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1.
JMIR Hum Factors ; 11: e51522, 2024 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-38564261

RESUMO

BACKGROUND: More than 18 million cancer survivors are living in the United States. The effects of cancer and its treatments can have cognitive, psychological, physical, and social consequences that many survivors find incredibly disabling. Posttreatment support is often unavailable or underused, especially for survivors living with disabilities. This leaves them to deal with new obstacles and struggles on their own, oftentimes feeling lost during this transition. Mobile health (mHealth) interventions have been shown to effectively aid cancer survivors in dealing with many of the aftereffects of cancer and its treatments; these interventions hold immense potential for survivors living with disabilities. We developed a prototype for WeCanManage, an mHealth-delivered self-management intervention to empower cancer survivors living with disabilities through problem-solving, mindfulness, and self-advocacy training. OBJECTIVE: Our study conducted a heuristic evaluation of the WeCanManage high-fidelity prototype and assessed its usability among cancer survivors with known disabilities. METHODS: We evaluated the prototype using Nielsen's 10 principles of heuristic evaluation with 22 human-computer interaction university students. On the basis of the heuristic evaluation findings, we modified the prototype and conducted usability testing on 10 cancer survivors with a variety of known disabilities, examining effectiveness, efficiency, usability, and satisfaction, including a completion of the modified System Usability Scale (SUS). RESULTS: The findings from the heuristic evaluation were mostly favorable, highlighting the need for a help guide, addressing accessibility concerns, and enhancing the navigation experience. After usability testing, the average SUS score was 81, indicating a good-excellent design. The participants in the usability testing sample expressed positive reactions toward the app's design, educational content and videos, and the available means of connecting with others. They identified areas for improvement, such as improving accessibility, simplifying navigation within the community forums, and providing a more convenient method to access the help guide. CONCLUSIONS: Overall, usability testing showed positive results for the design of WeCanManage. The course content and features helped participants feel heard, understood, and less alone.


Assuntos
Sobreviventes de Câncer , Aplicativos Móveis , Neoplasias , Humanos , Design Centrado no Usuário , Heurística , Interface Usuário-Computador , Poder Psicológico , Neoplasias/terapia
2.
Am J Med Genet A ; 191(2): 357-369, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36349505

RESUMO

Fragile X syndrome (FXS) is caused by hypermethylation of the FMR1 promoter due to the full mutation expansion (full mutation [FM]: CGG ≥ 200 repeats) and silencing of FMR1. Assessment of mosaicism for active-unmethylated alleles has prognostic utility. This study examined relationships between FMR1 methylation in different tissues with FMR1 messenger ribonucleic acid (mRNA) and intellectual functioning in 87 males with FXS (1.89-43.17 years of age). Methylation sensitive Southern blot (mSB) and Methylation Specific-Quantitative Melt Aanalysis (MS-QMA) were used to examine FMR1 methylation. FMR1 mRNA levels in blood showed strong relationships with FMR1 methylation assessed using MS-QMA in blood (n = 68; R2  = 0.597; p = 1.4 × 10-10 ) and buccal epithelial cells (BEC) (n = 62; R2  = 0.24; p = 0.003), with these measures also showing relationships with intellectual functioning scores (p < 0.01). However, these relationships were not as strong for mSB, with ~40% of males with only FM alleles that were 100% methylated and non-mosaic by mSB, showing methylation mosaicism by MS-QMA. This was confirmed through presence of detectable levels of FMR1 mRNA in blood. In summary, FMR1 methylation levels in blood and BEC examined by MS-QMA were significantly associated with FMR1 mRNA levels and intellectual functioning in males with FXS. These relationships were not as strong for mSB, which underestimated prevalence of mosaicism.


Assuntos
Síndrome do Cromossomo X Frágil , Masculino , Humanos , Síndrome do Cromossomo X Frágil/diagnóstico , Síndrome do Cromossomo X Frágil/genética , Mosaicismo , Proteína do X Frágil de Retardo Mental/genética , Metilação de DNA/genética , Mutação , RNA Mensageiro/genética , RNA Mensageiro/metabolismo
3.
Int J Mol Sci ; 23(17)2022 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-36077255

RESUMO

Rosacea is a chronic inflammatory skin disease whose prevalence rates remain unknown in Chile. Laboratory benchmark testing for this disease is not useful, therefore, we aimed to evaluate the gingival crevicular fluid (GCF) levels of extracellular metalloproteinases (MMP)-2 and MMP-9 as novel rosacea biomarkers. We designed a cross-sectional study with a control group. Participants were systemically healthy adults (n = 20) and persons with rosacea (n = 18). We performed a periodontal evaluation and collected gingival crevicular fluid to measure MMP-2 and MMP-9 levels. Analysis showed mean and standard deviation of MMP-9 concentrations in the GCF for patients with rosacea was 764.52 ± 569.83 pg/mL; for healthy patients, it was 260.69 ± 170.43 pg/mL (p < 0.05). The diagnosis of rosacea was responsible for the levels of MMP-9 in the GCF (p < 0.05), as opposed to periodontitis, smoking, and age (p > 0.05). The Area under ROC for MMP-9 was 0.869 (95%, C.I: 0.719−0.956), with a sensitivity of 72.22% and specificity of 81.58% for the diagnosis of rosacea. We conclude that the quantification of MMP-9 in the GCF could be used as a biomarker of rosacea. Also, rosacea was responsible for increasing the levels of MMP-9 in the GCF independent of periodontal status.


Assuntos
Líquido do Sulco Gengival , Rosácea , Adulto , Biomarcadores/análise , Chile , Estudos Transversais , Humanos , Metaloproteinase 9 da Matriz , Rosácea/diagnóstico
4.
JMIR Form Res ; 6(7): e37706, 2022 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-35881439

RESUMO

BACKGROUND: The transition from active treatment to long-term cancer survivorship leaves the needs of many cancer survivors unaddressed as they struggle with physical, cognitive, psychological, and social consequences of cancer and its treatment. The lack of guidance after treatment has forced cancer survivors to manage long-term effects on their own, which has an impact on their overall health, quality of life, and social participation. Mobile health (mHealth) interventions can be used to promote self-management and evidence-informed education. OBJECTIVE: This study aims to design an mHealth app for cancer survivors with disabilities that will offer interventions to improve their quality of life and increase their self-efficacy to manage cancer as a chronic condition. METHODS: We organized 3 co-design workshops with cancer survivors (n=5). These workshops included persona development based on data from 25 interviews with cancer survivors with disabilities; prototype ideation, where we sketched ideas for the prototype; and prototype development, where participants critiqued, and suggested improvements for, the wireframes. RESULTS: These workshops helped us to define the challenges that cancer survivors with disabilities face as well as important considerations when designing an mHealth app for cancer survivors with disabilities, such as the need for including flexibility, engagement, socialization, and a minimalistic design. We also outline guidelines for other researchers to follow when planning their own co-design workshops, which include allowing more time for discussion among participants, having small participant groups, keeping workshops engaging and inclusive, and letting participants dream big. CONCLUSIONS: Using a co-design process aided us in developing a prototype of an mHealth app for cancer survivors with disabilities as well as a list of guidelines that other researchers can use to develop their own co-design workshops and design their app. Furthermore, working together with cancer survivors ensured that the design team had a deeper sense of empathy toward the target users and kept the focus on our ultimate goal: creating something that cancer survivors would want to use and benefit from. Future work will include usability testing of a high-fidelity prototype based on the results of these workshops.

5.
Sci Rep ; 10(1): 11701, 2020 07 16.
Artigo em Inglês | MEDLINE | ID: mdl-32678152

RESUMO

Fragile X syndrome (FXS) is caused by a hypermethylated full mutation (FM) expansion with ≥ 200 CGG repeats, and a decrease in FMR1 mRNA and its protein. However, incomplete silencing from FM alleles has been associated with more severe autism features in FXS males. This study compared scores on the Aberrant Behavior Checklist-Community-FXS version (ABC-CFX) in 62 males affected with FXS (3 to 32 years) stratified based on presence or absence of mosaicism and/or FMR1 mRNA silencing. Associations between ABC-CFX subscales and FMR1 mRNA levels, assessed using real-time PCR relative standard curve method, were also examined. The FXS group mosaic for premutation (PM: 55-199 CGGs) and FM alleles had lower irritability (p = 0.014) and inappropriate speech (p < 0.001) scores compared to males with only FM alleles and complete loss of FMR1 mRNA. The PM/FM mosaic group also showed lower inappropriate speech scores compared to the incomplete silencing (p = 0.002) group. Increased FMR1 mRNA levels were associated with greater irritability (p < 0.001), and lower health-related quality of life scores (p = 0.004), but only in the incomplete silencing FM-only group. The findings suggest that stratification based on CGG sizing and FMR1 mRNA levels may be warranted in future research and clinical trials utilising ABC-CFX subscales as outcome measures.


Assuntos
Alelos , Proteína do X Frágil de Retardo Mental/genética , Síndrome do Cromossomo X Frágil/genética , Mosaicismo , RNA Mensageiro/genética , Projetos de Pesquisa , Adolescente , Adulto , Austrália/epidemiologia , Criança , Pré-Escolar , Chile/epidemiologia , Estudos de Coortes , Metilação de DNA , Síndrome do Cromossomo X Frágil/epidemiologia , Inativação Gênica , Humanos , Masculino , Qualidade de Vida , Reação em Cadeia da Polimerase em Tempo Real , Expansão das Repetições de Trinucleotídeos/genética , Adulto Jovem
6.
J Neurodev Disord ; 11(1): 41, 2019 12 26.
Artigo em Inglês | MEDLINE | ID: mdl-31878865

RESUMO

BACKGROUND: Fragile X syndrome (FXS) is a common cause of intellectual disability and autism spectrum disorder (ASD) usually associated with a CGG expansion, termed full mutation (FM: CGG ≥ 200), increased DNA methylation of the FMR1 promoter and silencing of the gene. Mosaicism for presence of cells with either methylated FM or smaller unmethylated pre-mutation (PM: CGG 55-199) alleles in the same individual have been associated with better cognitive functioning. This study compares age- and sex-matched FM-only and PM/FM mosaic individuals on intellectual functioning, ASD features and maladaptive behaviours. METHODS: This study comprised a large international cohort of 126 male and female participants with FXS (aged 1.15 to 43.17 years) separated into FM-only and PM/FM mosaic groups (90 males, 77.8% FM-only; 36 females, 77.8% FM-only). Intellectual functioning was assessed with age appropriate developmental or intelligence tests. The Autism Diagnostic Observation Schedule-2nd Edition was used to examine ASD features while the Aberrant Behavior Checklist-Community assessed maladaptive behaviours. RESULTS: Comparing males and females (FM-only + PM/FM mosaic), males had poorer intellectual functioning on all domains (p < 0.0001). Although females had less ASD features and less parent-reported maladaptive behaviours, these differences were no longer significant after controlling for intellectual functioning. Participants with PM/FM mosaicism, regardless of sex, presented with better intellectual functioning and less maladaptive behaviours compared with their age- and sex-matched FM-only counterparts (p < 0.05). ASD features were similar between FM-only and PM/FM mosaics within each sex, after controlling for overall intellectual functioning. CONCLUSIONS: Males with FXS had significantly lower intellectual functioning than females with FXS. However, there were no significant differences in ASD features and maladaptive behaviours, after controlling for intellectual functioning, independent of the presence or absence of mosaicism. This suggests that interventions that primarily target cognitive abilities may in turn reduce the severity of maladaptive behaviours including ASD features in FXS.


Assuntos
Transtorno do Espectro Autista , Sintomas Comportamentais , Síndrome do Cromossomo X Frágil , Deficiência Intelectual , Mosaicismo , Adolescente , Adulto , Transtorno do Espectro Autista/etiologia , Transtorno do Espectro Autista/genética , Transtorno do Espectro Autista/fisiopatologia , Sintomas Comportamentais/etiologia , Sintomas Comportamentais/genética , Sintomas Comportamentais/fisiopatologia , Criança , Pré-Escolar , Estudos de Coortes , Feminino , Proteína do X Frágil de Retardo Mental/genética , Síndrome do Cromossomo X Frágil/complicações , Síndrome do Cromossomo X Frágil/genética , Síndrome do Cromossomo X Frágil/fisiopatologia , Humanos , Lactente , Deficiência Intelectual/etiologia , Deficiência Intelectual/genética , Deficiência Intelectual/fisiopatologia , Masculino , Mutação , Fenótipo , Fatores Sexuais , Adulto Jovem
7.
Mol Autism ; 10: 21, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31073396

RESUMO

Background: Fragile X syndrome (FXS) is a common monogenic cause of intellectual disability with autism features. While it is caused by loss of the FMR1 product (FMRP), mosaicism for active and inactive FMR1 alleles, including alleles termed premutation (PM: 55-199 CGGs), is not uncommon. Importantly, both PM and active full mutation (FM: ≥ 200 CGGs) alleles often express elevated levels of mRNA that are thought to be toxic. This study determined if complete FMR1 mRNA silencing from FM alleles and/or levels of FMR1 mRNA (if present) in blood are associated with intellectual functioning and autism features in FXS. Methods: The study cohort included 98 participants (70.4% male) with FXS (FM-only and PM/FM mosaic) aged 1-43 years. A control group of 14 females were used to establish control FMR1 mRNA reference range. Intellectual functioning and autism features were assessed using the Mullen Scales of Early Learning or an age-appropriate Wechsler Scale and the Autism Diagnostic Observation Schedule-2nd Edition (ADOS-2), respectively. FMR1 mRNA was analysed in venous blood collected at the time of assessments, using the real-time PCR relative standard curve method. Results: Females with FXS had significantly higher levels of FMR1 mRNA (p < 0.001) than males. FMR1 mRNA levels were positively associated with age (p < 0.001), but not with intellectual functioning and autistic features in females. FM-only males (aged < 19 years) expressing FM FMR1 mRNA had significantly higher ADOS calibrated severity scores compared to FM-only males with completely silenced FMR1 (p = 0.011). However, there were no significant differences between these subgroups on intellectual functioning. In contrast, decreased levels of FMR1 mRNA were associated with decreased intellectual functioning in FXS males (p = 0.029), but not autism features, when combined with the PM/FM mosaic group. Conclusion: Incomplete silencing of toxic FM RNA may be associated with autistic features, but not intellectual functioning in FXS males. While decreased levels of mRNA may be more predictive of intellectual functioning than autism features. If confirmed in future studies, these findings may have implications for patient stratification, outcome measure development, and design of clinical and pre-clinical trials in FXS.


Assuntos
Alelos , Transtorno Autístico/complicações , Transtorno Autístico/genética , Síndrome do Cromossomo X Frágil/complicações , Síndrome do Cromossomo X Frágil/genética , Inativação Gênica , Mutação/genética , Adolescente , Adulto , Fatores Etários , Criança , Pré-Escolar , Feminino , Proteína do X Frágil de Retardo Mental/sangue , Proteína do X Frágil de Retardo Mental/genética , Proteína do X Frágil de Retardo Mental/metabolismo , Humanos , Lactente , Deficiência Intelectual/genética , Masculino , Pessoa de Meia-Idade , Fenótipo , RNA Mensageiro/sangue , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Adulto Jovem
8.
Rev Med Chil ; 147(1): 61-64, 2019.
Artigo em Espanhol | MEDLINE | ID: mdl-30848766

RESUMO

BACKGROUND: Cytogenetic abnormalities observed in the bone marrow of patients with multiple myeloma (MM) are an important prognostic factor for risk stratification. AIM: To investigate karyotype characteristics and frequency of the high-risk cytogenetic abnormalities t(4;14), t(14;16) and del(17p) in Chilean patients with MM. MATERIAL AND METHODS: We studied 30 patients with MM by conventional cytogenetics (CC) and fluorescent in situ hybridization of plasma cells selected using cytoplasmic immunoglobulin staining (cIg-FISH). RESULTS: Overall, the two techniques in combination allowed us to identify clonal genetic abnormalities in 47% of patients. The t(4;14) abnormality was observed in 19% of patients, del(17p) was observed in 10% of patients, and t(14;16) was not detected. CONCLUSIONS: Our results showed frequencies of high-risk abnormalities similar to those reported abroad. Cytogenetic studies should be performed routinely for all MM patients at the moment of diagnosis.


Assuntos
Aberrações Cromossômicas , Mieloma Múltiplo/genética , Adulto , Idoso , Chile , Análise Citogenética/métodos , Feminino , Humanos , Hibridização in Situ Fluorescente/métodos , Cariótipo , Masculino , Pessoa de Meia-Idade , Valores de Referência , Medição de Risco/métodos , Fatores de Risco
9.
Chemosphere ; 226: 24-35, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30913425

RESUMO

Methane is one of the most important greenhouse gases emitted from natural and human activities. It is scarcely soluble in water; thus, it has a low bioavailability for microorganisms able to degrade it. In this work, the capacity of the fungus Fusarium solani to improve the solubility of methane in water and to biodegrade methane was assayed. Experiments were performed in microcosms with vermiculite as solid support and mineral media, at temperatures between 20 and 35 °C and water activities between 0.9 and 0.95, using pure cultures of F. solani and a methanotrophic consortium (Methylomicrobium album and Methylocystis sp) as a control. Methane was the only carbon and energy source. Results indicate that using thermally inactivated biomass of F. solani, decreases the partition coefficient of methane in water up to two orders of magnitude. Moreover, F. solani can degrade methane, in fact at 35 °C and the highest water activity, the methane degradation rate attained by F. solani was 300 mg m-3 h-1, identical to the biodegradation rate achieved by the consortium of methanotrophic bacteria.


Assuntos
Biodegradação Ambiental/efeitos dos fármacos , Fusarium/química , Metano/química , Fusarium/patogenicidade
10.
Rev. méd. Chile ; 147(1): 61-64, 2019. tab, graf
Artigo em Espanhol | LILACS | ID: biblio-1043152

RESUMO

Background: Cytogenetic abnormalities observed in the bone marrow of patients with multiple myeloma (MM) are an important prognostic factor for risk stratification. Aim: To investigate karyotype characteristics and frequency of the high-risk cytogenetic abnormalities t(4;14), t(14;16) and del(17p) in Chilean patients with MM. Material and Methods: We studied 30 patients with MM by conventional cytogenetics (CC) and fluorescent in situ hybridization of plasma cells selected using cytoplasmic immunoglobulin staining (cIg-FISH). Results: Overall, the two techniques in combination allowed us to identify clonal genetic abnormalities in 47% of patients. The t(4;14) abnormality was observed in 19% of patients, del(17p) was observed in 10% of patients, and t(14;16) was not detected. Conclusions: Our results showed frequencies of high-risk abnormalities similar to those reported abroad. Cytogenetic studies should be performed routinely for all MM patients at the moment of diagnosis.


Assuntos
Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Idoso , Aberrações Cromossômicas , Mieloma Múltiplo/genética , Valores de Referência , Chile , Fatores de Risco , Hibridização in Situ Fluorescente/métodos , Medição de Risco/métodos , Análise Citogenética/métodos , Cariótipo
11.
Rev Med Chil ; 145(7): 854-861, 2017 Jul.
Artigo em Espanhol | MEDLINE | ID: mdl-29182193

RESUMO

BACKGROUND: In 20% of neurodevelopmental disorders (NDD) and congenital abnormalities (CA) the cause would be a genomic imbalance detectable only by chromosomal microarrays (CMA). AIM: To analyze the results of CMA performed at the INTA Laboratory of Molecular Cytogenetics, during a period of four years in patients with NDD or CA. MATERIAL AND METHODS: Retrospective study that included all CMA reports of Chilean patients. Age, sex, clinical diagnosis and origin were analyzed, as well as the characteristics of the finding. The percentage of cases diagnosed by CMA was calculated considering all patients with pathogenic (PV) or probably pathogenic variants (VLP). Finally, we studied the association between patients' characteristics and a positive CMA outcome. RESULTS: A total of 236 reports were analyzed. The median age was 5.41 (range 2.25-9.33) years, and 59% were men. Ninety chromosomal imbalances were found, which corresponded mainly to deletions (53.3%), with a median size of 1.662 (range 0.553-6.673) Megabases. The diagnostic rate of CMA in Chilean patients from all over the country was 19.2%. There was a close relationship between the patient's sex and the detection of VLP/VP (p = 0.034). CONCLUSIONS: Our diagnostic rate and the association between female sex and a higher percentage of diagnosed cases are concordant with other international studies. Therefore, CMA is a valid diagnostic tool in the Chilean population.


Assuntos
Anormalidades Congênitas/diagnóstico , Anormalidades Congênitas/genética , Análise em Microsséries/métodos , Transtornos do Neurodesenvolvimento/diagnóstico , Transtornos do Neurodesenvolvimento/genética , Criança , Pré-Escolar , Chile , Feminino , Humanos , Masculino , Estudos Retrospectivos
12.
Appl Microbiol Biotechnol ; 101(17): 6765-6777, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28685193

RESUMO

Polycyclic aromatic hydrocarbons (PAHs) and volatile organic compounds (VOCs) are important indoor contaminants. Their hydrophobic nature hinders the possibility of biological abatement using biofiltration. Our aim was to establish whether the use of a consortium of Fusarium solani and Rhodococcus erythropolis shows an improved performance (in terms of mineralization rate and extent) towards the degradation of formaldehyde, as a slightly polar VOC; toluene, as hydrophobic VOC; and benzo[α]pyrene (BaP) as PAH at low concentrations compared to a single-species biofilm in serum bottles with vermiculite as solid support to mimic a biofilter and to relate the possible improvements with the surface hydrophobicity and partition coefficient of the biomass at three different temperatures. Results showed that the hydrophobicity of the surface of the biofilms was affected by the hydrophobicity of the carbon source in F. solani but it did not change in R. erythropolis. Similarly, the partition coefficients of toluene and BaP in F. solani biomass (both as pure culture and consortium) show a reduction of up to 38 times compared to its value in water, whereas this reduction was only 1.5 times in presence of R. erythropolis. Despite that increments in the accumulated CO2 and its production rate were found when F. solani or the consortium was used, the mineralization extent of toluene was below 25%. Regarding BaP degradation, the higher CO2 production rates and percent yields were obtained when a consortium of F. solani and R. erythropolis was used, despite a pure culture of R. erythropolis exhibits poor mineralization of BaP.


Assuntos
Benzo(a)pireno/metabolismo , Biodegradação Ambiental , Formaldeído/metabolismo , Fusarium/metabolismo , Rhodococcus/metabolismo , Tolueno/metabolismo , Poluição do Ar em Ambientes Fechados/prevenção & controle , Biomassa , Filtração/instrumentação , Consórcios Microbianos/fisiologia , Hidrocarbonetos Policíclicos Aromáticos/metabolismo , Compostos Orgânicos Voláteis/metabolismo
13.
Rev. méd. Chile ; 145(7): 854-861, jul. 2017. tab, graf
Artigo em Espanhol | LILACS | ID: biblio-902558

RESUMO

Background: In 20% of neurodevelopmental disorders (NDD) and congenital abnormalities (CA) the cause would be a genomic imbalance detectable only by chromosomal microarrays (CMA). Aim: To analyze the results of CMA performed at the INTA Laboratory of Molecular Cytogenetics, during a period of four years in patients with NDD or CA. Material and Methods: Retrospective study that included all CMA reports of Chilean patients. Age, sex, clinical diagnosis and origin were analyzed, as well as the characteristics of the finding. The percentage of cases diagnosed by CMA was calculated considering all patients with pathogenic (PV) or probably pathogenic variants (VLP). Finally, we studied the association between patients' characteristics and a positive CMA outcome. Results: A total of 236 reports were analyzed. The median age was 5.41 (range 2.25-9.33) years, and 59% were men. Ninety chromosomal imbalances were found, which corresponded mainly to deletions (53.3%), with a median size of 1.662 (range 0.553-6.673) Megabases. The diagnostic rate of CMA in Chilean patients from all over the country was 19.2%. There was a close relationship between the patient's sex and the detection of VLP/VP (p = 0.034). Conclusions: Our diagnostic rate and the association between female sex and a higher percentage of diagnosed cases are concordant with other international studies. Therefore, CMA is a valid diagnostic tool in the Chilean population.


Assuntos
Humanos , Masculino , Feminino , Pré-Escolar , Criança , Anormalidades Congênitas/diagnóstico , Anormalidades Congênitas/genética , Análise em Microsséries/métodos , Transtornos do Neurodesenvolvimento/diagnóstico , Transtornos do Neurodesenvolvimento/genética , Chile , Estudos Retrospectivos
14.
Mol Syndromol ; 7(5): 287-291, 2016 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-27867344

RESUMO

Chromosome 7q11.23 duplication syndrome is a well-recognised syndrome which involves the duplication of the same genes located in the Williams-Beuren critical region. However, in 2010, 4 patients were reported with a microduplication only in the HIP1 and YWHAG genes. We refer to this as a distal 7q11.23 duplication (dup7q11.23D). Here, we report the fifth de novo patient with dup7q11.23D, whose symptoms may be explained by YWHAG overexpression as was demonstrated recently in mice and obese patients. Finally, further studies will be necessary to delineate this emerging microduplication syndrome.

15.
Genet Res (Camb) ; 98: e11, 2016 06 28.
Artigo em Inglês | MEDLINE | ID: mdl-27350105

RESUMO

Fragile X syndrome (FXS) is the most common form of inherited intellectual disability (ID) and co-morbid autism. It is caused by an amplification of the CGG repeat (>200), which is known as the full mutation, within the 5'UTR of the FMR1 gene. Expansions between 55-200 CGG repeats are termed premutation and are associated with a greater risk for fragile X-associated tremor/ataxia syndrome and fragile X-associated premature ovarian insufficiency. Intermediate alleles, also called the grey zone, include approximately 45-54 repeats and are considered borderline. Individuals with less than 45 repeats have a normal FMR1 gene. We report the occurrence of CGG expansions of the FMR1 gene in Chile among patients with ID and families with a known history of FXS. Here, we present a retrospective review conducted on 2321 cases (2202 probands and 119 relatives) referred for FXS diagnosis and cascade screening at the Institute of Nutrition and Food Technology (INTA), University of Chile. Samples were analysed using traditional cytogenetic methods and/or PCR. Southern blot was used to confirm the diagnosis. Overall frequency of FMR1 expansions observed among probands was 194 (8·8%), the average age of diagnosis was 8·8 ± 5·4 years. Of 119 family members studied, 72 (60%) were diagnosed with a CGG expansion. Our results indicated that the prevalence of CGG expansions of the FMR1 gene among probands is relatively higher than other populations. The average age of diagnosis is also higher than reference values. PCR and Southern blot represent a reliable molecular technique in the diagnosis of FXS.


Assuntos
Proteína do X Frágil de Retardo Mental/genética , Síndrome do Cromossomo X Frágil/genética , Predisposição Genética para Doença , Mutação/genética , Sequências Repetitivas de Ácido Nucleico/genética , Adolescente , Adulto , Southern Blotting , Criança , Pré-Escolar , Família , Feminino , Testes Genéticos , Genótipo , Humanos , Lactente , Masculino , Reação em Cadeia da Polimerase , Estudos Retrospectivos , Adulto Jovem
16.
J Appl Genet ; 57(1): 63-9, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26069167

RESUMO

Intellectual disability (ID) and global development delay (GDD) are caused by genetic factors such as subtelomeric rearrangements (SR) in 25 % of patients. There are several assays currently available to detect SR, but subtelomeric fluorescence in situ hybridisation (Subt-FISH) and subtelomeric multiplex ligation-dependent probe amplification (Subt-MLPA) have been the most frequently used. However, the diagnostic yield of each technique has not been compared. We reviewed the results of SR screening over a ten-year period in Chilean patients with ID/GDD using Subt-FISH and/or Subt-MLPA, compared the diagnostic yield of both tools and reviewed the corresponding literature. A total of 383 cases were included in this study, of which 53.8 % were males. The overall diagnostic yield was 8.9 % between both methods, but Subt-MLPA showed a higher performance than Subt-FISH (p = 0.002). A total of 4,181 patients with ID/GDD have been studied worldwide with Subt-MLPA and other subtelomeric assays, and 244 (5.84 %) had a pathogenic SR. It is estimated that Subt-MLPA may detect 92.6 % of the total cases with SR. The capacity of detecting tandem duplication and other critical regions, as well as the use of two MLPA kits, may explain the higher performance of this tool over Subt-FISH. Therefore, we recommend the use of this subtelomeric method as a cost-effective way to study ID/GDD patients.


Assuntos
Aberrações Cromossômicas , Rearranjo Gênico , Testes Genéticos/métodos , Adolescente , Criança , Pré-Escolar , Chile , Análise Citogenética , Deficiências do Desenvolvimento/genética , Feminino , Humanos , Hibridização in Situ Fluorescente , Deficiência Intelectual/genética , Masculino , Reação em Cadeia da Polimerase Multiplex
17.
Clin Chem ; 62(2): 343-52, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26715660

RESUMO

BACKGROUND: FMR1 full mutations (FMs) (CGG expansion >200) in males mosaic for a normal (<45 CGG) or gray-zone (GZ) (45-54 CGG) allele can be missed with the standard 2-step fragile X syndrome (FXS) testing protocols, largely because the first-line PCR tests showing a normal or GZ allele are not reflexed to the second-line test that can detect FM. METHODS: We used methylation-specific quantitative melt analysis (MS-QMA) to determine the prevalence of cryptic FM alleles in 2 independent cohorts of male patients (994 from Chile and 2392 from Australia) referred for FXS testing from 2006 to 2013. All MS-QMA-positive cases were retested with commercial triplet primed PCR, methylation-sensitive Southern blot, and a methylation-specific EpiTYPER-based test. RESULTS: All 38 FMs detected with the standard 2-step protocol were detected with MS-QMA. However, MS-QMA identified methylation mosaicism in an additional 15% and 11% of patients in the Chilean and Australian cohorts, respectively, suggesting the presence of a cryptic FM. Of these additional patients, 57% were confirmed to carry cryptic expanded alleles in blood, buccal mucosa, or saliva samples. Further confirmation was provided by identifying premutation (CGG 55-199) alleles in mothers of probands with methylation-sensitive Southern blot. Neurocognitive assessments showed that low-level mosaicism for cryptic FM alleles was associated with cognitive impairment or autism. CONCLUSIONS: A substantial number of mosaic FM males who have cognitive impairment or autism are not diagnosed with the currently recommended 2-step testing protocol and can be identified with MS-QMA as a first-line test.


Assuntos
Alelos , Síndrome do Cromossomo X Frágil/genética , Técnicas Genéticas , Adolescente , Adulto , Southern Blotting , Criança , Pré-Escolar , Estudos de Coortes , Ilhas de CpG , Metilação de DNA , Proteína do X Frágil de Retardo Mental/genética , Proteína do X Frágil de Retardo Mental/metabolismo , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Mosaicismo , Reação em Cadeia da Polimerase/métodos , Adulto Jovem
18.
Electron. j. biotechnol ; 15(3): 7-7, May 2012. ilus, tab
Artigo em Inglês | LILACS | ID: lil-640551

RESUMO

Background: The behaviour of two biotrickling filters connected in serie (BTF) inoculated with Acidithiobacillus thiooxidans and Thiobacillus thioparus, biodegrading hydrogen sulphide (H2S) and dimethyl sulphide (DMS) simultaneously were studied. A model which considers gas to liquid mass transfer and biooxidation in the biofilm attached to the support is developed. Additionally, a fixed bed biotrickling filter where the microorganism is immobilized in a biofilm which degrades a mixture of H2S and DMS is implemented. Validation of the model was carried out using experimental data obtained at different H2S and DMS loads. Results: The inhibitory effect caused by the presence of H2S on the DMS is observed, which is evidenced by the decrease of the DMS removal efficiency from 80 to 27 percent, due to the preference that T. thioparus has by simple metabolism. H2S is not affected by the DMS, with removal efficiencies of 95 to 97 percent, but it decreases at high concentrations of the compound, due to the inhibition of metabolism by high H2S input loads. The model which describes the BFT fits successfully with the experimental results and it has a high sensitivity to inhibition parameters. Conclusion: It is shown that the microorganism has a high affinity for H2S, producing substrate inhibition when the concentration is high. The H2S is able to inhibit the DMS biooxidation, whereas the DMS does not affect the H2S biooxidation.


Assuntos
Filtração , Sulfeto de Hidrogênio , Modelos Teóricos , Sulfetos , Thiobacillus , Acidithiobacillus thiooxidans
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