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1.
Cleft Palate Craniofac J ; : 10556656241234804, 2024 Feb 29.
Artigo em Inglês | MEDLINE | ID: mdl-38425129

RESUMO

OBJECTIVE: Identify and describe factors associated with retention and attrition of patients during longitudinal follow-up at multidisciplinary cleft clinic. DESIGN: Retrospective cohort study. SETTING: Single, tertiary care center. PATIENTS, PARTICIPANTS: Patients born between 1995 and 2007 with a diagnosis of cleft palate with or without cleft lip attending multidisciplinary cleft clinic. INTERVENTIONS: None tested, observational study. MAIN OUTCOME MEASURE(S): Age at last clinical appointment with a multidisciplinary cleft team provider. Attrition was defined as absence of an outpatient appointment following 15 years of age. RESULTS: Six hundred seventy-eight patients were included. The average age at last appointment across the entire cohort was 13.1 years (IQR 6.6-17.2). Patients who were Black (HR 1.60, 95% CI 1.10-2.32, p = 0.014) and other races (HR 1.90, 95% CI 1.22-2.98, p = 0.004) were more likely to be lost to follow-up compared to white patients. Publicly insured patients were more likely to experience attrition than those who were privately insured (HR 1.30, 95% CI 1.03-1.65, p = 0.030). Estimated income was not significantly associated with length of follow-up (p = 0.259). Those whose residence was in the fourth quartile of driving distance from our center experienced loss to follow-up significantly more than those who lived the closest (HR 2.04, 95% CI 1.50-2.78, p < 0.001). CONCLUSIONS: There is a high degree of follow-up attrition among patients with cleft lip and palate. Race, insurance status, and driving distance to our center were associated with attrition in a large, retrospective cohort of patients who have reached the age of cleft clinic graduation.

2.
Medicina (Kaunas) ; 60(1)2024 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-38256387

RESUMO

Background and Objectives: Axillary tissue hypertrophy consists of ectopic breast tissue and occurs in up to six percent of women. Women complain of pain, interference with activity, and dissatisfaction with appearance. While it is recommended that accessory breast tissue be removed via surgical excision, there is lack of consensus on the best technique for the surgical management of axillary tissue hypertrophy. In this study, the senior authors (BC and NT) review outcomes and complications as they pertain to the surgical treatment of axillary tissue hypertrophy and axillary contouring. Materials and Methods: A retrospective review of all patients (n = 35), from two separate institutions, who presented with axillary tissue hypertrophy between December 2019 and August 2021 was conducted. All patients underwent a technique that included direct crescentic dermato-lipectomy and glandular excision with axillary crease obliteration. Tissue was sent for histological analysis after removal. During a six-month follow-up period, all patient outcomes were recorded. Results: The authors treated 35 women with axillary tissue hypertrophy. All patients complained of aesthetic deformity with significant discomfort leading to the desire for surgery. Histologically, all specimens contained benign breast and adipose tissue. Hypertrophic scarring, seroma, and axillary cording were noted complications. Conclusions: Detailed is the surgical management and optimal technique that can be used to treat both adipose and fibroglandular axillary tissue hypertrophy while simultaneously providing a favorable axillary aesthetic.


Assuntos
Abdominoplastia , Obesidade , Humanos , Feminino , Hipertrofia/cirurgia , Tecido Adiposo , Estética
3.
Am J Prev Med ; 66(2): 195-204, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38010238

RESUMO

INTRODUCTION: Firearm-related injuries are among the five leading causes of death for people aged 1-44 years in the U.S. The immediate and long-term harms of firearm injuries pose an economic burden on society. Fatal and nonfatal firearm injury costs in the U.S. were estimated providing up-to-date economic burden estimates. METHODS: Counts of nonfatal firearm injuries were obtained from the 2019-2020 Healthcare Cost and Utilization Project Nationwide Emergency Department Sample. Data on nonfatal injury intent were obtained from the National Electronic Injury Surveillance System - Firearm Injury Surveillance System. Counts of deaths (firearm as underlying cause) were obtained from the 2019-2020 multiple cause-of-death mortality data from the National Vital Statistics System. Analyses were conducted in 2023. RESULTS: The total cost of firearm related injuries and deaths in the U.S. for 2020 was $493.2 billion, a 16 percent increase compared with 2019. There are significant disparities in the cost of firearm deaths in 2019-2020, with non-Hispanic Black people, males, and young and middle-aged groups being the most affected. CONCLUSIONS: Most of the nonfatal firearm injury-related costs are attributed to hospitalization. These findings highlight the racial/ethnic differences in fatal firearm injuries and the disproportionate cost burden to urban areas. Addressing this important public health problem can help ameliorate the costs to our society from the rising rates of firearm injuries.


Assuntos
Armas de Fogo , Ferimentos por Arma de Fogo , Pessoa de Meia-Idade , Masculino , Humanos , Estados Unidos/epidemiologia , Ferimentos por Arma de Fogo/epidemiologia , Vigilância da População , Saúde Pública , Custos de Cuidados de Saúde
4.
Aesthet Surg J ; 44(4): 347-353, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-37930673

RESUMO

Facial feminization surgery (FFS) is a form of gender-affirming care for the transgender population that is currently a highly debated topic both inside and outside of the medical community. Currently, a paucity of information is available in plastic surgery literature on ethical issues surrounding FFS. In this paper, we discuss 5 major ethical considerations for plastic surgeons with regard to FFS: (1) how society's changing view of gender has impacted the importance of FFS; (2) whether FFS is medically necessary and should be covered by insurance; (3) to what extent resources should be invested in removing barriers to access FFS; (4) how patient selection criteria should address the irreversibility of the procedure and age of consent; and (5) how femininity and beauty standards contribute to each other and whether they can be disentangled. This paper aims to analyze the arguments made for and against each of these 5 nuanced issues and to expand these debates from the theoretical to the practical by suggesting approaches for reconciliation.


Assuntos
Procedimentos de Cirurgia Plástica , Cirurgia Plástica , Pessoas Transgênero , Transexualidade , Masculino , Feminino , Humanos , Feminização/cirurgia , Transexualidade/cirurgia
5.
Plast Reconstr Surg ; 153(1): 181e-193e, 2024 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-38127451

RESUMO

LEARNING OBJECTIVES: After studying this article, the participant should be able to: 1. Understand the regional anatomy involved in facial feminization surgery, the key differences between the male and female face, and surgical approaches for modification. 2. Appreciate the integration of preoperative virtual planning and nonoperative approaches for facial feminization care. 3. Understand the perioperative process and potential complications and sequela. 4. Understand the importance of transgender care acceptance as it pertains to clinical outcomes. SUMMARY: Facial feminization surgery (FFS) is composed of a broad spectrum of gender-affirming surgical procedures with the goal of modifying specific facial features to create a more feminine appearance. As FFS continues to evolve as a subspecialty of transgender care, it is important to consider the psychosocial evaluation, evolving aesthetic tastes, nonoperative facial feminization care, preoperative virtual planning, specialized instrumentation, and potential complications/sequelae when performing these procedures. Computed tomographic imaging and virtual preoperative planning may be used to assist the surgeon with morphologic typing of the brow, supraorbital rim, chin, and lateral mandible regions and aid in performing safer, more efficient procedures. The increasing number of FFS procedures performed on transwomen annually has been supported by objective outcome studies that demonstrate progress in minimizing both misgendering in social environments and reducing dysphoric feelings.


Assuntos
Pessoas Transgênero , Transexualidade , Humanos , Masculino , Feminino , Face/cirurgia , Feminização/cirurgia , Transexualidade/cirurgia , Pessoas Transgênero/psicologia , Assistência Perioperatória
6.
Artigo em Inglês | MEDLINE | ID: mdl-38062889

RESUMO

BACKGROUND: The aim of many interventions used by speech and language therapists (SLTs) is to change behaviours related to communication and interaction. Parent-led language interventions for children in the early years (0-5 years) rely on SLTs supporting parents to change their behaviour in child-focused interactions to effect a change in the child's communication. Therapeutic techniques used by SLTs in parent-led language interventions are largely underspecified, impacting on intervention reporting, replication, trialling and development. The Behaviour Change Technique Taxonomy Version 1 (BCTTv1) offers a method of describing intervention techniques developed for use in public health interventions, but with several examples of its application to speech and language interventions. AIMS: To identify behaviour change techniques (BCTs) from the BCTTv1 occurring in parent-led language interventions for children in the early years. METHODS & PROCEDURES: A literature search identified relevant descriptions of parent-led language interventions. These were coded using the BCTTv1. A reliability check was carried out on 10% of the descriptions. To confirm the use of identified BCTs in clinical practice, results of the literature search were triangulated with an online survey of SLTs, and observations of SLTs delivering parent-led language intervention. OUTCOMES & RESULTS: A total of 84 papers containing descriptions of 45 interventions were coded; 62 SLTs responded to the survey and three SLTs were observed delivering parent-led language intervention. A total of 24 BCTs were identified in the literature search, replicated in the observations and verified by SLTs in the survey. BCTs were identified at two levels: Level 1 SLT implemented to change parent interactive behaviour; and Level 2 parent implemented to change child communicative behaviour. CONCLUSIONS & IMPLICATIONS: The BCTTv1 is a useful starting place for describing parent-led language interventions. With some additions and adjustments, BCTs identified in this study were immediately recognized by practitioners and can easily be adopted into practice. WHAT THIS PAPER ADDS: What is already known on this subject Techniques used in SLT interventions are often not clearly described. The BCTTv1 has been used to clarify technique descriptions with success in a small number of SLT disciplines, but not yet in parent-led language interventions for preschoola children. What this paper adds to the existing knowledge This paper constitutes the first research into quantifying the techniques used in parent-led language interventions using the BCTTv1. What are the potential or actual clinical implications of this work? This paper provides a clear list of techniques used by SLTs implementing interventions for preschool children, which can be immediately adopted and used in practice. It also highlights potential adjustments and gaps in the BCTTv1 in relation to SLT which can contribute to future iterations.

7.
Medicina (Kaunas) ; 59(12)2023 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-38138173

RESUMO

Facial Feminization Surgery (FFS) is a transformative surgical approach aimed at aligning the facial features of transgender women with their gender identity. Through a systematic analysis, this paper explores the clinical differences between male and female facial skeletons along with the craniofacial techniques employed in FFS for each region. The preoperative planning stage is highlighted, emphasizing the importance of virtual planning and AI morphing as valuable tools to be used to achieve surgical precision. Consideration is given to special circumstances, such as procedure sequencing for older patients and silicone removal. Clinical outcomes, through patient-reported outcome measures and AI-based gender-typing assessments, showcase the efficacy of FFS in achieving proper gender recognition and alleviating gender dysphoria. This comprehensive review not only offers valuable insights into the current state of knowledge regarding FFS but also emphasizes the potential of artificial intelligence in outcome evaluation and surgical planning to further advance patient care and satisfaction with FFS.


Assuntos
Feminização , Transexualidade , Humanos , Feminino , Masculino , Feminização/cirurgia , Inteligência Artificial , Identidade de Gênero , Face/cirurgia , Transexualidade/cirurgia
9.
J Mol Diagn ; 25(7): 524-531, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37088140

RESUMO

Genome sequencing (GS) is a powerful clinical tool used for the comprehensive diagnosis of germline disorders. GS library preparation typically involves mechanical DNA fragmentation, end repair, and bead-based library size selection followed by adapter ligation, which can require a large amount of input genomic DNA. Tagmentation using bead-linked transposomes can simplify the library preparation process and reduce the DNA input requirement. Here we describe the clinical validation of tagmentation-based PCR-free GS as a clinical test for rare germline disorders. Compared with the Genome-in-a-Bottle Consortium benchmark variant sets, GS had a recall >99.7% and a precision of 99.8% for single nucleotide variants and small insertion-deletions. GS also exhibited 100% sensitivity for clinically reported sequence variants and the copy number variants examined. Furthermore, GS detected mitochondrial sequence variants above 5% heteroplasmy and showed reliable detection of disease-relevant repeat expansions and SMN1 homozygous loss. Our results indicate that while lowering DNA input requirements and reducing library preparation time, GS enables uniform coverage across the genome as well as robust detection of various types of genetic alterations. With the advantage of comprehensive profiling of multiple types of genetic alterations, GS is positioned as an ideal first-tier diagnostic test for germline disorders.


Assuntos
DNA , Doenças Raras , Humanos , Sequência de Bases , Mapeamento Cromossômico , Análise de Sequência de DNA/métodos , Biblioteca Gênica , Sequenciamento de Nucleotídeos em Larga Escala/métodos
11.
Ann Plast Surg ; 90(6S Suppl 5): S607-S611, 2023 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-36752405

RESUMO

INTRODUCTION: Surgical advancements in breast reconstruction have allowed a shift toward optimizing patient-reported outcomes and efficiency measures. The enhanced recovery after surgery (ERAS) protocol has been instrumental in improving outcomes, but the effect of these protocols on health care spending has not been examined. This study aims to assess the effect of ERAS protocols on the length of hospital stay and costs associated with microsurgical breast reconstruction. METHODS: In 2018, the authors implemented an ERAS protocol for patients undergoing microsurgical breast reconstruction that included perioperative procedures involving patient education and care. Subjects included patients who underwent deep inferior epigastric perforator flap breast reconstruction at the authors' institution between 2016 and 2019. Data were gathered from the electronic medical record and the hospital system's finance department, and patients were divided into pre-ERAS and ERAS cohorts. A 2-sample t test was used for statistical analysis. RESULTS: The study included 269 patients with no statistically significant differences in demographic data between the cohorts. The average length of hospitalization was 3.46 days for the pre-ERAS group and 2.45 days for the ERAS group ( P = 0.000). In a linear regression, the ERAS protocol predicted a 1.04-day decrease in the length of stay ( P = 0.000). Overall, total direct cost decreased by 7.5% with the ERAS protocol. CONCLUSION: The rising cost of health care presents a challenge for providers to reduce the cost burden placed on our health system while providing the highest-quality care. This study demonstrates that the use of standardized ERAS protocols can achieve this 2-fold goal.


Assuntos
Recuperação Pós-Cirúrgica Melhorada , Custos de Cuidados de Saúde , Mamoplastia , Humanos , Custos e Análise de Custo , Tempo de Internação , Mamoplastia/economia , Procedimentos de Cirurgia Plástica , Complicações Pós-Operatórias , Estudos Retrospectivos
12.
Clin Plast Surg ; 50(2): 337-346, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36813411

RESUMO

There are numerous indications for hybrid breast reconstruction, with the most common being patients who have inadequate donor site volume to achieve the desired breast volume. This article reviews all aspects of hybrid breast reconstruction, including preoperative and assessment, operative technique and considerations, and postoperative management.


Assuntos
Neoplasias da Mama , Mamoplastia , Retalho Perfurante , Humanos , Feminino , Mastectomia/métodos , Mamoplastia/métodos , Estudos Retrospectivos
13.
Plast Reconstr Surg ; 152(3): 682-690, 2023 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-36692502

RESUMO

BACKGROUND: Improving perioperative efficiency helps reduce unnecessary surgical expenditure, increase operating room throughput, improve patient safety, and enhance staff and patient satisfaction. Lean Six Sigma (LSS) is a quality improvement model that has been successfully applied to eliminate inefficiencies in the business sector but has not yet been widely adopted in medicine. This study investigates the adaptation of LSS to improve operative efficiency for plastic surgery procedures. METHODS: The authors followed the define, measure, analyze, improve, and control phases to implement LSS. The key outcome measures gathered were operative times, including the cut-to-close time, and the total time the patient spent in the operating room. RESULTS: The study included a total of 181 patients who underwent immediate bilateral deep inferior epigastric perforator flap breast reconstruction between January of 2016 and December of 2019. The LSS interventions were associated with a decrease in total operative time from 636.36 minutes to 530.35 minutes, and a decrease in the time between incision to closure from 555.16 minutes to 458.85 minutes for a bilateral mastectomy with immediate deep inferior epigastric artery flap breast reconstruction. CONCLUSIONS: This study demonstrates that LSS is useful to improve perioperative efficiency during complex plastic surgery procedures. The workflow of the procedure was improved by determining the optimal spatial positioning and distinct roles for each surgeon and preparing surgeon-specific surgical trays. Two process maps were developed to visualize the positioning of the surgeons during each stage of the procedure and depict the parallel workflow that helped improve intraoperative efficiency.


Assuntos
Neoplasias da Mama , Salas Cirúrgicas , Humanos , Feminino , Eficiência Organizacional , Gestão da Qualidade Total , Mastectomia , Melhoria de Qualidade
14.
Inj Prev ; 29(1): 91-100, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36600522

RESUMO

CONTEXT: Costs related to criminal justice are an important component of the economic burden of injuries; such costs could include police involvement, judicial and corrections costs, among others. If the literature has sufficient information on the criminal justice costs related to injury, it could be added to existing estimates of the economic burden of injury. OBJECTIVE: To examine research on injury-related criminal justice costs, and what extent cost information is available by type of injury. DATA SOURCES: Medline, PsycINFO, Sociological Abstracts ProQuest, EconLit and National Criminal Justice Reference Service were searched from 1998 to 2021. DATA EXTRACTION: Preferred Reporting Items for Systematic reviews and Meta-Analyses was followed for data reporting. RESULTS: Overall, 29 studies reported criminal justice costs and the costs of crime vary considerably. CONCLUSIONS: This study illustrates possible touchpoints for cost inputs and outputs in the criminal justice pathway, providing a useful conceptualisation for better estimating criminal justice costs of injury in the future. However, better understanding of all criminal justice costs for injury-related crimes may provide justification for prevention efforts and potentially for groups who are disproportionately affected. Future research may focus on criminal justice cost estimates from injuries by demographics to better understand the impact these costs have on particular populations.


Assuntos
Crime , Direito Penal , Humanos , Polícia
15.
Mol Cancer Res ; 21(5): 411-427, 2023 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-36669126

RESUMO

The nuclear deubiquitylase BRCA1-associated protein 1 (BAP1) is frequently inactivated in malignant pleural mesothelioma (MPM) and germline BAP1 mutation predisposes to cancers including MPM. To explore the influence on cell physiology and drug sensitivity, we sequentially edited a predisposition mutation (w-) and a promoter trap (KO) into human mesothelial cells. BAP1w-/KO MeT5A cells express less BAP1 protein and phenocopy key aspects of BAP1 loss in MPM. Stable isotope labeling with amino acids in cell culture-mass spectrometry revealed evidence of metabolic adaptation, with concomitant alteration of cellular metabolites. In MeT5A, BAP1 deficiency reduces glycolytic enzyme levels but increases enzymes involved in the tricarboxylic acid cycle and anaplerotic pathways. Notably both argininosuccinate synthase 1 (ASS1), essential for cellular synthesis of arginine, and its substrate aspartate, are elevated in BAP1w-/KO MeT5A cells. Likewise, ASS1 expression is higher in BAP1-altered MPM cell lines, and inversely correlates with BAP1 in The Cancer Genome Atlas MESO dataset. Elevated ASS1 is also evident by IHC staining in epithelioid MPM lacking nuclear BAP1 expression, with improved survival among patients with BAP1-negative/ASS1-expressing tumors. Alterations in arginine metabolism may sensitize cells to metabolic drugs and we find that BAP1-negative/ASS1-expressing MPM cell lines are more sensitive to ASS1 inhibition, although not to inhibition of purine synthesis by mizoribine. Importantly, BAP1w-/KO MeT5A become desensitized to arginine deprivation by pegylated arginine deiminase (ADI-PEG20), phenocopying BAP1-negative/ASS1-expressing MPM cell lines. IMPLICATIONS: Our data reveal an interrelationship between BAP1 and arginine metabolism, providing a potential means of identifying patients with epithelioid MPM likely to benefit from ADI-PEG20.


Assuntos
Mesotelioma Maligno , Mesotelioma , Humanos , Argininossuccinato Sintase/genética , Argininossuccinato Sintase/metabolismo , Ubiquitina Tiolesterase/genética , Aminoácidos , Arginina/metabolismo , Mesotelioma/tratamento farmacológico , Mesotelioma/genética , Linhagem Celular Tumoral , Proteínas Supressoras de Tumor/genética
16.
Cancers (Basel) ; 14(23)2022 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-36497318

RESUMO

Malignant pleural mesothelioma (MPM) has limited treatment options and poor prognosis. Frequent inactivation of the tumour suppressors BAP1, NF2 and P16 may differentially sensitise tumours to treatments. We have established chick chorioallantoic membrane (CAM) xenograft models of low-passage MPM cell lines and protocols for evaluating drug responses. Ten cell lines, representing the spectrum of histological subtypes and tumour suppressor status, were dual labelled for fluorescence/bioluminescence imaging and implanted on the CAM at E7. Bioluminescence was used to assess viability of primary tumours, which were excised at E14 for immunohistological staining or real-time PCR. All MPM cell lines engrafted efficiently forming vascularised nodules, however their size, morphology and interaction with chick cells varied. MPM phenotypes including local invasion, fibroblast recruitment, tumour angiogenesis and vascular remodelling were evident. Bioluminescence imaging could be used to reliably estimate tumour burden pre- and post-treatment, correlating with tumour weight and Ki-67 staining. In conclusion, MPM-CAM models recapitulate important features of the disease and are suitable to assess drug targets using a broad range of MPM cell lines that allow histological or genetic stratification. They are amenable to multi-modal imaging, potentially offering a time and cost-efficient, 3Rs-compliant alternative to rodent xenograft models to prioritise candidate compounds from in vitro studies.

18.
Plast Reconstr Surg ; 150(6): 1368-1374, 2022 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-36161794

RESUMO

BACKGROUND: The growth of social media has transformed advertising within plastic surgery. Recent studies have characterized these developments, but objective analysis is needed. METHODS: This is a cross-sectional analysis of online media use by American Society of Plastic Surgeons members who received board certification in 2000, 2005, 2010, 2015, or 2019. Online searches and StatShow revealed social media and website metrics. Metropolitan-based practices were determined using Department of Agriculture continuum codes. Descriptive and quantitative analyses were used to make inferences regarding study aims. RESULTS: This study included 811 surgeons. A total of 58.6 percent had practice websites and 43.9 percent had professional Instagram accounts. Instagram use was widespread across subspecialties and there was no significant difference in the number of followers by subspecialty ( p = 0.34). Year of certification had no significant effect on the number of followers ( p = 0.12); however, recently certified and seasoned members had the fewest. The top 1 percent of surgeons had more followers than the remaining 99 percent combined. Those with metropolitan-based practices had significantly higher website traffic ( p = 0.01) but no difference in the number of followers ( p = 0.88). There was no evidence that the number of followers or posts per month correlated with website traffic ( R 2 = 0.004 and 0.036, respectively). CONCLUSIONS: The study demonstrates findings from a cross-sectional analysis of plastic surgeons from different training backgrounds, regions, and tenure. The use of Instagram in professional practice is widespread but there is no correlation between its use and increased website traffic.


Assuntos
Procedimentos de Cirurgia Plástica , Mídias Sociais , Cirurgiões , Cirurgia Plástica , Humanos , Estados Unidos , Cirurgia Plástica/educação , Estudos Transversais
19.
Genet Med ; 24(7): 1583-1591, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35499524

RESUMO

PURPOSE: CTR9 is a subunit of the PAF1 complex (PAF1C) that plays a crucial role in transcription regulation by binding CTR9 to RNA polymerase II. It is involved in transcription-coupled histone modification through promoting H3K4 and H3K36 methylation. We describe the clinical and molecular studies in 13 probands, harboring likely pathogenic CTR9 missense variants, collected through GeneMatcher. METHODS: Exome sequencing was performed in all individuals. CTR9 variants were assessed through 3-dimensional modeling of the activated human transcription complex Pol II-DSIF-PAF-SPT6 and the PAF1/CTR9 complex. H3K4/H3K36 methylation analysis, mitophagy assessment based on tetramethylrhodamine ethyl ester perchlorate immunofluorescence, and RNA-sequencing in skin fibroblasts from 4 patients was performed. RESULTS: Common clinical findings were variable degrees of intellectual disability, hypotonia, joint hyperlaxity, speech delay, coordination problems, tremor, and autism spectrum disorder. Mild dysmorphism and cardiac anomalies were less frequent. For 11 CTR9 variants, de novo occurrence was shown. Three-dimensional modeling predicted a likely disruptive effect of the variants on local CTR9 structure and protein interaction. Additional studies in fibroblasts did not unveil the downstream functional consequences of the identified variants. CONCLUSION: We describe a neurodevelopmental disorder caused by (mainly) de novo variants in CTR9, likely affecting PAF1C function.


Assuntos
Transtorno do Espectro Autista , Deficiência Intelectual , Transtornos do Neurodesenvolvimento , Fosfoproteínas , Fatores de Transcrição , Regulação da Expressão Gênica , Heterozigoto , Humanos , Deficiência Intelectual/genética , Transtornos do Neurodesenvolvimento/genética , Fosfoproteínas/genética , Fatores de Transcrição/genética
20.
NPJ Genom Med ; 7(1): 27, 2022 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-35395838

RESUMO

Whole genome sequencing (WGS) shows promise as a first-tier diagnostic test for patients with rare genetic disorders. However, standards addressing the definition and deployment practice of a best-in-class test are lacking. To address these gaps, the Medical Genome Initiative, a consortium of leading health care and research organizations in the US and Canada, was formed to expand access to high quality clinical WGS by convening experts and publishing best practices. Here, we present best practice recommendations for the interpretation and reporting of clinical diagnostic WGS, including discussion of challenges and emerging approaches that will be critical to harness the full potential of this comprehensive test.

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