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BMC Pulmonary Medicine Nov 2022Obstructive sleep apnea (OSA) is a modifiable risk factor for acute coronary syndrome (ACS), with high prevalence but low diagnostic rates. Therefore, it is particularly...
The value of nurse-led anthropometric and oropharyngeal measurements combined with STOP-Bang questionnaire in screening for obstructive sleep apnea in patients with acute coronary syndrome: a prospective cohort study.
BACKGROUND
Obstructive sleep apnea (OSA) is a modifiable risk factor for acute coronary syndrome (ACS), with high prevalence but low diagnostic rates. Therefore, it is particularly important to develop strategies for better screening for OSA in newly admitted ACS patients.
METHODS
From March 2017 to October 2019, consecutive eligible patients with ACS underwent cardiorespiratory polygraphy during hospitalization. OSA was defined as an apnea-hypopnea index (AHI) ≥ 15 events/h. All anthropometric and oropharyngeal parameters are measured by specialist nurses.
RESULTS
Finally, 761 ACS patients were recruited in the present study. Prevalence of moderate/severe OSA was 53.2% based on diagnostic criteria of AHI ≥ 15. Correlation analysis illustrated that AHI was positively correlated with anthropometric characteristics. In the multivariate model, only micrognathia (OR 2.02, 95% CI 1.02-4.00, P = 0.044), waist circumference (OR 1.08, 95% CI 1.04-1.11, P < 0.001), and STOP-BANG Questionnaire (SBQ) score (OR 1.45, 95% CI 1.27-1.66, P < 0.001) were independently associated with the prevalence of OSA. Receiver operating characteristic curve (ROC) analysis showed that the area under curve (AUC) of multivariable joint diagnosis (waist circumference, micrognathia combined with SBQ) was significantly better than the AUC of Epworth Sleepiness Scale (ESS) and SBQ (p < 0.0001 and p = 0.0002, respectively), and the results showed that AUC was 0.728. Under the optimal truncation value, the sensitivity was 73%, and the specificity was 61%, which was higher than the single index. Finally, we also constructed a nomogram model based on multiple logistic regression, to easily determine the probability of OSA in ACS patients.
CONCLUSIONS
The new screening tool has greater power than single questionnaire or measurements in screening of OSA among ACS patients.
TRIAL REGISTRATION
Clinicaltrials.gov identifier NCT03362385, registered December 5, 2017.
Topics: Humans; Acute Coronary Syndrome; Mass Screening; Micrognathism; Nurse's Role; Polysomnography; Prospective Studies; Risk Factors; Sleep Apnea, Obstructive; Surveys and Questionnaires
PubMed: 36329414
DOI: 10.1186/s12890-022-02200-x -
Genetics in Medicine : Official Journal... Jan 2023Craniofacial microsomia (CFM) represents a spectrum of craniofacial malformations, ranging from isolated microtia with or without aural atresia to underdevelopment of...
PURPOSE
Craniofacial microsomia (CFM) represents a spectrum of craniofacial malformations, ranging from isolated microtia with or without aural atresia to underdevelopment of the mandible, maxilla, orbit, facial soft tissue, and/or facial nerve. The genetic causes of CFM remain largely unknown.
METHODS
We performed genome sequencing and linkage analysis in patients and families with microtia and CFM of unknown genetic etiology. The functional consequences of damaging missense variants were evaluated through expression of wild-type and mutant proteins in vitro.
RESULTS
We studied a 5-generation kindred with microtia, identifying a missense variant in FOXI3 (p.Arg236Trp) as the cause of disease (logarithm of the odds = 3.33). We subsequently identified 6 individuals from 3 additional kindreds with microtia-CFM spectrum phenotypes harboring damaging variants in FOXI3, a regulator of ectodermal and neural crest development. Missense variants in the nuclear localization sequence were identified in cases with isolated microtia with aural atresia and found to affect subcellular localization of FOXI3. Loss of function variants were found in patients with microtia and mandibular hypoplasia (CFM), suggesting dosage sensitivity of FOXI3.
CONCLUSION
Damaging variants in FOXI3 are the second most frequent genetic cause of CFM, causing 1% of all cases, including 13% of familial cases in our cohort.
Topics: Humans; Goldenhar Syndrome; Congenital Microtia; Ear; Face; Micrognathism
PubMed: 36260083
DOI: 10.1016/j.gim.2022.09.005 -
International Journal of Oral Science Oct 2022Micrognathia is a severe craniofacial deformity affecting appearance and survival. Previous studies revealed that multiple factors involved in the osteogenesis of...
Micrognathia is a severe craniofacial deformity affecting appearance and survival. Previous studies revealed that multiple factors involved in the osteogenesis of mandibular bone have contributed to micrognathia, but concerned little on factors other than osteogenesis. In the current study, we found that ectopic activation of Fgf8 by Osr2-cre in the presumptive mesenchyme for masseter tendon in mice led to micrognathia, masseter regression, and the disrupted patterning and differentiation of masseter tendon. Since Myf5-cre;Rosa26R-Fgf8 mice exhibited the normal masseter and mandibular bone, the possibility that the micrognathia and masseter regression resulted directly from the over-expressed Fgf8 was excluded. Further investigation disclosed that a series of chondrogenic markers were ectopically activated in the developing Osr2-cre;Rosa26R-Fgf8 masseter tendon, while the mechanical sensing in the masseter and mandibular bone was obviously reduced. Thus, it suggested that the micrognathia in Osr2-cre;Rosa26R-Fgf8 mice resulted secondarily from the reduced mechanical force transmitted to mandibular bone. Consistently, when tenogenic or myogenic components were deleted from the developing mandibles, both the micrognathia and masseter degeneration took place with the decreased mechanical sensing in mandibular bone, which verified that the loss of mechanical force transmitted by masseter tendon could result in micrognathia. Furthermore, it appeared that the micrognathia resulting from the disrupted tenogenesis was attributed to the impaired osteogenic specification, instead of the differentiation in the periosteal progenitors. Our findings disclose a novel mechanism for mandibular morphogenesis, and shed light on the prevention and treatment for micrognathia.
Topics: Mice; Animals; Micrognathism; Masseter Muscle; Mandible; Osteogenesis
PubMed: 36257937
DOI: 10.1038/s41368-022-00196-y -
Pediatrics and Neonatology Jan 2023
Topics: Humans; Abnormalities, Multiple; Intellectual Disability; Micrognathism; Neck; Cardiomyopathy, Hypertrophic; High-Throughput Nucleotide Sequencing
PubMed: 36184530
DOI: 10.1016/j.pedneo.2022.07.010 -
Frontiers in Immunology 2022The COVID-19 pandemic, caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), has created an urgent global situation. Therefore, it is necessary to...
Differential gene expression profiling reveals potential biomarkers and pharmacological compounds against SARS-CoV-2: Insights from machine learning and bioinformatics approaches.
The COVID-19 pandemic, caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), has created an urgent global situation. Therefore, it is necessary to identify the differentially expressed genes (DEGs) in COVID-19 patients to understand disease pathogenesis and the genetic factor(s) responsible for inter-individual variability and disease comorbidities. The pandemic continues to spread worldwide, despite intense efforts to develop multiple vaccines and therapeutic options against COVID-19. However, the precise role of SARS-CoV-2 in the pathophysiology of the nasopharyngeal tract (NT) is still unfathomable. This study utilized machine learning approaches to analyze 22 RNA-seq data from COVID-19 patients (n = 8), recovered individuals (n = 7), and healthy individuals (n = 7) to find disease-related differentially expressed genes (DEGs). We compared dysregulated DEGs to detect critical pathways and gene ontology (GO) connected to COVID-19 comorbidities. We found 1960 and 153 DEG signatures in COVID-19 patients and recovered individuals compared to healthy controls. In COVID-19 patients, the DEG-miRNA, and DEG-transcription factors (TFs) interactions network analysis revealed that E2F1, MAX, EGR1, YY1, and SRF were the highly expressed TFs, whereas hsa-miR-19b, hsa-miR-495, hsa-miR-340, hsa-miR-101, and hsa-miR-19a were the overexpressed miRNAs. Three chemical agents (Valproic Acid, Alfatoxin B1, and Cyclosporine) were abundant in COVID-19 patients and recovered individuals. Mental retardation, mental deficit, intellectual disability, muscle hypotonia, micrognathism, and cleft palate were the significant diseases associated with COVID-19 by sharing DEGs. Finally, the detected DEGs mediated by TFs and miRNA expression indicated that SARS-CoV-2 infection might contribute to various comorbidities. Our results provide the common DEGs between COVID-19 patients and recovered humans, which suggests some crucial insights into the complex interplay between COVID-19 progression and the recovery stage, and offer some suggestions on therapeutic target identification in COVID-19 caused by the SARS-CoV-2.
Topics: Biomarkers; COVID-19; Computational Biology; Gene Expression Profiling; Humans; Machine Learning; MicroRNAs; Pandemics; SARS-CoV-2; COVID-19 Drug Treatment
PubMed: 36059456
DOI: 10.3389/fimmu.2022.918692 -
International Journal of Molecular... Aug 2022Meier−Gorlin syndrome (MGS) is a rare genetic developmental disorder that causes primordial proportional dwarfism, microtia, the absence of or hypoplastic patellae and...
Meier−Gorlin syndrome (MGS) is a rare genetic developmental disorder that causes primordial proportional dwarfism, microtia, the absence of or hypoplastic patellae and other skeletal anomalies. Skeletal symptoms overlapping with other syndromes make MGS difficult to diagnose clinically. We describe a 3-year-old boy with short stature, recurrent respiratory infections, short-rib dysplasia, tower head and facial dysmorphisms who was admitted to the Tomsk Genetic Clinic to verify a clinical diagnosis of Jeune syndrome. Clinical exome sequencing revealed two variants (compound heterozygosity) in the ORC6 gene: c.2T>C(p.Met1Thr) and c.449+5G>A. In silico analysis showed the pathogenicity of these two mutations and predicted a decrease in donor splicing site strength for c.449+5G>A. An in vitro minigene assay indicated that variant c.449+5G>A causes complete skipping of exon 4 in the ORC6 gene. The parents requested urgent prenatal testing for MGS for the next pregnancy, but it ended in a miscarriage. Our results may help prevent MGS misdiagnosis in the future. We also performed in silico and functional analyses of ORC6 mutations and developed a restriction fragment length polymorphism and haplotype-based short-tandem-repeat assay for prenatal genetic testing for MGS. These findings should elucidate MGS etiology and improve the quality of genetic counselling for affected families.
Topics: Child, Preschool; Congenital Microtia; Diagnostic Errors; Dwarfism; Genetic Testing; Growth Disorders; Humans; Male; Micrognathism; Mutation; Origin Recognition Complex; Patella
PubMed: 36012502
DOI: 10.3390/ijms23169234 -
BMC Pediatrics Aug 2022Coffin-Siris syndrome (CSS) is a rare autosomal dominant disorder characterized by intellectual disability, developmental delay, and characteristic facial features. Few...
BACKGROUND
Coffin-Siris syndrome (CSS) is a rare autosomal dominant disorder characterized by intellectual disability, developmental delay, and characteristic facial features. Few patients with cutaneous phenotype in this rare syndrome have been reported.
CASE PRESENTATION
Herein, we describe a 12-year-old Chinese girl diagnosed with CSS, who was referred to our hospital because of intellectual disability and short stature. Prominent characteristics of the cutaneous system were observed: (1) A congenital giant nevus from the left frontal and temporal regions to the entire left scalp; and (2) multiple melanocytic nevi on the face and trunk. Whole exome sequencing revealed a novel heterozygous variant in the ARID1B gene. Recombinant human growth hormone (rhGH) was given for short stature, and resulted in significantly improved height. No enlargement or malignant transformation of nevi occurred within 4 years of follow-up.
CONCLUSION
The symptoms in cutaneous system is noteworthy,which may be a neglected phenotype in CSS.The therapeutic response of growth hormone is effective in this patient and no tumor related signs were found.
Topics: Abnormalities, Multiple; Child; DNA-Binding Proteins; Dwarfism; Face; Female; Hand Deformities, Congenital; Humans; Intellectual Disability; Micrognathism; Neck; Nevus, Pigmented; Transcription Factors
PubMed: 35964110
DOI: 10.1186/s12887-022-03535-4 -
Disease Models & Mechanisms Aug 2022Ciliopathies represent a disease class characterized by a broad range of phenotypes including polycystic kidneys and skeletal anomalies. Ciliopathic skeletal phenotypes...
Ciliopathies represent a disease class characterized by a broad range of phenotypes including polycystic kidneys and skeletal anomalies. Ciliopathic skeletal phenotypes are among the most common and most difficult to treat due to a poor understanding of the pathological mechanisms leading to disease. Using an avian model (talpid2) for a human ciliopathy with both kidney and skeletal anomalies (orofaciodigital syndrome 14), we identified disruptions in the FGF23-PTH axis that resulted in reduced calcium uptake in the developing mandible and subsequent micrognathia. Although pharmacological intervention with the U.S. Food and Drug Administration (FDA)-approved pan-FGFR inhibitor AZD4547 alone rescued expression of the FGF target SPRY2, it did not significantly rescue micrognathia. In contrast, treatment with a cocktail of AZD4547 and teriparatide acetate, a PTH agonist and FDA-approved treatment for osteoporosis, resulted in molecular, cellular and phenotypic rescue of ciliopathic micrognathia in talpid2 mutants. Together, these data provide novel insight into pathological molecular mechanisms associated with ciliopathic skeletal phenotypes and a potential therapeutic strategy for a pleiotropic disease class with limited to no treatment options.
Topics: Cilia; Ciliopathies; Humans; Intracellular Signaling Peptides and Proteins; Membrane Proteins; Micrognathism; Phenotype; Proteins
PubMed: 35818799
DOI: 10.1242/dmm.049611 -
American Journal of Medical Genetics.... Sep 2022Coffin-Siris syndrome (CSS) is an autosomal dominant neurodevelopmental syndrome that can present with a variety of structural birth defects. Pathogenic variants in 12... (Review)
Review
Coffin-Siris syndrome (CSS) is an autosomal dominant neurodevelopmental syndrome that can present with a variety of structural birth defects. Pathogenic variants in 12 genes have been shown to cause CSS. Most of these genes encode proteins that are a part of the mammalian switch/sucrose non-fermentable (mSWI/SNF; BAF) complex. An association between genes that cause CSS and congenital diaphragmatic hernia (CDH) has been suggested based on case reports and the analysis of CSS and CDH cohorts. Here, we describe an unpublished individual with CSS and CDH, and we report additional clinical information on four published cases. Data from these individuals, and a review of the literature, provide evidence that deleterious variants in ARID1B, ARID1A, SMARCB1, SMARCA4, SMARCE1, ARID2, DPF2, and SMARCC2, which are associated with CSS types 1-8, respectively, are associated with the development of CDH. This suggests that additional genetic testing to identify a separate cause of CDH in an individual with CSS may be unwarranted, and that comprehensive genetic testing for individuals with non-isolated CDH should include an evaluation of CSS-related genes. These data also suggest that the mSWI/SNF (BAF) complex may play an important role in diaphragm development.
Topics: Abnormalities, Multiple; Chromosomal Proteins, Non-Histone; DNA Helicases; DNA-Binding Proteins; Face; Hand Deformities, Congenital; Hernias, Diaphragmatic, Congenital; Humans; Intellectual Disability; Micrognathism; Neck; Nuclear Proteins; Transcription Factors
PubMed: 35796094
DOI: 10.1002/ajmg.a.62889 -
JCI Insight May 2022The eukaryotic CDC45/MCM2-7/GINS (CMG) helicase unwinds the DNA double helix during DNA replication. The GINS subcomplex is required for helicase activity and is,...
The eukaryotic CDC45/MCM2-7/GINS (CMG) helicase unwinds the DNA double helix during DNA replication. The GINS subcomplex is required for helicase activity and is, therefore, essential for DNA replication and cell viability. Here, we report the identification of 7 individuals from 5 unrelated families presenting with a Meier-Gorlin syndrome-like (MGS-like) phenotype associated with hypomorphic variants of GINS3, a gene not previously associated with this syndrome. We found that MGS-associated GINS3 variants affecting aspartic acid 24 (D24) compromised cell proliferation and caused accumulation of cells in S phase. These variants shortened the protein half-life, altered key protein interactions at the replisome, and negatively influenced DNA replication fork progression. Yeast expressing MGS-associated variants of PSF3 (the yeast GINS3 ortholog) also displayed impaired growth, S phase progression defects, and decreased Psf3 protein stability. We further showed that mouse embryos homozygous for a D24 variant presented intrauterine growth retardation and did not survive to birth, and that fibroblasts derived from these embryos displayed accelerated cellular senescence. Taken together, our findings implicate GINS3 in the pathogenesis of MGS and support the notion that hypomorphic variants identified in this gene impaired cell and organismal growth by compromising DNA replication.
Topics: Animals; Chromosomal Proteins, Non-Histone; Congenital Microtia; DNA Replication; Growth Disorders; Humans; Mice; Micrognathism; Minichromosome Maintenance Proteins; Patella; Saccharomyces cerevisiae
PubMed: 35603789
DOI: 10.1172/jci.insight.155648