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1.
Front Genet ; 14: 1304458, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38125748

RESUMO

Primary carnitine deficiency (PCD) caused by pathogenic variants in the solute carrier family 22 member 5 (SLC22A5) gene is a rare autosomal recessive disease that results in defective fatty acid oxidation. PCD can be detected through tandem mass spectrometry (MS/MS), but transplacental transport of free carnitine from mothers may cause false negatives or positives during newborn screening (NBS). This study aimed to analyze the genetic characteristics of SLC22A5 and estimate the prevalence of PCD in the Chinese population, providing useful information for NBS and genetic counseling. We manually curated SLC22A5 pathogenic or likely pathogenic (P/LP) variants according to the American College of Medical Genetics and Genomics (ACMG) guidelines and identified 128 P/LP variants. Based on the China Neonatal Genomes Project (CNGP), the estimated PCD prevalence was 1:17,456, which was higher than that in other populations. The genotype-phenotype association analysis showed that patients carrying homozygous c.760C>T and c.844C>T were more likely to present cardiomyopathy, whereas those carrying homozygous c.1400C>G were more likely to be asymptomatic (all p-values < 0.05). We found that there was no significant difference in initial C0 concentrations between patients and carriers, but there was a significant difference in the second-tier screening of C0 concentration between them (p-value < 0.05). We established a cost-effective variant panel containing 10 high-frequency sites and developed a screening algorithm incorporating gene panels with MS/MS, which could rescue one more patient who was undetected from MS/MS. In conclusion, the prevalence of PCD in the Chinese population is relatively high. The combination of conventional NBS with genetic sequencing is suggested for early diagnosis of PCD.

2.
Pathology ; 55(7): 922-928, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37833206

RESUMO

An investigator-initiated, Australia-wide multi-centre retrospective observational study was undertaken to investigate the real-world prevalence of programmed death ligand-1 (PD-L1) expression in non-small cell lung carcinoma (NSCLC). Multiple centres around Australia performing PD-L1 immunohistochemistry (IHC) were invited to participate. Histologically confirmed NSCLC of any stage with a PD-L1 IHC test performed for persons aged ≥18 years between 1 January 2018 and 1 January 2020, and eligible for review, were identified at each centre, followed by data extraction and de-identification, after which data were submitted to a central site for collation and analysis. In total data from 6690 eligible PD-L1 IHC tests from histologically (75%) or cytologically (24%) confirmed NSCLC of any stage were reviewed from persons with a median age of 70 years, 43% of which were female. The majority (81%) of tests were performed using the PD-L1 IHC SP263 antibody with the Ventana BenchMark Ultra platform and 19% were performed using Dako PD-L1 IHC 22C3 pharmDx assay. Reported PD-L1 tumour proportion score (TPS) was ≥50% for 30% of all tests, with 62% and 38% scoring PD-L1 ≥1% and <1%, respectively. Relative prevalence of clinicopathological features with PD-L1 scores dichotomised to <50% and ≥50%, or to <1% and ≥1%, were examined. Females scored ≥1% slightly more often than males (64% vs 61%, respectively, p=0.013). However, there was no difference between sexes or age groups (<70 or ≥70 years) where PD-L1 scored ≥50%. Specimens from patients with higher stage (III/IV) scored ≥1% or ≥50% marginally more often compared to specimens from patients with lower stage (I/II) (p≤0.002). Proportions of primary and metastatic specimens did not differ where PD-L1 TPS was ≥1%, however more metastatic samples scored TPS ≥50% than primary samples (metastatic vs primary; 34% vs 27%, p<0.001). Cytology and biopsy specimens were equally reported, at 63% of specimens, to score TPS ≥1%, whereas cytology samples scored TPS ≥50% slightly more often than biopsy samples (34% vs 30%, respectively, p=0.004). Resection specimens (16% of samples tested) were reported to score TPS ≥50% or ≥1% less often than either biopsy or cytology samples (p<0.001). There was no difference in the proportion of tests with TPS ≥1% between PD-L1 IHC assays used, however the proportion of tests scored at TPS ≥50% was marginally higher for 22C3 compared to SP263 (34% vs 29%, respectively, p<0.001). These real-world Australian data are comparable to some previously published global real-world data, with some differences noted.


Assuntos
Antígeno B7-H1 , Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Adolescente , Adulto , Idoso , Feminino , Humanos , Masculino , Austrália/epidemiologia , Antígeno B7-H1/metabolismo , Biomarcadores Tumorais/análise , Carcinoma Pulmonar de Células não Pequenas/epidemiologia , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Neoplasias Pulmonares/epidemiologia , Neoplasias Pulmonares/metabolismo , Prevalência
3.
Int Rev Psychiatry ; 34(7-8): 676-688, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36786112

RESUMO

22q11.2 deletion syndrome (22q.11.2DS) might be one of the strongest genetic risk factors for psychosis, but robust estimates of prevalence and incidence of psychotic disorders in this condition are not available. To address this gap, we performed a multistep systematic PRISMA/MOOSE-compliant literature search of articles reporting prevalence (primary outcome) or incidence (secondary outcome) of psychotic disorders in 22q11.2DS samples (protocol: https://osf.io/w6hpg) using random-effects meta-analysis, subgroup analyses and meta-regressions. The pooled prevalence of psychotic disorders was 11.50% (95%CI:9.40-14.00%), largely schizophrenia (9.70%, 95%CI:6.50-14.20). Prevalence was significantly higher in samples with a mean age over 18 years, with both psychiatric and non-psychiatric comorbidities and recruited from healthcare services (compared to the community). Mean age was also significantly positively associated with prevalence in meta-regressions (p < 0.01). The pooled incidence of psychotic disorders was 10.60% (95%CI:6.60%-16.70%) at a mean follow-up time of 59.27 ± 40.55 months; meta-regressions were not significant. To our knowledge, this is the first comprehensive systematic review and meta-analysis of the prevalence and incidence of psychotic disorders in 22q11.2DS individuals. It demonstrates that around one in ten individuals with 22q11.2DS displays comorbid psychotic disorders, and around one in ten will develop psychosis in the following five years, indicating that preventive approaches should be implemented systematically in 22q11.2DS.


Assuntos
Síndrome de DiGeorge , Transtornos Psicóticos , Esquizofrenia , Humanos , Síndrome de DiGeorge/epidemiologia , Síndrome de DiGeorge/complicações , Síndrome de DiGeorge/genética , Incidência , Prevalência , Transtornos Psicóticos/epidemiologia , Transtornos Psicóticos/etiologia , Esquizofrenia/epidemiologia , Esquizofrenia/genética
4.
Genes (Basel) ; 11(3)2020 03 04.
Artigo em Inglês | MEDLINE | ID: mdl-32143290

RESUMO

MYO6 is known as a genetic cause of autosomal dominant and autosomal recessive inherited hearing loss. In this study, to clarify the frequency and clinical characteristics of hearing loss caused by MYO6 gene mutations, a large-scale genetic analysis of Japanese patients with hearing loss was performed. By means of massively parallel DNA sequencing (MPS) using next-generation sequencing for 8074 Japanese families, we found 27 MYO6 variants in 33 families, 22 of which are novel. In total, 2.40% of autosomal dominant sensorineural hearing loss (ADSNHL) in families in this study (32 out of 1336) was found to be caused by MYO6 mutations. The present study clarified that most cases showed juvenile-onset progressive hearing loss and their hearing deteriorated markedly after 40 years of age. The estimated hearing deterioration was found to be 0.57 dB per year; when restricted to change after 40 years of age, the deterioration speed was accelerated to 1.07 dB per year. To obtain supportive evidence for pathogenicity, variants identified in the patients were introduced to MYO6 cDNA by site-directed mutagenesis and overexpressed in epithelial cells. They were then assessed for their effects on espin1-induced microvilli formation. Cells with wildtype myosin 6 and espin1 co-expressed created long microvilli, while co-expression with mutant constructs resulted in severely shortened microvilli. In conclusion, the present data clearly showed that MYO6 is one of the genes to keep in mind with regard to ADSNHL, and the molecular characteristics of the identified gene variants suggest that a possible pathology seems to result from malformed stereocilia of the cochlear hair cells.


Assuntos
Surdez/genética , Perda Auditiva Neurossensorial/genética , Cadeias Pesadas de Miosina/genética , Adolescente , Adulto , Idoso , Criança , Surdez/patologia , Feminino , Ligação Genética/genética , Genótipo , Células Ciliadas Auditivas/metabolismo , Células Ciliadas Auditivas/patologia , Perda Auditiva Neurossensorial/epidemiologia , Perda Auditiva Neurossensorial/patologia , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Masculino , Pessoa de Meia-Idade , Mutação/genética , Linhagem , Fenótipo , Adulto Jovem
5.
Clin Otolaryngol ; 43(6): 1560-1565, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30152142

RESUMO

OBJECTIVE (S): To estimate the prevalence and associations among rhinosinusitis symptoms, smoking and chronic obstructive pulmonary disease (COPD). DESIGN: Cross-sectional study. SETTING: Population-based. PARTICIPANTS: All adults aged 40 years or more living in the selected households in the city of Florianópolis (Florianópolis, Santa Catarina, Brazil). MAIN OUTCOME MEASURES: Assessment instruments comprised household interviews, anthropometric measurements and spirometry. Rhinosinusitis symptoms were based on the responses to the 22-item Sinonasal Outcome Test (SNOT-22) questionnaire; smoking status was defined by the criteria of the CDC, and the functional diagnosis of COPD was done by spirometry. RESULTS: The prevalence (n = 1056) of rhinosinusitis symptoms, smoking and COPD was 14.7%, 17.9% and 8.7%, respectively. Multivariate analysis showed that, with the exception of COPD, all other clinical variables (smoking, previous diagnosis of rhinitis, previous diagnosis of gastritis/ulcer/gastroesophageal reflux, and symptoms of depression) remained associated with higher prevalence of rhinosinusitis symptoms. CONCLUSIONS: Rhinosinusitis symptoms were common both in smokers and in patients with COPD. However, only tobacco was significantly associated with rhinosinusitis symptoms and can act as a cofounder in the association between COPD and rhinosinusitis symptoms.


Assuntos
Vigilância da População , Doença Pulmonar Obstrutiva Crônica/epidemiologia , Rinite/complicações , Medição de Risco/métodos , Sinusite/complicações , Fumar/efeitos adversos , Adulto , Brasil/epidemiologia , Estudos Transversais , Feminino , Volume Expiratório Forçado , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Doença Pulmonar Obstrutiva Crônica/etiologia , Fatores de Risco , Inquéritos e Questionários
6.
Br J Nutr ; 116(7): 1236-1245, 2016 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-27609220

RESUMO

To examine the prevalence of folate inadequacy and toxicity based on usual intakes from food and supplements, as well as biomarkers of folate, secondary data analyses were performed using cross-sectional, nationally representative data from the Canadian Community Health Survey, Cycle 2.2 (n 32 776), as well as biomarker data from the Canadian Health Measures Survey, Cycles 1, 2 and 3 (n 15 754). On the basis of unfortified food sources, Canadians would struggle to consume adequate amounts of folate. When folate intakes from all food sources were considered, the overall prevalence of folate inadequacy was low across all age/sex groups, with the exception of females >70 years. However, >10 % of supplement users were above the tolerable upper intake level, increasing to almost 18 % when overage factors were accounted for. In addition, between 20 and 52 % of supplement users had elevated erythrocyte folate concentrations, depending on the cut-off used. Results from this study suggest that insufficient dietary intakes of folate in Canadians have been ameliorated because of the fortification policy, although folate inadequacy still exists across all age groups. However, supplement users appear to be at an increased risk of folic acid (FA) overconsumption as well as elevated erythrocyte folate. As such, the general population should be informed of the potential risks of FA overconsumption resulting from supplement use. This study suggests a need for more careful assessment of the risks and benefits of food fortification, particularly fortification above mandated levels, and FA supplement use in the general population.


Assuntos
Dieta , Ácido Fólico/administração & dosagem , Ácido Fólico/toxicidade , Adolescente , Adulto , Idoso , Canadá/epidemiologia , Criança , Pré-Escolar , Estudos Transversais , Suplementos Nutricionais/efeitos adversos , Eritrócitos/química , Feminino , Ácido Fólico/sangue , Deficiência de Ácido Fólico/epidemiologia , Alimentos Fortificados , Inquéritos Epidemiológicos , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Fatores de Risco
7.
Springerplus ; 4: 397, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26261755

RESUMO

PURPOSE: To reveal the prevalence of low back pain (LBP) and association between LBP and patient-reported QOL outcomes (JOABPEQ and SRS-22r) in patients with adolescent idiopathic scoliosis (AIS) without corrective surgery. METHODS: Ninety-eight female patients with AIS without corrective surgery who answered JOABPEQ, SRS-22r, and VAS for LBP were included. The scores of all subdomains in JOABPEQ and SRS-22r were calculated. From the standing radiographs, we measured the Risser grade and radiographic parameters regarding the curve magnitude, coronal and sagittal balance, and spinopelvic alignment. Furthermore, we recorded whether the patients were undergoing brace treatment at the time of visiting our outpatient clinic. The patients with VAS >30 mm (moderate or severe LBP) were designated as Group P; VAS ≤30 mm, Group N. All variables were compared between the groups. RESULTS: The prevalence of LBP (VAS >0 mm) was 34.7% and that of moderate or severe LBP was 16.2%. All subdomain scores in JOABPEQ and those for function and pain in SRS-22r were significantly smaller in Group P than Group N. The subdomain scores for self-image and satisfaction/dissatisfaction with management in SRS-22r did not differ between the groups. The age, Risser grade, radiographic parameters, and whether the patients were undergoing brace treatment did not differ between the groups. CONCLUSIONS: The prevalence of LBP was 34.7%, which was approximately three times higher than that previously reported in Japanese pupils without scoliosis. The patients with LBP demonstrated poorer QOL outcomes associated with LBP regardless of radiographic parameters, patients' self-image and satisfaction with treatment.

8.
Am J Med Genet A ; 167(7): 1560-4, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-25944702

RESUMO

We reviewed the health records of pediatric patients with 22q11.2 deletion syndrome (22q11.2 DS) seen over a 5-year period in our 22q11.2 DS multidisciplinary clinic. We determined the prevalence of thyroid dysfunction in this population, in comparison to general population data. Statistical tests were applied to investigate trends in gender differences, thyroid disease subtype and co-morbid conditions in the patients identified with thyroid disease. Of 169 subjects (92 male, 77 female) 9.5% had overt thyroid disease; of these, 1.8% had hyperthyroidism and 7.7% had hypothyroidism; 42% of patients with subclinical or prodromal thyroid disease progressed to overt disease. Our data indicate that thyroid disease prevalence in the 22q11DS pediatric population is significantly higher than that in the general pediatric population Furthermore, over 1/3 of patients in our study population who presented with subclinical thyroid disease progressed to overt disease, requiring medical therapy. Thyroid disease screening should be incorporated into routine medical management of children with 22q11.2 DS. Guidelines for screening individuals with 22q11.2 DS are presented.


Assuntos
Síndrome da Deleção 22q11/epidemiologia , Síndrome da Deleção 22q11/patologia , Doenças da Glândula Tireoide/epidemiologia , Doenças da Glândula Tireoide/patologia , Síndrome da Deleção 22q11/complicações , Adolescente , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Ontário/epidemiologia , Prevalência , Estudos Retrospectivos , Doenças da Glândula Tireoide/etiologia
9.
Pediatr Int ; 56(4): 462-6, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-24980921

RESUMO

Constitutional t(11;22)(q23;q11) is the most frequent recurrent non-Robertsonian translocation in humans. Balanced carriers of t(11;22) usually manifest no clinical symptoms, and are often identified after the birth of offspring with an unbalanced form of this translocation, known as Emanuel syndrome. To determine the prevalence of the disorder, we sent surveillance questionnaires to 735 core hospitals in Japan. The observed number of Emanuel syndrome cases was 36 and that of t(11;22) balanced translocation carriers, 40. On the basis of the de novo t(11;22) translocation frequency in sperm from healthy men, we calculated the frequency of the translocations in the general population. Accordingly, the prevalence of Emanuel syndrome was estimated at 1 in 110,000. Based on this calculation, the estimated number of Emanuel syndrome cases in Japan is 1063 and of t(11;22) balanced translocation carriers, 16,604, which are much higher than the numbers calculated from the questionnaire responses. It is possible that this discordance is partly attributable to a lack of disease identification. Further efforts should be made to increase the awareness of Emanuel syndrome to ensure a better quality of life for affected patients and their families.


Assuntos
Transtornos Cromossômicos/epidemiologia , Fissura Palatina/epidemiologia , Cardiopatias Congênitas/epidemiologia , Deficiência Intelectual/epidemiologia , Hipotonia Muscular/epidemiologia , Biologia Computacional , Monitoramento Epidemiológico , Feminino , Humanos , Japão/epidemiologia , Masculino , Prevalência , Inquéritos e Questionários
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