Upstream Open Reading Frames Cause Widespread Reduction of Protein Expression and Are Polymorphic Among Humans
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Novel Heterozygous Pathogenic Variants in CHUK in a Patient With
Cadieux-Dion et al. BMC Medical Genetics (2018) 19:41 https://doi.org/10.1186/s12881-018-0556-2 CASE REPORT Open Access Novel heterozygous pathogenic variants in CHUK in a patient with AEC-like phenotype, immune deficiencies and 1q21.1 microdeletion syndrome: a case report Maxime Cadieux-Dion1* , Nicole P. Safina2,6,7, Kendra Engleman2, Carol Saunders1,3,7, Elena Repnikova1,2, Nikita Raje4, Kristi Canty5, Emily Farrow1,6, Neil Miller1, Lee Zellmer3 and Isabelle Thiffault1,2,3 Abstract Background: Ectodermal dysplasias (ED) are a group of diseases that affects the development or function of the teeth, hair, nails and exocrine and sebaceous glands. One type of ED, ankyloblepharon-ectodermal defects-cleft lip/ palate syndrome (AEC or Hay-Wells syndrome), is an autosomal dominant disease characterized by the presence of skin erosions affecting the palms, soles and scalp. Other clinical manifestations include ankyloblepharon filiforme adnatum, cleft lip, cleft palate, craniofacial abnormalities and ectodermal defects such as sparse wiry hair, nail changes, dental changes, and subjective hypohydrosis. Case presentation: We describe a patient presenting clinical features reminiscent of AEC syndrome in addition to recurrent infections suggestive of immune deficiency. Genetic testing for TP63, IRF6 and RIPK4 was negative. Microarray analysis revealed a 2 MB deletion on chromosome 1 (1q21.1q21.2). Clinical exome sequencing uncovered compound heterozygous variants in CHUK; a maternally-inherited frameshift variant (c.1365del, p.Arg457Aspfs*6) and a de novo missense variant (c.1388C > A, p.Thr463Lys) on the paternal allele. Conclusions: To our knowledge, this is the fourth family reported with CHUK-deficiency and the second patient with immune abnormalities. -
Screening for Obstructive Sleep Apnea in Children with Syndromic Cleft Lip And/Or Palate* Jason Silvestre, Youssef Tahiri, J
Journal of Plastic, Reconstructive & Aesthetic Surgery (2014) 67, 1475e1480 Screening for obstructive sleep apnea in children with syndromic cleft lip and/or palate* Jason Silvestre, Youssef Tahiri, J. Thomas Paliga, Jesse A. Taylor* Division of Plastic Surgery, The Perelman School of Medicine at the University of Pennsylvania, The Children’s Hospital of Philadelphia, USA Received 20 December 2013; accepted 22 July 2014 KEYWORDS Summary Background: Craniofacial malformations including cleft lip and/or palate (CL/P) Obstructive sleep increase risk for obstructive sleep apnea (OSA). While 30% of CL/P occurs in the context of un- apnea; derlying genetic syndromes, few studies have investigated the prevalence of OSA in this high- Pediatric; risk group. This study aims to determine the incidence and risk factors of positive screening for Questionnaire; OSA in this complex patient population. Screening; Methods: The Pediatric Sleep Questionnaire (PSQ) was prospectively administered to all pa- Cleft lip and palate tients cared for by the cleft lip and palate clinic at the Children’s Hospital of Philadelphia be- tween January 2011 and August 2013. The PSQ is a 22-item, validated screening tool for OSA with a sensitivity and specificity of 0.83 and 0.87 in detecting an apnea-hypopnea index (AHI) >5/hour in healthy children. The Fisher exact and Chi-square tests were used for pur- poses of comparison. Results: 178 patients with syndromic CL/P completed the PSQ. Mean cohort age was 8.1 Æ 4.4 years. Patients were predominately female (53.9%), Caucasian (78.1%), and had Veau Class II cleft (50.6%). -
Supplementary Materials
Supplementary materials Supplementary Table S1: MGNC compound library Ingredien Molecule Caco- Mol ID MW AlogP OB (%) BBB DL FASA- HL t Name Name 2 shengdi MOL012254 campesterol 400.8 7.63 37.58 1.34 0.98 0.7 0.21 20.2 shengdi MOL000519 coniferin 314.4 3.16 31.11 0.42 -0.2 0.3 0.27 74.6 beta- shengdi MOL000359 414.8 8.08 36.91 1.32 0.99 0.8 0.23 20.2 sitosterol pachymic shengdi MOL000289 528.9 6.54 33.63 0.1 -0.6 0.8 0 9.27 acid Poricoic acid shengdi MOL000291 484.7 5.64 30.52 -0.08 -0.9 0.8 0 8.67 B Chrysanthem shengdi MOL004492 585 8.24 38.72 0.51 -1 0.6 0.3 17.5 axanthin 20- shengdi MOL011455 Hexadecano 418.6 1.91 32.7 -0.24 -0.4 0.7 0.29 104 ylingenol huanglian MOL001454 berberine 336.4 3.45 36.86 1.24 0.57 0.8 0.19 6.57 huanglian MOL013352 Obacunone 454.6 2.68 43.29 0.01 -0.4 0.8 0.31 -13 huanglian MOL002894 berberrubine 322.4 3.2 35.74 1.07 0.17 0.7 0.24 6.46 huanglian MOL002897 epiberberine 336.4 3.45 43.09 1.17 0.4 0.8 0.19 6.1 huanglian MOL002903 (R)-Canadine 339.4 3.4 55.37 1.04 0.57 0.8 0.2 6.41 huanglian MOL002904 Berlambine 351.4 2.49 36.68 0.97 0.17 0.8 0.28 7.33 Corchorosid huanglian MOL002907 404.6 1.34 105 -0.91 -1.3 0.8 0.29 6.68 e A_qt Magnogrand huanglian MOL000622 266.4 1.18 63.71 0.02 -0.2 0.2 0.3 3.17 iolide huanglian MOL000762 Palmidin A 510.5 4.52 35.36 -0.38 -1.5 0.7 0.39 33.2 huanglian MOL000785 palmatine 352.4 3.65 64.6 1.33 0.37 0.7 0.13 2.25 huanglian MOL000098 quercetin 302.3 1.5 46.43 0.05 -0.8 0.3 0.38 14.4 huanglian MOL001458 coptisine 320.3 3.25 30.67 1.21 0.32 0.9 0.26 9.33 huanglian MOL002668 Worenine -
Bartsocas-Papas Syndrome: a Lethal Multiple Pterygium Syndrome Neonatology Section
DOI: 10.7860/JCDR/2021/45819.14401 Case Report Bartsocas-Papas Syndrome: A Lethal Multiple Pterygium Syndrome Neonatology Section SUMITA MEHTA1, EKTA KALE2, TARUN KUMAR RAVI3, ANKITA MANN4, PRATIBHA NANDA5 ABSTRACT Bartsocas-Papas Syndrome (BPS) is a very rare autosomal recessive syndrome characterised by marked craniofacial deformities, multiple pterygia of various joints, limb and genital abnormalities. It is mostly associated with mutation in the gene encoding Receptor Interacting Serine/Threonine Kinase 4 (RIPK4) required for keratinocyte differentiation. The syndrome is generally lethal and majority of babies die in-utero or in the early neonatal period. This is a report about a neonate born with characteristic clinical features of BPS including severe craniofacial and ophthalmic abnormalities, limb deformities and multiple pterygia at popliteal, axillary and inguinal region. The baby had respiratory distress at birth and was managed conservatively on Continuous Positive Airway Pressure (CPAP)/Oxygen hood and injectable antibiotics for two weeks and then referred for further work-up to a tertiary hospital. The parents took the baby home against the advice of the treating doctors and she subsequently died after 10 days. BPS is associated with high mortality and so all efforts should be directed towards diagnosing it early antenatally when termination of pregnancy is a viable option. This is possible by having a high index of suspicion in couples with consanguineous marriages or with a positive family history. Keywords: Craniofacial abnormalities, Genitals, Joints, Limb, Mutation, Popliteal pterygium syndrome CASE REPORT A 27-year-old primigravida, with previous two antenatal visits, had a breech vaginal delivery at 37 weeks of gestation. -
Appendix 2. Significantly Differentially Regulated Genes in Term Compared with Second Trimester Amniotic Fluid Supernatant
Appendix 2. Significantly Differentially Regulated Genes in Term Compared With Second Trimester Amniotic Fluid Supernatant Fold Change in term vs second trimester Amniotic Affymetrix Duplicate Fluid Probe ID probes Symbol Entrez Gene Name 1019.9 217059_at D MUC7 mucin 7, secreted 424.5 211735_x_at D SFTPC surfactant protein C 416.2 206835_at STATH statherin 363.4 214387_x_at D SFTPC surfactant protein C 295.5 205982_x_at D SFTPC surfactant protein C 288.7 1553454_at RPTN repetin solute carrier family 34 (sodium 251.3 204124_at SLC34A2 phosphate), member 2 238.9 206786_at HTN3 histatin 3 161.5 220191_at GKN1 gastrokine 1 152.7 223678_s_at D SFTPA2 surfactant protein A2 130.9 207430_s_at D MSMB microseminoprotein, beta- 99.0 214199_at SFTPD surfactant protein D major histocompatibility complex, class II, 96.5 210982_s_at D HLA-DRA DR alpha 96.5 221133_s_at D CLDN18 claudin 18 94.4 238222_at GKN2 gastrokine 2 93.7 1557961_s_at D LOC100127983 uncharacterized LOC100127983 93.1 229584_at LRRK2 leucine-rich repeat kinase 2 HOXD cluster antisense RNA 1 (non- 88.6 242042_s_at D HOXD-AS1 protein coding) 86.0 205569_at LAMP3 lysosomal-associated membrane protein 3 85.4 232698_at BPIFB2 BPI fold containing family B, member 2 84.4 205979_at SCGB2A1 secretoglobin, family 2A, member 1 84.3 230469_at RTKN2 rhotekin 2 82.2 204130_at HSD11B2 hydroxysteroid (11-beta) dehydrogenase 2 81.9 222242_s_at KLK5 kallikrein-related peptidase 5 77.0 237281_at AKAP14 A kinase (PRKA) anchor protein 14 76.7 1553602_at MUCL1 mucin-like 1 76.3 216359_at D MUC7 mucin 7, -
Reproductive Biology and Endocrinology Biomed Central
Reproductive Biology and Endocrinology BioMed Central Research Open Access Identification, cloning and functional characterization of novel beta-defensins in the rat (Rattus norvegicus) Suresh Yenugu1,3, Vishnu Chintalgattu2, Christopher J Wingard2, Yashwanth Radhakrishnan1, Frank S French1 and Susan H Hall*1 Address: 1Laboratories for Reproductive Biology, Department of Pediatrics, University of North Carolina, Chapel Hill, North Carolina 27599, USA, 2Department of Physiology, Brody School of Medicine, East Carolina University, Greenville, North Carolina 27834, USA and 3Department of Biochemistry and Molecular Biology, Pondicherry University, Pondicherry, 605014, India Email: Suresh Yenugu - [email protected]; Vishnu Chintalgattu - [email protected]; Christopher J Wingard - [email protected]; Yashwanth Radhakrishnan - [email protected]; Frank S French - [email protected]; Susan H Hall* - [email protected] * Corresponding author Published: 04 February 2006 Received: 23 November 2005 Accepted: 04 February 2006 Reproductive Biology and Endocrinology2006, 4:7 doi:10.1186/1477-7827-4-7 This article is available from: http://www.rbej.com/content/4/1/7 © 2006Yenugu et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Abstract Background: beta-defensins are small cationic peptides that exhibit broad spectrum antimicrobial properties. The majority of beta-defensins identified in humans are predominantly expressed in the male reproductive tract and have roles in non-immunological processes such as sperm maturation and capacitation. Characterization of novel defensins in the male reproductive tract can lead to increased understanding of their dual roles in immunity and sperm maturation. -
2019 Literature Review
2019 ANNUAL SEMINAR CHARLESTON, SC Special Care Advocates in Dentistry 2019 Lit. Review (SAID’s Search of Dental Literature Published in Calendar Year 2018*) Compiled by: Dr. Mannie Levi Dr. Douglas Veazey Special Acknowledgement to Janina Kaldan, MLS, AHIP of the Morristown Medical Center library for computer support and literature searches. Recent journal articles related to oral health care for people with mental and physical disabilities. Search Program = PubMed Database = Medline Journal Subset = Dental Publication Timeframe = Calendar Year 2016* Language = English SAID Search-Term Results = 1539 Initial Selection Result = 503 articles Final Selection Result =132 articles SAID Search-Terms Employed: 1. Intellectual disability 21. Protective devices 2. Mental retardation 22. Moderate sedation 3. Mental deficiency 23. Conscious sedation 4. Mental disorders 24. Analgesia 5. Mental health 25. Anesthesia 6. Mental illness 26. Dental anxiety 7. Dental care for disabled 27. Nitrous oxide 8. Dental care for chronically ill 28. Gingival hyperplasia 9. Special Needs Dentistry 29. Gingival hypertrophy 10. Disabled 30. Autism 11. Behavior management 31. Silver Diamine Fluoride 12. Behavior modification 32. Bruxism 13. Behavior therapy 33. Deglutition disorders 14. Cognitive therapy 34. Community dentistry 15. Down syndrome 35. Access to Dental Care 16. Cerebral palsy 36. Gagging 17. Epilepsy 37. Substance abuse 18. Enteral nutrition 38. Syndromes 19. Physical restraint 39. Tooth brushing 20. Immobilization 40. Pharmaceutical preparations Program: EndNote X3 used to organize search and provide abstract. Copyright 2009 Thomson Reuters, Version X3 for Windows. *NOTE: The American Dental Association is responsible for entering journal articles into the National Library of Medicine database; however, some articles are not entered in a timely manner. -
Whole Genome Sequencing of Familial Non-Medullary Thyroid Cancer Identifies Germline Alterations in MAPK/ERK and PI3K/AKT Signaling Pathways
biomolecules Article Whole Genome Sequencing of Familial Non-Medullary Thyroid Cancer Identifies Germline Alterations in MAPK/ERK and PI3K/AKT Signaling Pathways Aayushi Srivastava 1,2,3,4 , Abhishek Kumar 1,5,6 , Sara Giangiobbe 1, Elena Bonora 7, Kari Hemminki 1, Asta Försti 1,2,3 and Obul Reddy Bandapalli 1,2,3,* 1 Division of Molecular Genetic Epidemiology, German Cancer Research Center (DKFZ), D-69120 Heidelberg, Germany; [email protected] (A.S.); [email protected] (A.K.); [email protected] (S.G.); [email protected] (K.H.); [email protected] (A.F.) 2 Hopp Children’s Cancer Center (KiTZ), D-69120 Heidelberg, Germany 3 Division of Pediatric Neurooncology, German Cancer Research Center (DKFZ), German Cancer Consortium (DKTK), D-69120 Heidelberg, Germany 4 Medical Faculty, Heidelberg University, D-69120 Heidelberg, Germany 5 Institute of Bioinformatics, International Technology Park, Bangalore 560066, India 6 Manipal Academy of Higher Education (MAHE), Manipal, Karnataka 576104, India 7 S.Orsola-Malphigi Hospital, Unit of Medical Genetics, 40138 Bologna, Italy; [email protected] * Correspondence: [email protected]; Tel.: +49-6221-42-1709 Received: 29 August 2019; Accepted: 10 October 2019; Published: 13 October 2019 Abstract: Evidence of familial inheritance in non-medullary thyroid cancer (NMTC) has accumulated over the last few decades. However, known variants account for a very small percentage of the genetic burden. Here, we focused on the identification of common pathways and networks enriched in NMTC families to better understand its pathogenesis with the final aim of identifying one novel high/moderate-penetrance germline predisposition variant segregating with the disease in each studied family. -
Van Der Woude Syndrome
Journal of Dental Health Oral Disorders & Therapy Mini Review Open Access Van Der Woude syndrome Introduction Volume 7 Issue 2 - 2017 The Van der Woude syndrome is an autosomal dominant syndrome Ambarkova Vesna and was originally described by Van der Woude in 1954, as a dominant Department of Paediatric and Preventive Dentistry, University inheritance pattern with variable penetrance and expression, even St. Cyril and Methodius, Macedonia within families. Even monozygotic twins may be affected to markedly different degrees.1 Correspondence: Vesna Ambarkova, Department of Paediatric and Preventive Dentistry, Faculty of Dental Medicine, University Etiology St. Cyril and Methodius, Mother Theresa 17 University Dental Clinic Center Sv. Pantelejmon Skopje 1000, Macedonia, Tel The syndrome has been linked to a deletion in chromosome 38970686333, Email 1q32-q41, but a second chromosomal locus at 1p34 has also been Received: April 12, 2017 | Published: May 02, 2017 identified. The exact mechanism of the interferon regulatory factor 6 (IRF6) gene mutations on craniofacial development is uncertain. Chromosomal mutations that cause van der Woude syndrome and are associated with IRF-6 gene mutations. A potential modifying gene has been identified at 17p11.2-p11.1. Los et al stated that most cases of Van der Woude syndrome are caused by a mutation to interferon regulatory factor 6 on chromosome I.2 They describe a unique case mother presented with a classic Van der Woude Syndrome, while the of the two syndromes occurring concurrently though apparently maternal grandfather had Van der Woude Syndrome as well as minor independently in a girl with Van der Woude syndrome and pituitary signs of popliteal pterygium syndrome. -
Identification of Novel Genes in Human Airway Epithelial Cells Associated with Chronic Obstructive Pulmonary Disease (COPD) Usin
www.nature.com/scientificreports OPEN Identifcation of Novel Genes in Human Airway Epithelial Cells associated with Chronic Obstructive Received: 6 July 2018 Accepted: 7 October 2018 Pulmonary Disease (COPD) using Published: xx xx xxxx Machine-Based Learning Algorithms Shayan Mostafaei1, Anoshirvan Kazemnejad1, Sadegh Azimzadeh Jamalkandi2, Soroush Amirhashchi 3, Seamas C. Donnelly4,5, Michelle E. Armstrong4 & Mohammad Doroudian4 The aim of this project was to identify candidate novel therapeutic targets to facilitate the treatment of COPD using machine-based learning (ML) algorithms and penalized regression models. In this study, 59 healthy smokers, 53 healthy non-smokers and 21 COPD smokers (9 GOLD stage I and 12 GOLD stage II) were included (n = 133). 20,097 probes were generated from a small airway epithelium (SAE) microarray dataset obtained from these subjects previously. Subsequently, the association between gene expression levels and smoking and COPD, respectively, was assessed using: AdaBoost Classifcation Trees, Decision Tree, Gradient Boosting Machines, Naive Bayes, Neural Network, Random Forest, Support Vector Machine and adaptive LASSO, Elastic-Net, and Ridge logistic regression analyses. Using this methodology, we identifed 44 candidate genes, 27 of these genes had been previously been reported as important factors in the pathogenesis of COPD or regulation of lung function. Here, we also identifed 17 genes, which have not been previously identifed to be associated with the pathogenesis of COPD or the regulation of lung function. The most signifcantly regulated of these genes included: PRKAR2B, GAD1, LINC00930 and SLITRK6. These novel genes may provide the basis for the future development of novel therapeutics in COPD and its associated morbidities. -
Characterization and Antimicrobial Efficacy of Bovine Dermcidin-Like Antimicrobial Peptide Gene
International Journal of Pharmaceutical and Phytopharmacological Research (eIJPPR) | June 2020 | Volume 10 | Issue 3| Page 108-117 Nevien M. Sabry, Characterization and Antimicrobial Efficacy of Bovine Dermcidin-Like Antimicrobial Peptide Gene Characterization and Antimicrobial Efficacy of Bovine Dermcidin-Like Antimicrobial Peptide Gene Nevien M. Sabry 1, Tarek A. A. Moussa 2* 1 Cell Biology Department, Genetic Engineering and Biotechnology Division, National Research Centre, Giza 12622, Egypt. 2 Botany and Microbiology Department, Faculty of Science, Cairo University, Giza 12613, Egypt. ABSTRACT Due to the significance of the antimicrobial peptides as innate immune effectors, in this study, a novel bovine antimicrobial peptide and its antimicrobial spectrum were described. RNA isolation from various tissues and RT-PCR were conducted. The DCD-like peptide was synthesized, and its antimicrobial effect was analyzed. The bovine dermcidin-like gene contains 5 exons intermittent by 4 introns. Bovine DCD-like mRNA was 398 bp with ORF size of 336 bp. Bovine DCD- like was expressed in skin and blood. Analysis of amino acid compositions showed that cysteine was repeated six times, which indicates the presence of 3 disulfide bonds that play a role in the peptide stability. Bovine DCD-like had an antimicrobial effect on Enterococcus faecalis, Streptococcus bovis, and Staphylococcus epidermidis, which was highest at 50 and 100 µg/ml. The effect on Candida albicans and Escherichia coli was slightly low. In Staphylococcus aureus, the activity of bovine DCD-like was affected greatly at pH 4.5 and 5.5. The optimum salt concentrations were 50 and 100 mM with E. coli and all other bacterial strains, respectively. -
Chromosomal Microarray Analysis in Turkish Patients with Unexplained Developmental Delay and Intellectual Developmental Disorders
177 Arch Neuropsychitry 2020;57:177−191 RESEARCH ARTICLE https://doi.org/10.29399/npa.24890 Chromosomal Microarray Analysis in Turkish Patients with Unexplained Developmental Delay and Intellectual Developmental Disorders Hakan GÜRKAN1 , Emine İkbal ATLI1 , Engin ATLI1 , Leyla BOZATLI2 , Mengühan ARAZ ALTAY2 , Sinem YALÇINTEPE1 , Yasemin ÖZEN1 , Damla EKER1 , Çisem AKURUT1 , Selma DEMİR1 , Işık GÖRKER2 1Faculty of Medicine, Department of Medical Genetics, Edirne, Trakya University, Edirne, Turkey 2Faculty of Medicine, Department of Child and Adolescent Psychiatry, Trakya University, Edirne, Turkey ABSTRACT Introduction: Aneuploids, copy number variations (CNVs), and single in 39 (39/123=31.7%) patients. Twelve CNV variant of unknown nucleotide variants in specific genes are the main genetic causes of significance (VUS) (9.75%) patients and 7 CNV benign (5.69%) patients developmental delay (DD) and intellectual disability disorder (IDD). were reported. In 6 patients, one or more pathogenic CNVs were These genetic changes can be detected using chromosome analysis, determined. Therefore, the diagnostic efficiency of CMA was found to chromosomal microarray (CMA), and next-generation DNA sequencing be 31.7% (39/123). techniques. Therefore; In this study, we aimed to investigate the Conclusion: Today, genetic analysis is still not part of the routine in the importance of CMA in determining the genomic etiology of unexplained evaluation of IDD patients who present to psychiatry clinics. A genetic DD and IDD in 123 patients. diagnosis from CMA can eliminate genetic question marks and thus Method: For 123 patients, chromosome analysis, DNA fragment analysis alter the clinical management of patients. Approximately one-third and microarray were performed. Conventional G-band karyotype of the positive CMA findings are clinically intervenable.