DOCSLIB.ORG

Blueprint Genetics Congenital Structural Heart Disease Panel

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text

Load more

Congenital Structural Heart Disease Panel Test code: CA1501 Is a 114 gene panel that includes assessment of non-coding variants. Is ideal for patients with congenital heart disease, particularly those with features of hereditary disorders. Is not ideal for patients suspected to have a ciliopathy or a rasopathy. For those patients, please consider our Primary Ciliary Dyskinesia Panel and our Noonan Syndrome Panel, respectively. About Congenital Structural Heart Disease There are many types of congenital heart disease (CHD) ranging from simple asymptomatic defects to complex defects with severe, life-threatening symptoms. CHDs are the most common type of birth defect and affect at least 8 out of every 1,000 newborns. Annually, more than 35,000 babies in the United States are born with CHDs. Many of these CHDs are simple conditions and need no treatment or are easily repaired. Some babies are born with complex CHD requiring special medical care. The diagnosis and treatment of complex CHDs has greatly improved over the past few decades. As a result, almost all children who have complex heart defects survive to adulthood and can live active, productive lives. However, many patients who have complex CHDs continue to need special heart care throughout their lives. In the United States, more than 1 million adults are living with congenital heart disease. Availability 4 weeks Gene Set Description Genes in the Congenital Structural Heart Disease Panel and their clinical significance Gene Associated phenotypes Inheritance ClinVar HGMD ABL1 Congenital heart defects and skeletal malformations syndrome AD 30 5 (CHDSKM) ACTA2 Aortic aneurysm, familial thoracic, Moyamoya disease, Multisystemic AD 20 76 smooth muscle dysfunction syndrome ACTB* Baraitser-Winter syndrome AD 55 60 ACTC1 Left ventricular noncompaction, Hypertrophic cardiomyopathy (HCM), AD 23 63 Cardiomyopathy, restrictive, Atrial septal defect, Dilated cardiomyopathy (DCM) ACTG1* Deafness, Baraitser-Winter syndrome AD 27 47 ACVR1 Fibrodysplasia ossificans progressiva AD 14 19 ACVR2B Heterotaxy, visceral, 4, autosomal AD 1 2 ADAMTS10 Weill-Marchesani syndrome AR 8 14 ADAMTS17 Weill-Marchesani-like syndrome AR 6 7 AFF4 Cognitive impairment, coarse facies, Heart defects, Obesity, Pulmonary AD 3 3 involvement, Short stature, and skeletal dysplasia (CHOPS syndrome) https://blueprintgenetics.com/ AMMECR1 Midface hypoplasia, hearing impairment, elliptocytosis, and XL 4 5 nephrocalcinosis ARHGAP31 Adams-Oliver syndrome AD 3 6 ARID1A Coffin-Siris syndrome, Mental retardation AD 27 35 ARID1B Coffin-Siris syndrome, Mental retardation AD 153 185 B3GAT3* Multiple joint dislocations, short stature, craniofacial dysmorphism, and AR 6 13 congenital heart defects BCOR Microphthalmia, syndromic, Oculofaciocardiodental syndrome XL 40 53 BMPR2 Pulmonary hypertension, primary, Pulmonary venoocclusive disease AD 391 572 BRAF* LEOPARD syndrome, Noonan syndrome, Cardiofaciocutaneous syndrome AD 134 65 C12ORF57 Corpus callosum hypoplasia, recessive, Temtamy syndrome AR 7 6 CBL Noonan syndrome-like disorder with or without juvenile myelomonocytic AD 24 43 leukemia CDK13 Congenital heart defects, dysmorphic facial features, and intellectual AD 13 20 developmental disorder CDK9 AR 1 CFAP53 Heterotaxy, visceral, 6, autosomal recessive AR 4 4 CHD4 Sifrim-Hitz-Weiss syndrome AD 14 21 CHD7 Isolated gonadotropin-releasing hormone deficiency, CHARGE syndrome AD 276 860 CHRM2 Dilated cardiomyopathy (DCM) AD/AR 1 CREBBP Rubinstein-Taybi syndrome AD 175 362 CRELD1 Atrioventricular septal defect, partial, with or without heterotaxy AD 2 16 CTC1 Cerebroretinal microangiopathy with calcifications and cysts AR 21 33 DHCR7 Smith-Lemli-Opitz syndrome AR 88 217 DLL4 Adams-Oliver syndrome AD 13 14 DOCK6 Adams-Oliver syndrome AR 21 21 EFTUD2 Mandibulofacial dysostosis with microcephaly, Esophageal atresia, AD 45 99 syndromic EHMT1 Kleefstra syndrome AD 86 89 EIF2AK4 Pulmonary venoocclusive disease AR 27 84 ELN Cutis laxa, Supravalvular aortic stenosis AD 78 113 ENG Juvenile polyposis syndrome, Hereditary hemorrhagic telangiectasia AD 158 491 EOGT Adams-Oliver syndrome AR 8 5 https://blueprintgenetics.com/ EP300 Rubinstein-Taybi syndrome AD 63 101 EVC Weyers acrofacial dysostosis, Ellis-van Creveld syndrome AD/AR 58 83 EVC2 Ellis-van Creveld syndrome, Weyers acrodental dysostosis AD/AR 78 75 FLNA Frontometaphyseal dysplasia, Osteodysplasty Melnick-Needles, XL 133 257 Otopalatodigital syndrome type 1, Otopalatodigital syndrome type 2, Terminal osseous dysplasia with pigmentary defects FOXC1 Axenfeld-Rieger syndrome, Iridogoniodysgenesis, Peters anomaly AD 46 135 FOXF1 Alveolar capillary dysplasia with misalignment of pulmonary veins AD 10 102 FOXH1 Congenital heart malformations, Holoprosencephaly AD 33 FOXP1 Mental retardation with language impairment and autistic features, AD 48 76 Congenital heart malformations GATA4 Tetralogy of Fallot, Atrioventricular septal defect, Testicular anomalies AD 37 140 with or without congenital heart disease, Ventricular septal defect, Atrial septal defect GATA5 Familial atrial fibrillation, Tetralogy of Fallot, Single ventricular septal AD 5 32 defect GATA6 Heart defects, congenital, and other congenital anomalies, Atrial septal AD 16 82 defect 9, atrioventricular septal defect 5, Persistent truncus arteriosus, Tetralogy of Fallot GDF1 Transposition of the great arteries, dextro-looped 3, Double-outlet right AR 11 15 ventricle GJA1* Oculodentodigital dysplasia mild type, Oculodentodigital dysplasia severe AD/AR 31 107 type, Syndactyly type 3 GJA5 Progressive familial heart block, Atrial standstill, digenic, Atrial fibrillation AD/Digenic 8 34 GPC3 Simpson-Golabi-Behmel syndrome XL 33 75 HAND1 Congenital heart defects, Dilated cardiomyopathy AD 9 HAND2 Dilated cardiomyopathy (DCM), Congenital heart malformations AD 2 5 HDAC8 Cornelia de Lange syndrome XL 41 50 HNRNPK Au-Kline syndrome AD 14 10 HOXA1 Athabaskan brainstem dysgenesis syndrome, Bosley-Salih-Alorainy AR 4 7 syndrome HRAS Costello syndrome, Congenital myopathy with excess of muscle spindles AD 43 31 JAG1 Alagille syndrome AD 131 610 KDM6A Kabuki syndrome XL 40 69 KMT2D Kabuki syndrome AD 350 670 KRAS* Noonan syndrome, Cardiofaciocutaneous syndrome AD 63 35 https://blueprintgenetics.com/ KYNU Hydroxykynureninuria, Vertebral, cardiac, renal, and limb defects AR 4 7 syndrome 2 LEFTY2* Left-right axis malformations AD 1 3 MED12 Ohdo syndrome, Mental retardation, with Marfanoid habitus, FG XL 29 30 syndrome, Opitz-Kaveggia syndrome, Lujan-Fryns syndrome MED13L Transposition of the great arteries, dextro-looped 1, Mental retardation AD/AR 92 78 and distinctive facial features with or without cardiac defects, Congenital heart defects and intellectual disability, Intellectual disability, autosomal recessive MEIS2 Cleft palate, cardiac defects, and mental retardation (CPCMR) AD 10 18 MMP21 Heterotaxy, visceral, 7 AR 4 18 MYCN Feingold syndrome AD 27 41 MYO18B Klippel-Feil syndrome 4, autosomal recessive, with myopathy and facial AR 2 4 dysmorphism MYRF Congenital heart malformations, Congenital abnormalities of the kidney AD 1 1 and urinary tract NAA15 Congenital heart malformations AD 10 32 NF1* Watson syndrome, Neurofibromatosis, Neurofibromatosis-Noonan AD 1157 2901 syndrome NIPBL Cornelia de Lange syndrome AD 311 425 NKX2-5 Conotruncal heart malformations, Hypothyroidism, congenital AD 45 108 nongoitrous,, Atrial septal defect, Ventricular septal defect 3, Conotruncal heart malformations, variable, Tetralogy of Fallot NKX2-6 Persistent truncus arteriosus, Conotruncal heart malformations AD/AR 2 9 NODAL Heterotaxy, visceral AD 4 15 NONO Mental retardation, X-linked, syndrome 34, Left ventricular non- XL 10 4 compaction cardiomyopathy (LVNC) NOTCH1 Aortic valve disease, Adams-Oliver syndrome AD 56 96 NOTCH2* Alagille syndrome, Hajdu-Cheney syndrome AD 37 70 NR2F2 Congenital heart defects, multiple types, 4 AD 12 16 NSD1 Sotos syndrome, Weaver syndrome, Beckwith-Wiedemann syndrome AD 329 517 PITX2 Axenfeld-Rieger syndrome, Ring dermoid of cornea, AD 23 101 Iridogoniodysgenesis, Peters anomaly PKD1L1 Heterotaxy, visceral, 8, autosomal AR 2 6 PPP1CB# Noonan syndrome-like disorder with loose anagen hair 2 AD 8 11 PRDM6 Patent ductus arteriosus 3, Congenital heart malformations AD 4 3 PRKD1 Congenital heart defects and ectodermal dysplasia AD 2 7 https://blueprintgenetics.com/ PTPN11 Noonan syndrome, Metachondromatosis AD 135 140 PUF60 Short stature, Microcephaly AD 24 30 RAB23# Carpenter syndrome 1 AR 5 15 RAF1 LEOPARD syndrome, Noonan syndrome, Dilated cardiomyopathy (DCM) AD 45 53 RBM10 TARP syndrome XL 12 10 RERE Neurodevelopmental disorder with or without anomalies of the brain, eye, AD 24 24 or heart (NEDBEH) RIT1 Noonan syndrome AD 23 26 SALL4 Acro-renal-ocular syndrome, Duane-radial ray/Okohiro syndrome AD 21 56 SMARCB1 Schwannomatosis, Rhabdoid tumor predisposition syndrome, Coffin-Siris AD 36 118 syndrome 3 SMC1A Cornelia de Lange syndrome XL 73 87 SMC3 Cornelia de Lange syndrome AD 25 21 SOS1 Noonan syndrome AD 44 71 SOS2 Noonan syndrome 9 AD 4 6 STAG2 Congenital heart defects, dysmorphic facial features, and intellectual XL 6 14 developmental disorder STRA6 Microphthalmia, syndromic, Microphthalmia, isolated, with coloboma AR 22 33 TAB2 Congenital heart defects, multiple types, 2 AD 13 31 TBX1 Conotruncal anomaly face syndrome AD 17 72 TBX20* Atrial septal defect 4 AD 4 28 TBX5 Holt-Oram syndrome AD 61 127 TFAP2B Patent ductus arteriosus, nonsyndromic, Char syndrome AD 10 12 TGDS Catel-Manzke syndrome AR 6 7 TLL1 Atrial septal
Recommended publications
  • CEP41 As an ASD Gene Ashok Patowary 1,Soyeonwon2,Shinjioh2,Ryanrnesbitt1, Marilyn Archer1, Debbie Nickerson3, Wendy H

    CEP41 As an ASD Gene Ashok Patowary 1,Soyeonwon2,Shinjioh2,Ryanrnesbitt1, Marilyn Archer1, Debbie Nickerson3, Wendy H

    Patowary et al. Translational Psychiatry (2019) 9:4 https://doi.org/10.1038/s41398-018-0343-z Translational Psychiatry ARTICLE Open Access Family-based exome sequencing and case- control analysis implicate CEP41 as an ASD gene Ashok Patowary 1,SoYeonWon2,ShinJiOh2,RyanRNesbitt1, Marilyn Archer1, Debbie Nickerson3, Wendy H. Raskind1,4, Raphael Bernier1,JiEunLee2,5 and Zoran Brkanac1 Abstract Autism Spectrum Disorder (ASD) is a complex neurodevelopmental disorder with a strong genetic component. Although next-generation sequencing (NGS) technologies have been successfully applied to gene identification in de novo ASD, the genetic architecture of familial ASD remains largely unexplored. Our approach, which leverages the high specificity and sensitivity of NGS technology, has focused on rare variants in familial autism. We used NGS exome sequencing in 26 families with distantly related affected individuals to identify genes with private gene disrupting and missense variants of interest (VOI). We found that the genes carrying VOIs were enriched for biological processes related to cell projection organization and neuron development, which is consistent with the neurodevelopmental hypothesis of ASD. For a subset of genes carrying VOIs, we then used targeted NGS sequencing and gene-based variant burden case-control analysis to test for association with ASD. Missense variants in one gene, CEP41, associated significantly with ASD (p = 6.185e−05). Homozygous gene-disrupting variants in CEP41 were initially found to be responsible for recessive Joubert syndrome. Using a zebrafish model, we evaluated the mechanism by which the 1234567890():,; 1234567890():,; 1234567890():,; 1234567890():,; CEP41 variants might contribute to ASD. We found that CEP41 missense variants affect development of the axonal tract, cranial neural crest migration and social behavior phenotype.
  • Fog2 Is Critical for Cardiac Function and Maintenance of Coronary Vasculature in the Adult Mouse Heart

    Fog2 Is Critical for Cardiac Function and Maintenance of Coronary Vasculature in the Adult Mouse Heart

    Fog2 is critical for cardiac function and maintenance of coronary vasculature in the adult mouse heart Bin Zhou, … , Sergei G. Tevosian, William T. Pu J Clin Invest. 2009;119(6):1462-1476. https://doi.org/10.1172/JCI38723. Research Article Cardiology Aberrant transcriptional regulation contributes to the pathogenesis of both congenital and adult forms of heart disease. While the transcriptional regulator friend of Gata 2 (FOG2) is known to be essential for heart morphogenesis and coronary development, its tissue-specific function has not been previously investigated. Additionally, little is known about the role of FOG2 in the adult heart. Here we used spatiotemporally regulated inactivation of Fog2 to delineate its function in both the embryonic and adult mouse heart. Early cardiomyocyte-restricted loss of Fog2 recapitulated the cardiac and coronary defects of the Fog2 germline murine knockouts. Later cardiomyocyte-restricted loss ofF og2 (Fog2MC) did not result in defects in cardiac structure or coronary vessel formation. However, Fog2MC adult mice had severely depressed ventricular function and died at 8–14 weeks. Fog2MC adult hearts displayed a paucity of coronary vessels, associated with myocardial hypoxia, increased cardiomyocyte apoptosis, and cardiac fibrosis. Induced inactivation of Fog2 in the adult mouse heart resulted in similar phenotypes, as did ablation of the FOG2 interaction with the transcription factor GATA4. Loss of the FOG2 or FOG2-GATA4 interaction altered the expression of a panel of angiogenesis-related genes. Collectively, our data indicate that FOG2 regulates adult heart function and coronary angiogenesis. Find the latest version: https://jci.me/38723/pdf Research article Fog2 is critical for cardiac function and maintenance of coronary vasculature in the adult mouse heart Bin Zhou,1,2 Qing Ma,1 Sek Won Kong,1 Yongwu Hu,1,3 Patrick H.
  • Tall Stature: a Difficult Diagnosis? Cristina Meazza1* , Chiara Gertosio2, Roberta Giacchero3, Sara Pagani1 and Mauro Bozzola1

    Tall Stature: a Difficult Diagnosis? Cristina Meazza1* , Chiara Gertosio2, Roberta Giacchero3, Sara Pagani1 and Mauro Bozzola1

    Meazza et al. Italian Journal of Pediatrics (2017) 43:66 DOI 10.1186/s13052-017-0385-5 REVIEW Open Access Tall stature: a difficult diagnosis? Cristina Meazza1* , Chiara Gertosio2, Roberta Giacchero3, Sara Pagani1 and Mauro Bozzola1 Abstract Referral for an assessment of tall stature is less common than for short stature. Tall stature is defined as a height more than two standard deviations above the mean for age. The majority of subjects with tall stature show a familial tall stature or a constitutional advance of growth (CAG), which is a diagnosis of exclusion. After a careful physical evaluation, tall subjects may be divided into two groups: tall subjects with normal appearance and tall subjects with abnormal appearance. In the case of normal appearance, the paediatric endocrinologist will have to evaluate the growth rate. If it is normal for age and sex, the subject may be classified as having familial tall stature, CAG or obese subject, while if the growth rate is increased it is essential to evaluate pubertal status and thyroid status. Tall subjects with abnormal appearance and dysmorphisms can be classified into those with proportionate and disproportionate syndromes. A careful physical examination and an evaluation of growth pattern are required before starting further investigations. Physicians should always search for a pathological cause of tall stature, although the majority of children are healthy and they generally do not need treatment to cease growth progression. The most accepted and effective treatment for an excessive height prediction is inducing puberty early and leading to a complete fusion of the epiphyses and achievement of final height, using testosterone in males and oestrogens in females.
  • Genetic Investigation of Patients with Tall Stature

    Genetic Investigation of Patients with Tall Stature

    2 182 E Vasco de Albuquerque Genetic investigation of tall 182:2 139–147 Clinical Study Albuquerque and others stature patients Genetic investigation of patients with tall stature Edoarda Vasco de Albuquerque Albuquerque1, Mariana Ferreira de Assis Funari2, Elisângela Pereira de Souza Quedas1, Rachel Sayuri Honjo Kawahira3, Raquel Soares Jallad4, Thaís Kataoka Homma1, Regina Matsunaga Martin2,5, Vinicius Nahime Brito2, Alexsandra Christianne Malaquias1,6, Antonio Marcondes Lerario1,7, Carla Rosenberg8, Ana Cristina Victorino Krepischi8, Chong Ae Kim3, Ivo Jorge Prado Arnhold2 and Alexander Augusto de Lima Jorge1 1Unidade de Endocrinologia Genética (LIM25), 2Unidade de Endocrinologia do Desenvolvimento, Laboratório de Hormônios e Genética Molecular (LIM42), Hospital das Clínicas da Faculdade de Medicina, Universidade de São Paulo (USP), São Paulo, Brasil, 3Unidade de Genética do Instituto da Criança, Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brasil, 4Unidade de Neuroendocrinologia, 5Unidade de Doenças Osteometabólicas, Hospital das Clínicas da Faculdade de Medicina, Universidade de São Paulo (USP), São Paulo, Brasil, 6Unidade de Endocrinologia Pediátrica, Correspondence Departamento de Pediatria, Irmandade da Santa Casa de Misericórdia de São Paulo, São Paulo, Brasil, 7Division of should be addressed Metabolism, Endocrinology and Diabetes, Department of Internal Medicine, University of Michigan, Ann Arbor, to A A L Jorge Michigan, USA, and 8Instituto de Biociências (IB), Universidade de São Paulo (USP), São Paulo, Brasil Email [email protected] Abstract Context: Patients with tall stature often remain undiagnosed after clinical investigation and few studies have genetically assessed this group, most of them without a systematic approach. Objective: To assess prospectively a group of individuals with tall stature, with and without syndromic features, and to establish a molecular diagnosis for their growth disorder.
  • Pulmonary Arteriopathy in Patients with Mild Pulmonary Valve Abnormality Without Pulmonary Hypertension Or Intracardiac Shunt Karam Obeid1*, Subeer K

    Pulmonary Arteriopathy in Patients with Mild Pulmonary Valve Abnormality Without Pulmonary Hypertension Or Intracardiac Shunt Karam Obeid1*, Subeer K

    Original Scientific Article Journal of Structural Heart Disease, June 2018, Received: September 13, 2017 Volume 4, Issue 3:79-84 Accepted: September 27, 2017 Published online: June 2018 DOI: https://doi.org/10.12945/j.jshd.2018.040.18 Pulmonary Arteriopathy in Patients with Mild Pulmonary Valve Abnormality without Pulmonary Hypertension or Intracardiac Shunt Karam Obeid1*, Subeer K. Wadia, MD2, Gentian Lluri, MD, PhD2, Cherise Meyerson, MD3, Gregory A. Fishbein, MD3, Leigh C. Reardon, MD2, Jamil Aboulhosn, MD2 1 Department of Biological Sciences, Old Dominion University, Norfolk, Virginia, USA 2 Department of Internal Medicine, Ahmanson/UCLA Adult Congenital Heart Disease Center, Los Angeles, California, USA 3 Department of Pathology, Ronald Reagan/UCLA Medical Center, Los Angeles, California, USA Abstract benign course without episodes of dissection or rup- Background: The natural history of pulmonary artery ture despite 6/11 patients with PAA ≥ 5 cm. PA dilation aneurysms (PAA) without pulmonary hypertension, progresses slowly over time and does not appear to intracardiac shunt or significant pulmonary valvular cause secondary events. Echocardiography correlates disease has not been well studied. This study looks to well with magnetic resonance imaging and computed describe the outcome of a cohort of adults with PAA tomography and is useful in measuring PAA over time. without significant pulmonic regurgitation and steno- Copyright © 2018 Science International Corp. sis. Imaging modalities utilized to evaluate pulmonary artery (PA) size and valvular pathology are reviewed. Key Words Methods: Patients with PAA followed at the Ahmanson/ Pulmonary artery aneurysm • Pulmonary stenosis • UCLA Adult Congenital Heart Disease Center were in- Pulmonary hypertension • Aortic aneurysm cluded in this retrospective analysis.
  • Program Nr: 1 from the 2004 ASHG Annual Meeting Mutations in A

    Program Nr: 1 from the 2004 ASHG Annual Meeting Mutations in A

    Program Nr: 1 from the 2004 ASHG Annual Meeting Mutations in a novel member of the chromodomain gene family cause CHARGE syndrome. L.E.L.M. Vissers1, C.M.A. van Ravenswaaij1, R. Admiraal2, J.A. Hurst3, B.B.A. de Vries1, I.M. Janssen1, W.A. van der Vliet1, E.H.L.P.G. Huys1, P.J. de Jong4, B.C.J. Hamel1, E.F.P.M. Schoenmakers1, H.G. Brunner1, A. Geurts van Kessel1, J.A. Veltman1. 1) Dept Human Genetics, UMC Nijmegen, Nijmegen, Netherlands; 2) Dept Otorhinolaryngology, UMC Nijmegen, Nijmegen, Netherlands; 3) Dept Clinical Genetics, The Churchill Hospital, Oxford, United Kingdom; 4) Children's Hospital Oakland Research Institute, BACPAC Resources, Oakland, CA. CHARGE association denotes the non-random occurrence of ocular coloboma, heart defects, choanal atresia, retarded growth and development, genital hypoplasia, ear anomalies and deafness (OMIM #214800). Almost all patients with CHARGE association are sporadic and its cause was unknown. We and others hypothesized that CHARGE association is due to a genomic microdeletion or to a mutation in a gene affecting early embryonic development. In this study array- based comparative genomic hybridization (array CGH) was used to screen patients with CHARGE association for submicroscopic DNA copy number alterations. De novo overlapping microdeletions in 8q12 were identified in two patients on a genome-wide 1 Mb resolution BAC array. A 2.3 Mb region of deletion overlap was defined using a tiling resolution chromosome 8 microarray. Sequence analysis of genes residing within this critical region revealed mutations in the CHD7 gene in 10 of the 17 CHARGE patients without microdeletions, including 7 heterozygous stop-codon mutations.
  • Functional Characterization of Alternative Splice Variants of The

    Functional Characterization of Alternative Splice Variants of The

    Functional characterization of alternative splice variants of the Drosophila GATA transcription factor serpent containing either one or two zinc finger domains Douaa Moussalem To cite this version: Douaa Moussalem. Functional characterization of alternative splice variants of the Drosophila GATA transcription factor serpent containing either one or two zinc finger domains. Genetics. Université Paul Sabatier - Toulouse III, 2020. English. NNT : 2020TOU30138. tel-03162582 HAL Id: tel-03162582 https://tel.archives-ouvertes.fr/tel-03162582 Submitted on 8 Mar 2021 HAL is a multi-disciplinary open access L’archive ouverte pluridisciplinaire HAL, est archive for the deposit and dissemination of sci- destinée au dépôt et à la diffusion de documents entific research documents, whether they are pub- scientifiques de niveau recherche, publiés ou non, lished or not. The documents may come from émanant des établissements d’enseignement et de teaching and research institutions in France or recherche français ou étrangers, des laboratoires abroad, or from public or private research centers. publics ou privés. THÈSE En vue de l’obtention du DOCTORAT DE L’UNIVERSITÉ DE TOULOUSE Délivré par l'Université Toulouse 3 - Paul Sabatier Présentée et soutenue par Douaa MOUSSALEM Le 12 octobre 2020 Titre : Functional characterization of alternative splice variants of the Drosophila GATA transcription factor Serpent containing either one or two zinc finger domains. Ecole doctorale : BSB - Biologie, Santé, Biotechnologies Spécialité : GENETIQUE MOLECULAIRE Unité de recherche : CBD - Centre de Biologie du Développement Thèse dirigée par Marc HAENLIN et Dani OSMAN Jury M. David CRIBBS, Président Mme Annarita MICCIO, Rapporteure Mme Kyra CAMPBELL, Rapporteure M. Samir MERABET, Rapporteur M. Marc HAENLIN, Directeur de thèse M.
  • Profiling Data

    Profiling Data

    Compound Name DiscoveRx Gene Symbol Entrez Gene Percent Compound Symbol Control Concentration (nM) JNK-IN-8 AAK1 AAK1 69 1000 JNK-IN-8 ABL1(E255K)-phosphorylated ABL1 100 1000 JNK-IN-8 ABL1(F317I)-nonphosphorylated ABL1 87 1000 JNK-IN-8 ABL1(F317I)-phosphorylated ABL1 100 1000 JNK-IN-8 ABL1(F317L)-nonphosphorylated ABL1 65 1000 JNK-IN-8 ABL1(F317L)-phosphorylated ABL1 61 1000 JNK-IN-8 ABL1(H396P)-nonphosphorylated ABL1 42 1000 JNK-IN-8 ABL1(H396P)-phosphorylated ABL1 60 1000 JNK-IN-8 ABL1(M351T)-phosphorylated ABL1 81 1000 JNK-IN-8 ABL1(Q252H)-nonphosphorylated ABL1 100 1000 JNK-IN-8 ABL1(Q252H)-phosphorylated ABL1 56 1000 JNK-IN-8 ABL1(T315I)-nonphosphorylated ABL1 100 1000 JNK-IN-8 ABL1(T315I)-phosphorylated ABL1 92 1000 JNK-IN-8 ABL1(Y253F)-phosphorylated ABL1 71 1000 JNK-IN-8 ABL1-nonphosphorylated ABL1 97 1000 JNK-IN-8 ABL1-phosphorylated ABL1 100 1000 JNK-IN-8 ABL2 ABL2 97 1000 JNK-IN-8 ACVR1 ACVR1 100 1000 JNK-IN-8 ACVR1B ACVR1B 88 1000 JNK-IN-8 ACVR2A ACVR2A 100 1000 JNK-IN-8 ACVR2B ACVR2B 100 1000 JNK-IN-8 ACVRL1 ACVRL1 96 1000 JNK-IN-8 ADCK3 CABC1 100 1000 JNK-IN-8 ADCK4 ADCK4 93 1000 JNK-IN-8 AKT1 AKT1 100 1000 JNK-IN-8 AKT2 AKT2 100 1000 JNK-IN-8 AKT3 AKT3 100 1000 JNK-IN-8 ALK ALK 85 1000 JNK-IN-8 AMPK-alpha1 PRKAA1 100 1000 JNK-IN-8 AMPK-alpha2 PRKAA2 84 1000 JNK-IN-8 ANKK1 ANKK1 75 1000 JNK-IN-8 ARK5 NUAK1 100 1000 JNK-IN-8 ASK1 MAP3K5 100 1000 JNK-IN-8 ASK2 MAP3K6 93 1000 JNK-IN-8 AURKA AURKA 100 1000 JNK-IN-8 AURKA AURKA 84 1000 JNK-IN-8 AURKB AURKB 83 1000 JNK-IN-8 AURKB AURKB 96 1000 JNK-IN-8 AURKC AURKC 95 1000 JNK-IN-8
  • Shovlin Wilmshurst and Jackson.Pdf

    Shovlin Wilmshurst and Jackson.Pdf

    Eur Respir Mon 2011; 54: 218–245. DOI: 10.1183/1025448x.10008410 Pulmonary arteriovenous malformations and other pulmonary aspects of hereditary haemorrhagic telangiectasia Claire L Shovlin, 1 2 Peter Wilmshurst 3 4 and James E. Jackson 5 1NHLI Cardiovascular Sciences, Imperial College, London, UK. 2Respiratory Medicine, 5Imaging, Hammersmith Hospital, Imperial College Healthcare NHS Trust, London UK. 3 Department of Cardiology, Royal Shrewsbury Hospital, UK; 4 University of Keele, UK Corresponding author: Dr Claire L. Shovlin PhD FRCP, HHTIC London, Respiratory Medicine, Hammersmith Hospital, Du Cane Rd, London, W12 0NN, UK. Phone (44) 208 383 4831; Fax (44) 208 383 1640; [email protected] CLS and JEJ acknowledge support from the NIHR Biomedical Research Centre Funding Scheme. The authors have no conflicts of interest to declare KEY WORDS: Contrast echocardiography, diving, hypoxaemia, pulmonary hypertension, stroke. 1 SUMMARY: Pulmonary arteriovenous malformations (PAVMs) are vascular structures that provide a direct capillary-free communication between the pulmonary and systemic circulations. The majority of patients have no PAVM-related symptoms, but are at risk of major complications that can be prevented by appropriate interventions. More than 90% of PAVMs occur as part of hereditary haemorrhagic telangiectasia (HHT), the genetic condition most commonly recognised by nosebleeds, anaemia due to chronic haemorrhage, and/or the presence of arteriovenous malformations in pulmonary, hepatic or cerebral circulations. Patients with HHT are also at higher risk of pulmonary hypertension and pulmonary embolic disease, management of which can be compounded by other aspects of their HHT. This chapter primarily addresses PAVMs and pulmonary HHT in the clinical setting, in order to improve patient care.
  • Megalencephaly and Macrocephaly

    Megalencephaly and Macrocephaly

    277 Megalencephaly and Macrocephaly KellenD.Winden,MD,PhD1 Christopher J. Yuskaitis, MD, PhD1 Annapurna Poduri, MD, MPH2 1 Department of Neurology, Boston Children’s Hospital, Boston, Address for correspondence Annapurna Poduri, Epilepsy Genetics Massachusetts Program, Division of Epilepsy and Clinical Electrophysiology, 2 Epilepsy Genetics Program, Division of Epilepsy and Clinical Department of Neurology, Fegan 9, Boston Children’s Hospital, 300 Electrophysiology, Department of Neurology, Boston Children’s Longwood Avenue, Boston, MA 02115 Hospital, Boston, Massachusetts (e-mail: [email protected]). Semin Neurol 2015;35:277–287. Abstract Megalencephaly is a developmental disorder characterized by brain overgrowth secondary to increased size and/or numbers of neurons and glia. These disorders can be divided into metabolic and developmental categories based on their molecular etiologies. Metabolic megalencephalies are mostly caused by genetic defects in cellular metabolism, whereas developmental megalencephalies have recently been shown to be caused by alterations in signaling pathways that regulate neuronal replication, growth, and migration. These disorders often lead to epilepsy, developmental disabilities, and Keywords behavioral problems; specific disorders have associations with overgrowth or abnor- ► megalencephaly malities in other tissues. The molecular underpinnings of many of these disorders are ► hemimegalencephaly now understood, providing insight into how dysregulation of critical pathways leads to ►
  • De Novo EIF2AK1 and EIF2AK2 Variants Are Associated with Developmental Delay, Leukoencephalopathy, and Neurologic Decompensation

    De Novo EIF2AK1 and EIF2AK2 Variants Are Associated with Developmental Delay, Leukoencephalopathy, and Neurologic Decompensation

    bioRxiv preprint doi: https://doi.org/10.1101/757039; this version posted September 16, 2019. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission. De novo EIF2AK1 and EIF2AK2 variants are associated with developmental delay, leukoencephalopathy, and neurologic decompensation Dongxue Mao1,2, Chloe M. Reuter3,4, Maura R.Z. Ruzhnikov5,6, Anita E. Beck7, Emily G. Farrow8,9,10, Lisa T. Emrick1,11,12,13, Jill A. Rosenfeld12, Katherine M. Mackenzie5, Laurie Robak2,12,13, Matthew T. Wheeler3,14, Lindsay C. Burrage12,13, Mahim Jain15, Pengfei Liu12, Daniel Calame11,13, Sebastien Küry17,18, Martin Sillesen19, Klaus Schmitz-Abe20, Davide Tonduti21, Luigina Spaccini22, Maria Iascone23, Casie A. Genetti20, Madeline Graf16, Alyssa Tran12, Mercedes Alejandro12, Undiagnosed Diseases Network, Brendan H. Lee12,13, Isabelle Thiffault8,9,24, Pankaj B. Agrawal#,20, Jonathan A. Bernstein#,3,25, Hugo J. Bellen#,2,12,26,27,28, Hsiao- Tuan Chao#,1,2,11,12,13,28,27,29 #Correspondence should be addressed: [email protected] (P.A.), [email protected] (J.A.B.), [email protected] (H.J.B.), [email protected] (H.T.C.) 1Department of Pediatrics, Baylor College of Medicine (BCM), Houston, TX 2Jan and Dan Duncan Neurological Research Institute, Texas Children’s Hospital, Houston, TX 3Stanford Center for Undiagnosed Diseases, Stanford University, Stanford, CA 4Stanford Center for Inherited Cardiovascular Disease, Division of Cardiovascular Medicine,
  • Saethre-Chotzen Syndrome

    Saethre-Chotzen Syndrome

    Saethre-Chotzen syndrome Authors: Professor L. Clauser1 and Doctor M. Galié Creation Date: June 2002 Update: July 2004 Scientific Editor: Professor Raoul CM. Hennekam 1Department of craniomaxillofacial surgery, St. Anna Hospital and University, Corso Giovecca, 203, 44100 Ferrara, Italy. [email protected] Abstract Keywords Disease name and synonyms Excluded diseases Definition Prevalence Management including treatment Etiology Diagnostic methods Genetic counseling Antenatal diagnosis Unresolved questions References Abstract Saethre-Chotzen Syndrome (SCS) is an inherited craniosynostotic condition, with both premature fusion of cranial sutures (craniostenosis) and limb abnormalities. The most common clinical features, present in more than a third of patients, consist of coronal synostosis, brachycephaly, low frontal hairline, facial asymmetry, hypertelorism, broad halluces, and clinodactyly. The estimated birth incidence is 1/25,000 to 1/50,000 but because the phenotype can be very mild, the entity is likely to be underdiagnosed. SCS is inherited as an autosomal dominant trait with a high penetrance and variable expression. The TWIST gene located at chromosome 7p21-p22, is responsible for SCS and encodes a transcription factor regulating head mesenchyme cell development during cranial tube formation. Some patients with an overlapping SCS phenotype have mutations in the FGFR3 (fibroblast growth factor receptor 3) gene; especially the Pro250Arg mutation in FGFR3 (Muenke syndrome) can resemble SCS to a great extent. Significant intrafamilial