-21 locus on asthma in a sample of Brazilian children. METHODS: This was a cross-sectional study conducted on a cohort of 1247 children. These analyses used 50 Single Nucleotide Variants (SNVs) in the 17q12-21 locus were genotyped as part of a genome wide association study (GWAS). RESULTS: Four SNVs (rs4065275, rs12603332, rs73985228 and rs77777702) were associated with childhood asthma. The rs73985228 exhibited the strongest association across the different genetic models (OR, 95%CI 2.8, 1.44-3.21, p < 0.01). In an analysis that was stratified by atopy, two SNVs (rs73985228 and rs2715555) were found to be associated with atopic and non-atopic asthma. For the first time, we observed a significant interaction with seropositivity for the Varicella zoster virus (for rs4065275, p = 0.02, and for rs12603332, p = 0.04); i.e., the association was found in those who were seropositive but not in those who were seronegative for this virus. CONCLUSIONS: We confirmed the associations of variants in the 17q12-21 locus with atopic and non-atopic asthma and identified an interaction with seropositivity for the Varicella zoster virus.


Assuntos
Asma/genética , Cromossomos Humanos Par 17/genética , Predisposição Genética para Doença , Herpesvirus Humano 3 , Polimorfismo de Nucleotídeo Único , Infecção pelo Vírus da Varicela-Zoster/genética , Asma/virologia , Criança , Pré-Escolar , Estudos Transversais , Feminino , Loci Gênicos , Estudo de Associação Genômica Ampla , Humanos , Masculino
2.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 36(7): 724-726, 2019 Jul 10.
Artigo em Chinês | MEDLINE | ID: mdl-31302921

RESUMO

OBJECTIVE: To explore the molecular mechanism of a girl with developmental delay and intellectual disability. METHODS: Chromosomal karotypes of the child and her parents were analyzed with routine G-banding method. Their genomic DNA was also analyzed with array comparative genomic hybridization (aCGH) for chromosomal duplications/deletions. RESULTS: No karyotypic abnormality was detected in the child and her parents, while aCGH has identified a de novo 3.37 Mb deletion at 17p11.2 in the child. CONCLUSION: The child was diagnosed with Smith-Magenis syndrome, for which RAI1 may be the causative gene.


Assuntos
Síndrome de Smith-Magenis/genética , Criança , Deleção Cromossômica , Duplicação Cromossômica , Cromossomos Humanos Par 17/genética , Hibridização Genômica Comparativa , Feminino , Humanos , Cariotipagem
3.
Anticancer Res ; 39(6): 2805-2810, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31177117

RESUMO

BACKGROUND/AIM: Galectins belong to the family of galactose-binding proteins known to play an important role in the processes of cell proliferation, differentiation, migration and neoplastic progression. Herein, we studied the expression of galectin-3 (Gal-3) in chronic lymphocytic leukemia (CLL). MATERIALS AND METHODS: The expression of Gal-3 was analyzed by means of multiparametric flow cytometry in normal and pathological B-cells from peripheral blood and bone marrow samples of 67 patients with CLL. RESULTS: Pathological B-cells expressed significantly higher levels of cytoplasmic Gal-3 than normal B-cells. Moreover, overexpression of cytoplasmic Gal-3 was observed in the prognostically poorest subgroup of CLL patients, namely those with 17p deletion. CONCLUSION: Our results indicate a possible role of galectin-3 in CLL pathophysiology and its potential value as a prognostic marker and therapeutic target.


Assuntos
Deleção Cromossômica , Cromossomos Humanos Par 17/genética , Galectina 3/genética , Leucemia Linfocítica Crônica de Células B/genética , Regulação para Cima , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/genética , Citoplasma/metabolismo , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico
4.
Cytogenet Genome Res ; 157(4): 227-230, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31030199

RESUMO

Miller-Dieker syndrome (MDS; OMIM 247200) is a rare contiguous gene deletion syndrome associated with lissencephaly and characteristic facial dysmorphism. T-cell lymphopenia is an immunodeficiency disorder which can be early detected by newborn blood screening, and all live vaccines should be avoided. We report a 2.32-Mb microdeletion at chromosome 17p13.3p13.2 and T-cell lymphopenia in a 6-month-old male infant with MDS. This is, to our knowledge, the first description of these 2 conditions co-occurring in the same patient.


Assuntos
Lissencefalias Clássicas e Heterotopias Subcorticais em Banda/diagnóstico , T-Linfocitopenia Idiopática CD4-Positiva/diagnóstico , Cromossomos Humanos Par 17/genética , Lissencefalias Clássicas e Heterotopias Subcorticais em Banda/genética , Comorbidade , Humanos , Hibridização in Situ Fluorescente , Lactente , Masculino , Deleção de Sequência , T-Linfocitopenia Idiopática CD4-Positiva/genética
5.
Ann Hematol ; 98(6): 1413-1420, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30830246

RESUMO

Acute promyelocytic leukemia (APL) is generally characterized by t(15;17)(q24;q21). In some cases, the classic translocation cannot be identified by conventional methods, since the PML-RARA fusion protein results from complex, variant, or cryptic translocation. The diagnostic algorithm of APL starts with screening methods, such as flow cytometry (FC), followed by fluorescence in situ hybridization or polymerase chain reaction to confirm the diagnosis. Our aim was to develop a novel protocol for analyzing APL samples based on multidimensional dot-plots that can provide comprehensive information about several markers at the same time. The protocol included four optimized multidimensional dot-plots, which were tested by retrospective reanalysis of FC results in APL (n = 8) and non-APL (n = 12) acute myeloid leukemia (AML) cases. After predicting the potential position of hypergranular- and microgranular-type aberrant promyelocytes, the percentages of blast populations were examined within the gates in all AML cases. The percentage of blasts in each predefined gate was well above the cut-off value (95%) in APL cases in all tubes. In non-APL AML cases, the percentage of blasts in the same gates never reached the cut-off value in all investigated tubes, and even when it did in a single tube, the pattern was markedly different from that observed in APL cases. In conclusion, multidimensional dot-plots can be used for screening APL even in cryptic APL cases, although reproducibility across several laboratories would require standardization of antibodies and fluorochromes. This easy-to-use and quick method can support the diagnosis of APL and the prompt initiation of the appropriate treatment.


Assuntos
Apresentação de Dados , Detecção Precoce de Câncer/métodos , Citometria de Fluxo/métodos , Imunofenotipagem/métodos , Leucemia Promielocítica Aguda/diagnóstico , Adulto , Idoso , Antígenos CD/análise , Antígenos de Neoplasias/análise , Biomarcadores Tumorais/análise , Medula Óssea/patologia , Bandeamento Cromossômico , Cromossomos Humanos Par 15/genética , Cromossomos Humanos Par 15/ultraestrutura , Cromossomos Humanos Par 17/genética , Cromossomos Humanos Par 17/ultraestrutura , Fator XIII/análise , Feminino , Citometria de Fluxo/instrumentação , Corantes Fluorescentes , Humanos , Imunofenotipagem/instrumentação , Hibridização in Situ Fluorescente , Leucemia Promielocítica Aguda/sangue , Leucemia Promielocítica Aguda/genética , Masculino , Pessoa de Meia-Idade , Células-Tronco Neoplásicas/patologia , Proteínas de Fusão Oncogênica/genética , Estudos Retrospectivos , Translocação Genética
6.
Nat Commun ; 10(1): 880, 2019 02 20.
Artigo em Inglês | MEDLINE | ID: mdl-30787307

RESUMO

Asthma is a complex disease with striking disparities across racial and ethnic groups. Despite its relatively high burden, representation of individuals of African ancestry in asthma genome-wide association studies (GWAS) has been inadequate, and true associations in these underrepresented minority groups have been inconclusive. We report the results of a genome-wide meta-analysis from the Consortium on Asthma among African Ancestry Populations (CAAPA; 7009 asthma cases, 7645 controls). We find strong evidence for association at four previously reported asthma loci whose discovery was driven largely by non-African populations, including the chromosome 17q12-q21 locus and the chr12q13 region, a novel (and not previously replicated) asthma locus recently identified by the Trans-National Asthma Genetic Consortium (TAGC). An additional seven loci reported by TAGC show marginal evidence for association in CAAPA. We also identify two novel loci (8p23 and 8q24) that may be specific to asthma risk in African ancestry populations.


Assuntos
Afro-Americanos/genética , Asma/genética , Predisposição Genética para Doença/genética , Asma/epidemiologia , Cromossomos Humanos Par 12/genética , Cromossomos Humanos Par 17/genética , Cromossomos Humanos Par 8/genética , Loci Gênicos , Estudo de Associação Genômica Ampla , Hispano-Americanos/genética , Humanos , Polimorfismo de Nucleotídeo Único/genética , Estados Unidos/epidemiologia
7.
Asian Pac J Cancer Prev ; 19(12): 3581-3589, 2018 Dec 25.
Artigo em Inglês | MEDLINE | ID: mdl-30583686

RESUMO

Objective: Triple negative breast cancer is an aggressive variant of breast cancer; it forms about 15% of breast cancer cases. It lacks the responsiveness to hormonal and targeted therapies. Anthracyclines remain the treatment option for these patients. Anthracyclines are cardiotoxic, so predicting sensitivity of response by biological predictors may have a role in selecting suitable candidates for these drugs. Material and methods: This study included 50 TNBC cases, from National Cancer Institute, Cairo University(NCI-CU), Egypt, who underwent surgery and received adjuvant chemotherapy. Archived blocks were obtained and immunostaining for Ki-67 LI and Fluorescent In situ Hybridization (FISH) technique to assess TOP2A gene copy number and chromosome 17CEP status were done. Analysis of association between TOP2A alterations and CEP17 polysomy as well as Ki-67 LI with other clinicopathological parameters was done. Associations between the biological markers and event free survival (EFS) and overall survival (OS), were also performed. Results: TOP2A alteration was seen in 9/50 cases (5 amplified and 4 deleted). CEP17 Polysomy was detected in 14% of cases. Most of patients (80%) showed Ki-67 LI ≥20%. There was a significant association between TOP2A gene and CEP17 status. Outcome was better with abnormal TOP2A gene status and CEP17 polysomy, radiotherapy and combined anthracyclines and taxanes in the adjuvant setting, however P-values were not significant. Conclusion: TOP2A gene alterations and CEP17 polysomy may have prognostic and predictive role in TNBC treated with adjuvant Anthracyclines.


Assuntos
Antraciclinas/uso terapêutico , DNA Topoisomerases Tipo II/genética , Proteínas de Ligação a Poli-ADP-Ribose/genética , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Neoplasias de Mama Triplo Negativas/genética , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Biomarcadores Tumorais/genética , Quimioterapia Adjuvante/métodos , Cromossomos Humanos Par 17/genética , Intervalo Livre de Doença , Egito , Feminino , Humanos , Antígeno Ki-67/genética , Pessoa de Meia-Idade , Polirribossomos/genética , Taxoides/uso terapêutico
8.
Ann Hematol ; 97(12): 2269-2278, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30315344

RESUMO

Chronic lymphocytic leukemia (CLL), a disorder for which B cell heterogeneity and increased cellular proliferation play central pathogenic roles, displays several genetic abnormalities that are associated with poor prognosis and have therapeutic implications. In this review, we discuss the prognostic role and therapeutic implications of chromosome 17p deletions and TP53 mutations in CLL. Unlike other recurrent genetic abnormalities, the frequency of TP53 alterations is relatively low in newly diagnosed patients, but increases sharply with disease progression, which suggests that these alterations represent an evolutionary mechanism of resistance. In comparison with patients without such abnormalities, those with 17p deletions and TP53 mutations have lower response rates and more aggressive disease. One important consequence of the diverse molecular mechanisms that affect the TP53 pathway is the need to assess both the presence of 17p deletion and TP53 mutations before treatment initiation. Several authors have attempted to incorporate TP53 abnormalities in different prognostic models for CLL, and the recent International Prognostic Index for Chronic Lymphocytic Leukemia formally considers patients with TP53 abnormalities (deletion 17p or TP53 mutation or both) as high-risk. Several novel agents may improve results in patients with CLL, including in those with TP53 mutations. Ibrutinib, idelalisib, and venetoclax have been approved in various settings and countries for treatment of CLL. Further progress in targeted therapy and judicious use of chemotherapy, monoclonal antibodies, and reduced-intensity allogeneic transplantation will provide patients with CLL in general, and those with TP53 abnormalities in particular, with a better prognosis.


Assuntos
Antineoplásicos/uso terapêutico , Deleção Cromossômica , Leucemia Linfocítica Crônica de Células B , Síndrome de Smith-Magenis , Transplante de Células-Tronco , Proteína Supressora de Tumor p53/genética , Aloenxertos , Cromossomos Humanos Par 17/genética , Humanos , Leucemia Linfocítica Crônica de Células B/diagnóstico , Leucemia Linfocítica Crônica de Células B/genética , Leucemia Linfocítica Crônica de Células B/terapia , Prognóstico , Síndrome de Smith-Magenis/diagnóstico , Síndrome de Smith-Magenis/genética , Síndrome de Smith-Magenis/terapia
9.
Bull Cancer ; 105(11): 1094-1101, 2018 Nov.
Artigo em Francês | MEDLINE | ID: mdl-30297237

RESUMO

Dematofibrosarcoma protuberans (DFSP) are very rare (1 to 4 incident cases per million of inhabitants). The local spreading of DFSP is underestimated. The histological diagnosis is challenging but we now know a specific marker (translocation t(17;22)(q22;q13) (COL1A1;PDGFB)). The risk of metastatic relapse is low (and related to fibrosarcoma component); the risk of local relapse depends on the quality of surgery. Management of localized DFSP is based on large resection with meticulous analysis of margins (with or without Mohs microsurgery). Advanced stages not amenable to surgery or metastatic DFSP (with presence of COL1A1;PDGFB) are best treated with imatinib. Locally advanced DFSP potentially amenable to curative intent surgery could be treated with imatinib as neo-adjuvant treatment. The management of these tumours requires multidisciplinary expertise.


Assuntos
Dermatofibrossarcoma , Doenças Raras , Neoplasias Cutâneas , Cromossomos Humanos Par 17/genética , Cromossomos Humanos Par 22/genética , Colágeno Tipo I/genética , Dermatofibrossarcoma/diagnóstico por imagem , Dermatofibrossarcoma/genética , Dermatofibrossarcoma/patologia , Dermatofibrossarcoma/terapia , Marcadores Genéticos , Humanos , Recidiva Local de Neoplasia , Proteínas Proto-Oncogênicas c-sis/genética , Doenças Raras/diagnóstico por imagem , Doenças Raras/genética , Doenças Raras/patologia , Doenças Raras/terapia , Neoplasias Cutâneas/diagnóstico por imagem , Neoplasias Cutâneas/genética , Neoplasias Cutâneas/patologia , Neoplasias Cutâneas/terapia , Translocação Genética
10.
Gene ; 678: 124-128, 2018 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-30096453

RESUMO

Chromosome 4q12 and 17q12 have been identified as two regions associated with susceptibility to cervical cancer in a genome-wide association study. To identify potential causal variants within these two regions, we conducted a case-control study including 1486 patients with cervical cancer and 1536 age-matched (±5 years) healthy controls. Based on RegulomeDB database, 12 potentially functional variants were selected and then genotyped by using Sequenom MassARRAY. Univariate and multivariate logistic regression models were used to evaluate the associations. We found that the G allele of rs8076131 and the A allele of rs12150079 in 17q12 region were significantly associated with increased risk of cervical cancer (adjusted OR = 1.15, 95% CI = 1.02-1.30, P = 0.02 for rs8076131; adjusted OR = 1.19, 95% CI = 1.03-1.36, P = 0.02 for rs12150079). Individuals with 3-4 risk alleles of these two variants had 24% higher odds of cervical cancer than those without the risk alleles (OR = 1.24, 95% CI = 1.07-1.44, P < 0.01). The stratified analysis showed that the associations of rs8076131 and rs12150079 with cervical cancer risk were statistically significant in subgroups of older menarche age (>16 years), more parities (≥2), nonsmokers, and having no family cancer history, but the test results for subgroup heterogeneity were not significant. The current study provides the evidence that rs8076131 and rs12150079 in 17q12 region may contribute to cervical cancer susceptibility in the Han Chinese population.


Assuntos
Grupo com Ancestrais do Continente Asiático/genética , Cromossomos Humanos Par 17/genética , Polimorfismo de Nucleotídeo Único , Análise de Sequência de DNA/métodos , Neoplasias do Colo do Útero/genética , Grupo com Ancestrais do Continente Asiático/etnologia , Estudos de Casos e Controles , Feminino , Estudos de Associação Genética , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Humanos , Estadiamento de Neoplasias
11.
Tohoku J Exp Med ; 245(3): 187-191, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-30012910

RESUMO

Campomelic dysplasia (CD) is a skeletal dysplasia characterized by shortened and bowed long bones, airway instability, the potential for disorders of sexual differentiation (DSD), and Pierre Robin Sequence (PRS) with cleft palate, midface hypoplasia and laryngotrachemomalacia. CD is caused by alterations in the Sex-determining region of the Y chromosome (SRY)-related-box 9 (SOX9), which has important roles in tissue and sexual differentiation. The SOX9 gene and the enhancer regions of SOX9 are located at chromosome 17q24.3. We report a 6-year-old phenotypically female referred to our department because of precocious puberty. The patient was born with Tetralogy of Fallot (TOF) and PRS. Skeletal X-ray examination showed only 11 pairs of ribs and bilateral bowed radiuses. Endocrine evaluations showed that increased levels of serum testosterone, and chromosomal analysis revealed a 46, XY, t(2;17)(p15;q24.2) karyotype. The patient was diagnosed with peripheral precocious puberty caused by over-secretion of testosterone by gonadoblastoma originating from dysgenetic gonads with Y-chromosome-related DSD. Multiple somatic abnormalities and DSD indicated that the patient might have CD. Laparoscopy revealed bilateral dysgenetic gonads, and these were removed in the successive operation to prevent malignant transformation and virilization, caused by dysgenetic gonads with Y chromosomal materials. It is highly suggestive that the chromosomal translocation of 17q 24.2 may cause DSD and multiple somatic abnormalities, including CD, although the identified 17q breakpoint was located outside of known SOX9 enhancer regions. Thus, a hitherto unknown enhancer may be present at 17q24.2. This is the first reported case of CD with a translocation breakpoint at 17q24.2.


Assuntos
Anormalidades Múltiplas/genética , Cromossomos Humanos Par 17/genética , Cromossomos Humanos Par 2/genética , Gônadas/anormalidades , Translocação Genética , Criança , Endoscopia , Feminino , Hormônios/sangue , Humanos
12.
Genes Genomics ; 40(5): 465-473, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29892954

RESUMO

Gender Dysphoria is characterized by a marked incongruence between the cerebral sex and biological sex. To investigate the possible influence of karyotype on the etiology of Gender Dysphoria we carried out the cytogenetic analysis of karyotypes in 444 male-to-females (MtFs) and 273 female-to-males (FtMs) that attended the Gender Identity Units of Barcelona and Málaga (Spain) between 2000 and 2016. The karyotypes from 23 subjects (18 MtFs and 5 FtMs) were also analysed by Affymetrix CytoScan™ high-density (HD) arrays. Our data showed a higher incidence of cytogenetic alterations in Gender Dysphoria (2.65%) than in the general population (0.53%) (p < 0.0001). When G-banding was performed, 11 MtFs (2.48%) and 8 FtMs (2.93%) showed a cytogenetic alteration. Specifically, Klinefelter syndrome frequency was significantly higher (1.13%) (p < 0.0001), however Turner syndrome was not represented in our sample (p < 0.61). At molecular level, HD microarray analysis revealed a 17q21.31 microduplication which encompasses the gene KANSL1 (MIM612452) in 5 out of 18 MtFs and 2 out of 5 FtMs that corresponds to a copy-number variation region in chromosome 17q21.31. In conclusion, we confirm a significantly high frequency of aneuploidy, specifically Klinefelter syndrome and we identified in 7 out of 23 GD individuals the same microduplication of 572 Kb which encompasses the KANSL1 gene.


Assuntos
Disforia de Gênero/etiologia , Disforia de Gênero/genética , Cariotipagem/métodos , Adulto , Bandeamento Cromossômico/métodos , Cromossomos Humanos Par 17/genética , Feminino , Identidade de Gênero , Duplicação Gênica/genética , Humanos , Cariótipo , Síndrome de Klinefelter , Masculino , Pessoa de Meia-Idade , Proteínas Nucleares/genética , Transexualismo/genética , Síndrome de Turner
13.
Mol Med Rep ; 18(1): 981-986, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29845227

RESUMO

The genetic basis of congenital mental retardation includes chromosomal anomalies and single gene mutations. In addition to chromosome microarray analysis, next­generation sequencing (NGS) and Sanger sequencing have additionally been applied to identify single gene mutations. However, no methods exist to identify the cause of an anomaly in one step. The present study applied an improved targeted NGS method to diagnose an 8­year­old Chinese Han female with mental retardation in one step. The microdeletion 17p11.2 was successfully detected by the improved targeted NGS and no single gene mutations were identified. The same microdeletion was verified using low coverage whole­genome sequencing. Fertility guidance was also given to the patient's parents. In the present study, an improved targeted NGS method was applied to diagnose non­syndromic mental retardation of unknown cause in one step. This improved method has the potential to be developed into a screening panel for the effective diagnosis of genetic abnormalities in non­syndromic mental retardation and other congenital anomalies.


Assuntos
Deleção Cromossômica , Sequenciamento de Nucleotídeos em Larga Escala , Deficiência Intelectual , Síndrome de Smith-Magenis , Criança , Cromossomos Humanos Par 17/genética , Feminino , Humanos , Deficiência Intelectual/diagnóstico , Deficiência Intelectual/genética , Síndrome de Smith-Magenis/diagnóstico , Síndrome de Smith-Magenis/genética
14.
Blood Cancer J ; 8(3): 28, 2018 03 07.
Artigo em Inglês | MEDLINE | ID: mdl-29515104

RESUMO

Clonal cytogenetic evolution (CE) (i.e., acquisition of new chromosomal aberrations over time) is relevant for the progression of myelodysplastic syndromes (MDS). We performed detailed analysis of CE in 729 patients with MDS and related disorders. Patients with CE showed shorter survival (median OS 18.0 versus 53.9 months; P < 0.01), higher leukemic transformation rate (48.0% versus 21.4%; P < 0.01) and shorter intervals to leukemic transformation (P < 0.01). Two main CE patterns were detected: early versus late CE (median onset 5.3 versus 21.9 months; P < 0.01) with worse survival outcomes for early CE. In the case of CE, del (7q)/-7 (P = 0.020) and del (17p) (P = 0.002) were especially unfavorable. Extending the evolution patterns from Tricot et al. (1985) forming five subgroups, prognosis was best (median OS not reached) in patients with "transient clones/changing clone size", whereas those with "CE at diagnosis" showed very poor outcomes (P < 0.01 for comparison of all). Detailed sequential cytogenetic analysis during follow-up improves prognostication in MDS patients and acknowledges the dynamic biology of the disease. Evidence, time-point, and patterns of cytogenetic clonal evolution should be included into future prognostic scoring systems for MDS.


Assuntos
Deleção Cromossômica , Cromossomos Humanos Par 17/genética , Cromossomos Humanos Par 7/genética , Síndromes Mielodisplásicas/genética , Síndromes Mielodisplásicas/mortalidade , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Intervalo Livre de Doença , Feminino , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Síndromes Mielodisplásicas/terapia , Taxa de Sobrevida
15.
Neurobiol Aging ; 66: 177.e7-177.e10, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29398119

RESUMO

The main genetic risk factors for progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD) are located at chromosome 17q21.31. The identification of risk H1 subhaplotypes suggests that disease-specific variants can be identified by resequencing the 17q21.31 region (1.4 Mb) in carriers of risk H1 subhaplotypes. We hypothesized that PSP/CBD H1 subhaplotype carriers could have undergone a mutational event absent among unaffected carriers leading to the disease risk. We performed this strategy in definite PSP subjects, definite CBD subjects, and healthy controls and tried to replicate the findings in a larger PSP/CBD case-control series. In the resequencing process, 40 candidate variants were identified, but an association between PSP and rs76970862 was replicated only using an unadjusted model. Gene expression association analysis of this variant suggested no potential functional effect. Although our results failed to identify disease-associated variants, it is still possible that the risk of PSP/CBD at chromosome 17 is driven by rare variants, even in PSP/CBD H1 cases or variants located outside the capture regions.


Assuntos
Cromossomos Humanos Par 17/genética , Estudos de Associação Genética , Variação Genética/genética , Tauopatias/genética , Gânglios da Base , Córtex Cerebral , Haplótipos , Heterozigoto , Humanos , Doenças Neurodegenerativas/genética , Receptores de Hormônio Liberador da Corticotropina/genética , Receptores de Hormônio Liberador da Corticotropina/metabolismo , Risco , Paralisia Supranuclear Progressiva/genética , Proteínas tau/genética , Proteínas tau/metabolismo
16.
Taiwan J Obstet Gynecol ; 57(1): 128-132, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29458882

RESUMO

OBJECTIVE: We present prenatal diagnosis and molecular cytogenetic characterization of 17p13.3 microdeletion encompassing YWHAE and CRK but not PAFAH1B1 in a fetus without ultrasound abnormalities. CASE REPORT: A 33-year-old woman underwent amniocentesis at 17 weeks of gestation because of a family history of spinocerebellar atrophy in the husband. Amniocentesis revealed a karyotype of 46,XX. Simultaneously array comparative genomic hybridization (aCGH) analysis (using 60,000 probes) revealed a 0.7-Mb 17p13.3 microdeletion or arr 17p13.3 (1,264,243-1,965,733) × 1 dn [GRCh37 (hg19)] encompassing YWHAE and CRK but not PAFAH1B1. Prenatal ultrasound findings were unremarkable. There were no structural abnormalities of the brain, heart, kidneys, skull, limbs and other internal organs. The parents elected to terminate the pregnancy, and a 268-g fetus was delivered at 19 weeks of gestation with mild facial dysmorphism. Postnatal high-resolution aCGH analysis of the placenta (using 630,000 probes) showed a 0.79-Mb 17p13.3 microdeletion or arr 17p13.3 (1,173,549-1,970,690) × 1 (hg19) encompassing TUSC5, YWHAE, CRK and HIC1 but not PAFAH1B1. Metaphase fluorescence in situ hybridization analysis using the 17p13.3-specific probe of RP11-818O24 revealed a 17p13.3 deletion. CONCLUSION: Fetus with 17p13.3 microdeletion without involving PAFAH1B1 may present no brain abnormalities on fetal ultra sound.


Assuntos
Proteínas 14-3-3/genética , Deleção Cromossômica , Cromossomos Humanos Par 17/genética , Diagnóstico Pré-Natal/métodos , Proteínas Proto-Oncogênicas c-crk/genética , 1-Alquil-2-acetilglicerofosfocolina Esterase/genética , Adulto , Amniocentese , Hibridização Genômica Comparativa/métodos , Feminino , Feto , Humanos , Hibridização in Situ Fluorescente/métodos , Cariótipo , Proteínas Associadas aos Microtúbulos/genética , Gravidez
17.
PLoS One ; 13(1): e0191546, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29352316

RESUMO

BACKGROUND: KANSL1 haploinsufficiency causes Koolen-de Vries syndrome (KdVS), characterized by dysmorphic features and intellectual disability; amiable personality, congenital malformations and seizures also commonly occur. The epilepsy phenotypic spectrum in KdVS is broad, but most individuals have focal seizures with some having a phenotype resembling the self-limited focal epilepsies of childhood (SFEC). We hypothesized that variants in KANSL1 contribute to pathogenesis of SFEC. MATERIALS AND METHODS: We screened KANSL1 for single nucleotide variants in 90 patients with SFEC. We then screened a cohort of 208 patients with two specific SFEC syndromes, childhood epilepsy with centrotemporal spikes (CECTS) and atypical childhood epilepsy with centrotemporal spikes (ACECTS) for KANSL1 variants. The second cohort was also used to evaluate minor allelic variants that appeared overrepresented in the initial cohort. RESULTS: One variant, p.Lys104Thr, was predicted damaging and appeared overrepresented in our 90-patient cohort compared to Genome Aggregation Database (gnomAD) allele frequency (0.217 to 0.116, with no homozygotes in gnomAD). However, there was no difference in p.Lys104Thr allele frequency in the follow-up CECTS/ACECTS cohort and controls. Four rare KANSL1 variants of uncertain significance were identified in the CECTS/ACECTS cohort. DISCUSSION: Our data do not support a major role for KANSL1 variants in pathogenesis of SFEC.


Assuntos
Síndromes Epilépticas/genética , Proteínas Nucleares/genética , Polimorfismo de Nucleotídeo Único , Anormalidades Múltiplas/genética , Substituição de Aminoácidos , Criança , Deleção Cromossômica , Cromossomos Humanos Par 17/genética , Estudos de Coortes , Bases de Dados Genéticas , Epilepsias Parciais/genética , Epilepsia Rolândica/genética , Síndromes Epilépticas/etiologia , Frequência do Gene , Variação Genética , Humanos , Deficiência Intelectual/genética
18.
Nat Commun ; 9(1): 286, 2018 01 18.
Artigo em Inglês | MEDLINE | ID: mdl-29348612

RESUMO

Childhood acute lymphoblastic leukemia (ALL) (age 0-14 years) is 20% more common in Latino Americans than non-Latino whites. We conduct a genome-wide association study in a large sample of 3263 Californian children with ALL (including 1949 of Latino heritage) and 3506 controls matched on month and year of birth, sex, and ethnicity, and an additional 12,471 controls from the Kaiser Resource for Genetic Epidemiology Research on Aging Cohort. Replication of the strongest genetic associations is performed in two independent datasets from the Children's Oncology Group and the California Childhood Leukemia Study. Here we identify new risk loci on 17q12 near IKZF3/ZPBP2/GSDMB/ORMDL3, a locus encompassing a transcription factor important for lymphocyte development (IKZF3), and at an 8q24 region known for structural contacts with the MYC oncogene. These new risk loci may impact gene expression via local (four 17q12 genes) or long-range (8q24) interactions, affecting function of well-characterized hematopoietic and growth-regulation pathways.


Assuntos
Cromossomos Humanos Par 17/genética , Cromossomos Humanos Par 8/genética , Predisposição Genética para Doença/genética , Estudo de Associação Genômica Ampla , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Adolescente , California , Pré-Escolar , Feminino , Frequência do Gene , Predisposição Genética para Doença/etnologia , Hispano-Americanos/genética , Humanos , Lactente , Recém-Nascido , Masculino , Polimorfismo de Nucleotídeo Único , Leucemia-Linfoma Linfoblástico de Células Precursoras/etnologia , Fatores de Risco
19.
Andrologia ; 50(2)2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-28762516

RESUMO

To study the outcome of FISH sperm examination in cases with sperm pathology and outline the potential correlation with certain chromosomal defects. A retrospective study of prospectively collected data was performed in IAKENTRO, Infertility Treatment Center. Rates of abnormal FISH semen examination were compared between male infertility patients and fertile controls. Detection of abnormal FISH semen examination as well as each chromosomal abnormality detected was correlated with each sperm deficiency (asthenozoospermia, oligozoospermia and teratozoospermia) in a univariate regression model. There were 72 male partners included, of which 52 male infertility patients and 20 controls. The rate of abnormal sperm FISH examination was significantly higher in patients' group (55.8% vs. 15.0% for controls, p = .002). Asthenozoospermia, oligozoospermia and teratozoospermia were significantly correlated with detection of abnormal FISH examination (p = .004, p = .01 and p < .001 respectively). Teratospermia was significantly correlated with increased aneuploidy rate for chromosome 17 (p = .005), chromosome X (p = .05) and Y (p = .03). FISH examination reveals pathology in a significant proportion of patients with sperm defects and should be recommended to achieve early detection of chromosomal defects that may postpone favourable reproductive outcome.


Assuntos
Astenozoospermia/fisiopatologia , Oligospermia/fisiopatologia , Análise do Sêmen/métodos , Espermatozoides/patologia , Teratozoospermia/fisiopatologia , Adulto , Aneuploidia , Astenozoospermia/genética , Estudos de Casos e Controles , Cromossomos Humanos Par 17/genética , Cromossomos Humanos X/genética , Cromossomos Humanos Y/genética , Humanos , Hibridização in Situ Fluorescente , Masculino , Oligospermia/genética , Estudos Prospectivos , Estudos Retrospectivos , Teratozoospermia/genética
20.
Genes Chromosomes Cancer ; 57(1): 28-34, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-28913947

RESUMO

Gastric and esophageal cancers frequently show genomic instability and aneuploidy. Chromosomal copy number instability (CIN) is a form of genomic instability that exerts pleiotropic effects on cellular biology and is a source of genetic heterogeneity in a population of cells. CIN results in cell-to-cell variation in chromosome copy number which can be detected and quantified by fluorescence in situ hybridization (FISH). CIN is a biomarker associated with differential response to a number of chemotherapy compounds. We quantified chromosome 17 copy number instability (CIN-17) in 348 gastroesophageal adenocarcinomas by centromeric FISH in cases that were tested for HER2 amplification. We evaluated the association between CIN-17 and clinical outcome after surgical and nonsurgical treatment. CIN-17 was detected in 45.4% (158/348) and extreme CIN-17 in 28.4% (99/348). Extreme CIN-17 had no association with outcome in surgically treated patients. However, in patients treated with conventional radiation and/or chemotherapy, extreme CIN-17 was associated with 55% reduction in overall mortality (hazard ratio, 0.448; 95% confidence interval, 0.263-0.763) after adjusting for age and clinical stage at diagnosis. Extreme CIN-17 is detected in over a quarter of gastroesophageal adenocarcinomas and is a favorable prognostic marker in patients treated nonoperatively.


Assuntos
Adenocarcinoma/genética , Biomarcadores Tumorais/genética , Instabilidade Cromossômica , Cromossomos Humanos Par 17/genética , Neoplasias Esofágicas/genética , Neoplasias Gástricas/genética , Adenocarcinoma/patologia , Idoso , Variações do Número de Cópias de DNA , Neoplasias Esofágicas/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Receptor ErbB-2/genética , Neoplasias Gástricas/patologia
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA