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BMC Medical Genomics Aug 2023Short stature is a common human trait. More severe and/or associated short stature is usually part of the presentation of a syndrome and may be a monogenic disease. The...
BACKGROUND
Short stature is a common human trait. More severe and/or associated short stature is usually part of the presentation of a syndrome and may be a monogenic disease. The present study aimed to identify the genetic etiology of children with short stature of unknown origin.
METHODS
A total of 232 children with short stature of unknown origin from March 2013 to May 2020 were enrolled in this study. Whole exome sequencing (WES) was performed for the enrolled patients to determine the underlying genetic etiology.
RESULTS
We identified pathogenic or likely pathogenic genetic variants in 18 (7.8%) patients. All of these variants were located in genes known to be associated with growth disorders. Five of the genes are associated with paracrine signaling or cartilage extracellular matrix in the growth plate, including NPR2 (N = 1), ACAN (N = 1), CASR (N = 1), COMP (N = 1) and FBN1 (N = 1). Two of the genes are involved in the RAS/MAPK pathway, namely, PTPN11 (N = 6) and NF1 (N = 1). Two genes are associated with the abnormal growth hormone-insulin-like growth factor 1 (GH-IGF1) axis, including GH1 (N = 1) and IGF1R (N = 1). Two mutations are located in PROKR2, which is associated with gonadotropin-releasing hormone deficiency. Mutations were found in the remaining two patients in genes with miscellaneous mechanisms: ANKRD11 (N = 1) and ARID1A (N = 1).
CONCLUSIONS
The present study identified pathogenic or likely pathogenic genetic variants in eighteen of the 232 patients (7.8%) with short stature of unknown origin. Our findings suggest that in the absence of prominent malformation, genetic defects in hormones, paracrine factors, and matrix molecules may be the causal factors for this group of patients. Early genetic testing is necessary for accurate diagnosis and precision treatment.
Topics: Humans; Child; Dwarfism; Growth Disorders; Genetic Testing; Mutation
PubMed: 37605180
DOI: 10.1186/s12920-023-01626-4 -
Journal of Neuromuscular Diseases 2024This report summarizes the key discussions from the "Early Care (0-3 years) in Duchenne Muscular Dystrophy" meeting, which aimed to address the challenges and...
OBJECTIVE
This report summarizes the key discussions from the "Early Care (0-3 years) in Duchenne Muscular Dystrophy" meeting, which aimed to address the challenges and opportunities in the diagnosis and care of Duchenne muscular dystrophy (DMD) and female carriers within the 0-3-year age group.
METHODS
The meeting brought together experts and healthcare providers who shared insights, discussed advancements in DMD care, and identified research needs. Presentations covered diagnostic challenges, approved therapies, clinical trials, identification of young female carriers, and the importance of clinical care and support for families.
RESULTS
The meeting highlighted the importance of timely diagnosis and the lack of evidence-based guidelines for the care of children with DMD aged 0-3 years. Diagnostic challenges were discussed, including delays in receiving a DMD diagnosis and disparities based on ethnicity. The potential benefits and process of newborn screening were addressed.Approved therapeutic interventions, such as corticosteroids and exon-skipping drugs, were explored, with studies indicating the potential benefits of early initiation of corticosteroid therapy and the safety of exon-skipping drugs in DMD. Clinical trials involving infants and young boys were discussed, focusing on drugs like ataluren, vamorolone, and gene therapies.The meeting emphasized the importance of clinical care and support for families, including comprehensive information provision, early intervention services, and individualized support. The identification and care of young female carriers were also addressed.
CONCLUSION
The meeting provided a platform for experts and healthcare providers to discuss and identify key aspects of early care for children with DMD aged 0-3 years. The meeting emphasized the need for early diagnosis, evidence-based guidelines, and comprehensive care and support for affected children and their families. Further research, collaboration, and the development of consensus guidelines are needed to improve early diagnosis, treatment, and outcomes in this population.
Topics: Child, Preschool; Female; Humans; Infant; Infant, Newborn; Male; Adrenal Cortex Hormones; Muscular Dystrophy, Duchenne; Neonatal Screening
PubMed: 38189762
DOI: 10.3233/JND-230180 -
Revista Brasileira de Ginecologia E... Sep 2023
Topics: Humans; Female; Breast Neoplasms; Early Detection of Cancer; Mammography; Mass Screening
PubMed: 37846189
DOI: 10.1055/s-0043-1775931 -
Revista Brasileira de Ginecologia E... Oct 2023
Topics: Humans; Female; Breast Neoplasms; Early Detection of Cancer; Mammography; Mass Screening
PubMed: 37944930
DOI: 10.1055/s-0043-1776716 -
PloS One 2023Diagnostic network optimization (DNO) is an analytical approach that enables use of available country data to inform evidence-based decision-making to optimize access to...
Optimizing diagnostic networks to increase patient access to TB diagnostic services: Development of the diagnostic network optimization (DNO) approach and learnings from its application in Kenya, India and the Philippines.
Diagnostic network optimization (DNO) is an analytical approach that enables use of available country data to inform evidence-based decision-making to optimize access to diagnostic services. A DNO methodology was developed using available data sources and a commercial supply chain optimization software. In collaboration with Ministries of Health and partners, the approach was applied in Kenya, India and the Philippines to map TB diagnostic networks, identify misalignments, and determine optimal network design to increase patient access to TB diagnostic services and improve device utilization. The DNO analysis was successfully applied to evaluate and inform TB diagnostic services in Kenya, India and the Philippines as part of national strategic planning for TB. The analysis was tailored to each country's specific objectives and allowed evaluation of factors such as the number and placement of different TB diagnostics, design of sample referral networks and integration of early infant diagnosis for HIV at national and sub-national levels and across public and private sectors. Our work demonstrates the value of DNO as an innovative approach to analysing and modelling diagnostic networks, particularly suited for use in low-resource settings, as an open-access approach that can be applied to optimize networks for any disease.
Topics: Humans; Philippines; Kenya; Referral and Consultation; Diagnostic Services; India
PubMed: 38033120
DOI: 10.1371/journal.pone.0279677 -
Journal of Medical Genetics Dec 2023Multigene panel testing by next-generation sequencing (MGP-NGS) enables the detection of germline pathogenic or likely pathogenic variants (PVs/LPVs) in genes beyond...
BACKGROUND
Multigene panel testing by next-generation sequencing (MGP-NGS) enables the detection of germline pathogenic or likely pathogenic variants (PVs/LPVs) in genes beyond those associated with a certain cancer phenotype. Opportunistic genetic screening based on MGP-NGS in patients with suspicion of hereditary cancer reveals these incidental findings (IFs).
METHODS
MGP-NGS was performed in patients who fulfilled the clinical criteria to undergo genetic testing according to the Catalan Health Service guidelines. Variants were classified following the American College of Medical Genetics and Genomics-Association for Molecular Pathology guidelines and the Cancer Variant Interpretation Group UK guidelines.
RESULTS
IFs were identified in 10 (1.22%) of the 817 patients who underwent MGP-NGS. The mean age at cancer diagnosis was 49.4±9.5 years. Three IFs (30.0%) were detected in , two (20.0%) in and and one (10.0%) in and . Seven (70.0%) IFs were single-nucleotide substitutions, two (20.0%) were deletions and one (10.0%) was a duplication. Three (30.0) IFs were located in intronic regions, three (30.3%) were nonsense, two (20.0%) were frameshift and two (20.0%) were missense variations. Six (60.0%) IFs were classified as PVs and four (40.0%) as LPVs.
CONCLUSIONS
Opportunistic genetic screening increased the diagnostic yield by 1.22% in our cohort. Most of the identified IFs were present in clinically actionable genes (n=7; 70.0%), providing these families with an opportunity to join cancer early detection programmes, as well as secondary cancer prevention. IFs might facilitate the diagnosis of asymptomatic individuals and the early management of cancer once it develops.
Topics: Humans; Adult; Middle Aged; Early Detection of Cancer; Genetic Testing; Neoplasms; Phenotype; Genetic Predisposition to Disease; Germ-Line Mutation
PubMed: 37591735
DOI: 10.1136/jmg-2023-109389 -
Zhejiang Da Xue Xue Bao. Yi Xue Ban =... Dec 2023Newborn screening (NBS) plays a significant role in reducing the risk of birth defects. NBS in China began in the early 1980s. Under the protection of laws and...
Newborn screening (NBS) plays a significant role in reducing the risk of birth defects. NBS in China began in the early 1980s. Under the protection of laws and regulations and the leadership of the national health administration, approved screening centers in public hospitals took the responsibility for publicity, screening, diagnosis, treatment, follow-up and management of birth defects. As of 2022, 31 provinces (autonomous regions and municipalities directly under the central government) have carried out NBS for phenylketonuria, congenital hypothyroidism, and hearing loss, 23 provinces have carried out screening for glucose-6-phosphate dehydrogenase (with a screening rate of 89.24%), and 24 provinces have carried out screening for congenital adrenal cortical hyperplasia (91.45% screening rate). Over the past four decades, screening techniques have evolved from bacterial inhibition, fluorescence analysis, and tandem mass spectrometry for the detection of biochemical markers to genetic testing, which has greatly contributed to the expansion of the types of diseases screened for. The combined use of metabolomics and genomics is currently being explored. Effective management and rigorous quality control of NBS are prerequisites for improving the quality and ensuring the accuracy of screening. The Quality Management System for Newborn Screening System Network (QMS-NBS), established by the National Center for Clinical Laboratories, covers all screening centers and related blood collection agencies. The operation of the QMS-NBS allows the quality and performance of screening to be transparent and measurable, ensuring the quality and efficiency of screening. This article provides an overview of the history of NBS, especially the evolution of policies for the NBS in China, the construction of screening institutions, the number of newborns screened, the incidence rates of screened diseases, the changes in screening technology, the expansion of new diseases screened for, and the quality control of NBS. Overall, the progress in NBS in China has not only benefited from the development and standardization at the technological level, but also benefited from the construction of policies, regulations and ethics.
Topics: Infant, Newborn; Humans; Neonatal Screening; Phenylketonurias; Genetic Testing; Congenital Hypothyroidism; China
PubMed: 38115737
DOI: 10.3724/zdxbyxb-2023-0467 -
PloS One 2023Predictive genetic testing can provide information about whether or not someone will develop or is likely to develop a specific condition at a later stage in life.... (Review)
Review
Predictive genetic testing can provide information about whether or not someone will develop or is likely to develop a specific condition at a later stage in life. Economic evaluation can assess the value of money for such testing. Studies on the economic evaluation of predictive genetic testing have been carried out in a variety of settings, and this research aims to conduct a scoping review of findings from these studies. We searched the PubMed, Web of Science, Embase, and Cochrane databases with combined search terms, from 2019 to 2022. Relevant studies from 2013 to 2019 in a previous systematic review were also included. The study followed the recommended stages for undertaking a scoping review. A total of 53 studies were included, including 33 studies from the previous review and 20 studies from the search of databases. A significant number of studies focused on the US, UK, and Australia (34%, 23%, and 11%). The most frequently included health conditions were cancer and cardiovascular diseases (68% and 19%). Over half of the studies compared predictive genetic testing with no genetic testing, and the majority of them concluded that at least some type of genetic testing was cost-effective compared to no testing (94%). Some studies stated that predictive genetic testing is becoming more cost-effective with the trend of lowering genetic testing costs. Studies on predictive genetic testing covered various health conditions, particularly cancer and cardiovascular diseases. Most studies indicated that predictive genetic testing is cost-effective compared to no testing.
Topics: Humans; Cost-Benefit Analysis; Cardiovascular Diseases; Australia; Genetic Testing
PubMed: 37531363
DOI: 10.1371/journal.pone.0276572 -
BMC Medical Ethics Oct 2023Prenatal genetic testing, in particular non-invasive prenatal testing (NIPT), as well as screening for risks associated with pregnancy, and counseling, play pivotal...
BACKGROUND
Prenatal genetic testing, in particular non-invasive prenatal testing (NIPT), as well as screening for risks associated with pregnancy, and counseling, play pivotal roles in reproductive healthcare, offering valuable information about the health of the fetus to expectant parents. This study aims to delve into the perspectives and experiences of women considering genetic testing and screening during pregnancy, focusing on their decision-making processes and the implications for informed consent.
METHODS
A nationwide qualitative study was conducted in Switzerland, involving in-depth interviews with women who were 1 to 2 years post-partum, covered by basic compulsory Swiss insurance, including women with a migration background. Thematic analysis was employed to identify key themes and patterns in the data.
RESULTS
The findings underscore the significance of effective communication during prenatal counseling, suggesting that healthcare providers could not only convey technical information but also support women in their decision-making processes. Women need comprehensive information about genetic testing and its implications, as well as the reasons for screening during pregnancy, as there might be a need to bridge knowledge gaps and clarify misconceptions. Furthermore, the study highlights the multifaceted nature of decision-making, with women considering factors such as uncertainty, values, emotional responses, and societal support systems. The concept of acceptance emerged as a crucial theme, with some women expressing their readiness to love and accept their child, regardless of genetic anomalies or disabilities.
CONCLUSION
This study offers valuable insights into the perspectives and needs of women regarding prenatal genetic testing, screening, and counseling in Switzerland. It underscores the importance of enhancing the clinical interaction and informed consent process by providing comprehensive information, addressing misconceptions, and supporting women in decision-making about pregnancy management and the management of the child's health, following prenatal genetic testing, including NIPT. These findings can inform healthcare providers and policymakers in improving the quality of prenatal counseling, ensuring informed consent, and supporting women in making well-informed and meaningful decisions about genetic testing, and on the use of screening during pregnancy.
Topics: Pregnancy; Child; Female; Humans; Prenatal Diagnosis; Switzerland; Decision Making; Genetic Testing; Fetus
PubMed: 37872496
DOI: 10.1186/s12910-023-00964-3 -
BMC Health Services Research Jul 2023In Ghana, tuberculosis (TB) case detection is low (< 34%). Existing scientific evidence suggest access to TB diagnostic tests play an essential role in TB case...
BACKGROUND
In Ghana, tuberculosis (TB) case detection is low (< 34%). Existing scientific evidence suggest access to TB diagnostic tests play an essential role in TB case detection, yet little has been scientifically documented on it in Ghana. This study, therefore, sought to map TB diagnosis sites, and describe the geographic availability and physical accessibility to TB diagnosis in six regions of Ghana to inform scale-up and future placement of TB diagnostic tests.
METHODS
We assembled the geolocation and attribute data of all health facilities offering TB diagnosis in Upper West Region (UWR), Upper East Region (UER), Ahafo, North-East, Northern, and Savannah regions. QGIS was employed to estimate the distance and travel time to TB diagnosis sites within regions. Travel time estimates were based on assumed motorised tricycle speed of 20 km (km)/hour.
RESULTS
Of the total 1584 health facilities in the six regions, 86 (5.4%) facilities were providing TB diagnostic testing services. This 86 TB diagnosis sites comprised 56 (65%) microscopy sites, 23 (27%) both microscopy and GeneXpert sites, and 7 (8%) GeneXpert only sites (8%). Of the 86 diagnosis sites, 40 (46%) were in the UER, follow by Northern Region with 16 (19%), 12 (14%) in UWR, 9 (10%) in Ahafo Region, 5 (6%) in North East, and 4 (5%) in Savannah Region. The overall estimated mean distance and travel time to the nearest TB diagnosis site was 23.3 ± 13.8 km and 67.6 ± 42.6 min respectively. Savannah Region recorded the longest estimated mean distance and travel time with 36.1 ± 14.6 km and 108.3 ± 43.9 min, whilst UER recorded the shortest with 10.2 ± 5.8 km and 29.1 ± 17.4 min. Based on a 10 km buffer of settlement areas, an estimated 75 additional TB diagnosis sites will be needed to improve access to TB diagnosis services across the six regions.
CONCLUSION
This study highlights limited availability of TB diagnosis sites and poor physical accessibility to TB diagnosis sites across five out of the six regions. Targeted implementation of additional TB diagnosis sites is needed to reduce travel distances to ≤ 10 km.
Topics: Humans; Cross-Sectional Studies; Ghana; Tuberculosis; Diagnostic Services; Health Services Accessibility; Diagnostic Tests, Routine
PubMed: 37452305
DOI: 10.1186/s12913-023-09755-3