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  1 / 1822 MEDLINE  
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[PMID]:29465581
[Au] Autor:Shi H; Wang Z
[Ad] Endereço:Key Laboratory of Thrombosis and Hemostasis of Ministry of Health, Jiangsu Institute of Hematology, The First Affiliated Hospital of Soochow University.
[Ti] Título:Atypical microdeletion in 22q11 deletion syndrome reveals new candidate causative genes: A case report and literature review.
[So] Source:Medicine (Baltimore);97(8):e9936, 2018 Feb.
[Is] ISSN:1536-5964
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:RATIONALE: 22q11 deletion syndrome, the most common chromosomal microdeletion disease, is caused by megabase-sized deletions on chromosome 22q11.2. It is characterized by a wide spectrum of congenital anomalies in velopharyngeal and facial, cardiac, genitourinary, vertebroskeletal, respiratory, digestive, and central nervous systems. Phenotype-genotype studies have revealed several causative genes that regulate the development of the third and fourth pharyngeal arches in human. However, the exact pathogenesis of this syndrome remains unknown. Herein, we report a case of 22q11 deletion syndrome with an atypical microdeletion of 125 kb. PATIENT CONCERNS: A 15-year-old Chinese girl presented with symptoms of facial dysmorphia, cardiac defects, velopharyngeal insufficiency, splenomegaly, immunodeficiency, and thrombocytopenia. DIAGNOSES: Microarray analysis revealed a 22q11.23 deletion of 125 kb (chromosome 22: 24276973-24402263), suggesting the diagnosis of 22q11 deletion syndrome. The haploinsufficient genes included GSTT2B, GSTT2, DDTL, DDT, GSTTP1, LOC391322, GSTT1, and GSTTP2. INTERVENTIONS: The patient was administrated glucocorticoids and calcium supplements. OUTCOMES: No epistaxis or petechiae episode occurred during the follow-up; her platelet count ranged between 60 × 10 and 80 × 10/L. LESSONS: Although none of the previous reported causative genes were affected in the patient, her clinical manifestations were typical of 22q11 deletion syndrome, apart from her progressive splenomegaly. This case indicated 8 new candidate pathogenic genes for 22q11 deletion syndrome. Given that the loss of these genes was sufficient to induce 22q11DS defects, whether these genes directly influence the pathogenesis of 22q11DS or through interactions with known hotspot mutations is worthy of research.
[Mh] Termos MeSH primário: Síndrome de DiGeorge/genética
[Mh] Termos MeSH secundário: Adolescente
Deleção Cromossômica
Cromossomos Humanos Par 22/genética
Feminino
Seres Humanos
[Pt] Tipo de publicação:CASE REPORTS; JOURNAL ARTICLE; REVIEW
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180302
[Lr] Data última revisão:
180302
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:180222
[St] Status:MEDLINE
[do] DOI:10.1097/MD.0000000000009936


  2 / 1822 MEDLINE  
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[PMID]:29281626
[Au] Autor:Lin JR; Zhang Q; Cai Y; Morrow BE; Zhang ZD
[Ad] Endereço:Department of Genetics, Albert Einstein College of Medicine, Bronx, New York, United States of America.
[Ti] Título:Integrated rare variant-based risk gene prioritization in disease case-control sequencing studies.
[So] Source:PLoS Genet;13(12):e1007142, 2017 12.
[Is] ISSN:1553-7404
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Rare variants of major effect play an important role in human complex diseases and can be discovered by sequencing-based genome-wide association studies. Here, we introduce an integrated approach that combines the rare variant association test with gene network and phenotype information to identify risk genes implicated by rare variants for human complex diseases. Our data integration method follows a 'discovery-driven' strategy without relying on prior knowledge about the disease and thus maintains the unbiased character of genome-wide association studies. Simulations reveal that our method can outperform a widely-used rare variant association test method by 2 to 3 times. In a case study of a small disease cohort, we uncovered putative risk genes and the corresponding rare variants that may act as genetic modifiers of congenital heart disease in 22q11.2 deletion syndrome patients. These variants were missed by a conventional approach that relied on the rare variant association test alone.
[Mh] Termos MeSH primário: Predisposição Genética para Doença
Variação Genética
Estudo de Associação Genômica Ampla/métodos
Análise de Sequência de DNA/métodos
[Mh] Termos MeSH secundário: Estudos de Casos e Controles
Simulação por Computador
Interpretação Estatística de Dados
Síndrome de DiGeorge/genética
Seres Humanos
Fenótipo
Fatores de Risco
Análise de Sequência de DNA/estatística & dados numéricos
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL; RESEARCH SUPPORT, NON-U.S. GOV'T
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180227
[Lr] Data última revisão:
180227
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171228
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pgen.1007142


  3 / 1822 MEDLINE  
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[PMID]:29178641
[Au] Autor:Benn P; Iyengar S; Crowley TB; Zackai EH; Burrows EK; Moshkevich S; McDonald-McGinn DM; Sullivan KE; Demko Z
[Ad] Endereço:University of Connecticut Health Center, Farmington, Connecticut.
[Ti] Título:Pediatric healthcare costs for patients with 22q11.2 deletion syndrome.
[So] Source:Mol Genet Genomic Med;5(6):631-638, 2017 11.
[Is] ISSN:2324-9269
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: The 22q11.2 deletion syndrome is a variably expressed disorder that can include cardiac, palate, and other physical abnormalities, immunodeficiency, and hypocalcemia. Because of the extreme variability in phenotype, there has been no available estimate of the total medical expenditure associated with the average case. METHODS: We have developed a model to estimate the cost from the time of diagnosis to age 20. Costs were based on patients seen at a specialty center but also considered those components of care expected to have been provided by external healthcare facilities. Expense was based on billed medical charges extracted from the electronic medical billing system for all patients with a diagnosis of DiGeorge or velocardiofacial syndrome from 1993-2015. Expenditures included maternal prenatal care directly related to an affected pregnancy, molecular/cytogenetic diagnosis, consultations, surgery, and/or other treatment and management. Most mental health services (except inpatient), therapy related to cognitive, behavioral, speech, pharmacy, and nonmedical costs (special education, vocational, respite, lost earnings) were not included. RESULTS: Data were available for 642 patients with 50.7% diagnosed prenatally or in the first year of life. The average cost for a patient was $727,178. Costs were highest for patients ascertained prenatally ($2,599,955) or in the first year of life ($1,043,096), those with cardiac abnormalities or referred for cardiac evaluation ($751,535), and patients with low T-cell counts ($1,382,222). CONCLUSION: This study demonstrates that there are significant medical costs associated with 22q11.2 deletion syndrome.
[Mh] Termos MeSH primário: Cromossomos Humanos Par 22
Síndrome de DiGeorge/economia
Custos de Cuidados de Saúde
[Mh] Termos MeSH secundário: Deleção Cromossômica
Síndrome de DiGeorge/diagnóstico
Síndrome de DiGeorge/genética
Seres Humanos
Modelos Teóricos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180207
[Lr] Data última revisão:
180207
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171128
[St] Status:MEDLINE
[do] DOI:10.1002/mgg3.310


  4 / 1822 MEDLINE  
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[PMID]:29199443
[Au] Autor:Hua X; Diggelmann H; Jalukar V; Turek JW; Pagedar NA
[Ad] Endereço:1 Department of Otolaryngology-Head and Neck Surgery, University of Iowa Hospitals and Clinics, Iowa City, Iowa, USA.
[Ti] Título:Successful Prediction of a Left Nonrecurrent Laryngeal Nerve in a Patient With Right-Sided Aorta and Aberrant Left Subclavian Artery.
[So] Source:Ann Otol Rhinol Laryngol;127(2):124-127, 2018 Feb.
[Is] ISSN:1943-572X
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Left nonrecurrent laryngeal nerve (LNRLN) is an extremely rare anatomic variant. The development of such anatomic variation requires the regression of both the fourth (aortic arch) and sixth (ductus arteriosus, DA) arches on the left side. Preoperative prediction of this variant is difficult but might reduce risk of nerve injury. METHODS: A 34-year-old female was indicated for thyroidectomy for a 2.4 cm follicular neoplasm and Graves' disease. Due to a positive medical history of 22q11.2 microdeletion and unexplained left vocal cord paralysis, a preoperative chest computed tomography (CT) scan was obtained and revealed a right-sided aorta (RSA) and aberrant left subclavian artery (ALSA) without Kommerell's diverticulum. A left-sided NRLN was then highly suspected. RESULTS: Thyroidectomy was performed under general anesthesia with the utilization of intraoperative laryngeal nerve monitoring. A LNRLN was confirmed intraoperatively. CONCLUSIONS: Right-sided aorta and ALSA indicate embryologic regression of the left fourth primitive aortic arch. The absence of Kommerell's diverticulum at the origin of the ALSA indicates the lack of high-pressure blood flow from the pulmonary artery to the ALSA through the ductus arteriosus during embryogenesis, suggesting the embryologic regression of the left sixth primitive aortic arch. The presence of all 3 radiologic features thus highly suggests the possibility of a LNRLN.
[Mh] Termos MeSH primário: Aorta Torácica/anormalidades
Carcinoma Papilar, Variante Folicular/cirurgia
Doença de Graves/cirurgia
Nervos Laríngeos/anormalidades
Artéria Subclávia/anormalidades
Neoplasias da Glândula Tireoide/cirurgia
Tireoidectomia
[Mh] Termos MeSH secundário: Adulto
Aorta Torácica/patologia
Carcinoma Papilar, Variante Folicular/genética
Carcinoma Papilar, Variante Folicular/patologia
Síndrome de DiGeorge/genética
Síndrome de DiGeorge/patologia
Feminino
Doença de Graves/genética
Doença de Graves/patologia
Seres Humanos
Nervos Laríngeos/patologia
Artéria Subclávia/patologia
Neoplasias da Glândula Tireoide/genética
Neoplasias da Glândula Tireoide/patologia
Tomografia Computadorizada por Raios X
[Pt] Tipo de publicação:CASE REPORTS; JOURNAL ARTICLE
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180123
[Lr] Data última revisão:
180123
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:171205
[St] Status:MEDLINE
[do] DOI:10.1177/0003489417744318


  5 / 1822 MEDLINE  
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[PMID]:29287846
[Au] Autor:Verheij E; Speleman L; Mink van der Molen AB; Thomeer HGXM
[Ad] Endereço:Department of Otorhinolaryngology - Head and Neck Surgery, University Medical Center Utrecht, Utrecht University, The Netherlands; Brain Center Rudolf Magnus, University Medical Center Utrecht, The Netherlands. Electronic address: e.verheij-5@umcutrecht.nl.
[Ti] Título:Congenital respiratory tract disorders in 22q11.2 deletion syndrome.
[So] Source:Int J Pediatr Otorhinolaryngol;104:1-4, 2018 Jan.
[Is] ISSN:1872-8464
[Cp] País de publicação:Ireland
[La] Idioma:eng
[Ab] Resumo:OBJECTIVE: Respiratory tract disorders have been reported in patients with 22q11.2 deletion syndrome, however infrequently. This study describes the respiratory tract disorders encountered in a cohort of 278 patients with 22q11.2 deletion syndrome. METHODS: We conducted a retrospective, cross-sectional, study at a single tertiary referral center. We identified the patients with 22q11.2 deletion syndrome and with an upper and/or lower respiratory tract disorder at our otorhinolaryngologic department. The different disorders were described. RESULTS: Out of 278 patients referred to the otorhinolaryngologic department, we identified 14 patients with a laryngeal and/or tracheal disorder. Nine patients had more than one congenital disorder in this anatomical area. Disorders included a choanal stenosis (n = 1), laryngeal web (n = 5), laryngeal cleft (n = 2), subglottic stenosis (n = 3), pharyngo-, laryngo-, tracheo- and/or bronchomalacia (n = 11) and tracheal stenosis (n = 1). CONCLUSION: Different types of respiratory tract disorders can be present in patients with 22q11.2 deletion syndrome. Clinicians should be aware of this clinical association for timely and accurate diagnosis and treatment. In addition, the diagnosis 22q11.2 deletion syndrome should be considered in patients presenting with a congenital respiratory tract disorder.
[Mh] Termos MeSH primário: Síndrome de DiGeorge/complicações
Doenças Respiratórias/epidemiologia
[Mh] Termos MeSH secundário: Pré-Escolar
Cromossomos Humanos Par 22
Estudos Transversais
Síndrome de DiGeorge/genética
Feminino
Seres Humanos
Lactente
Recém-Nascido
Masculino
Doenças Respiratórias/congênito
Estudos Retrospectivos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180116
[Lr] Data última revisão:
180116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171231
[St] Status:MEDLINE


  6 / 1822 MEDLINE  
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[PMID]:28448680
[Au] Autor:Wither RG; Borlot F; MacDonald A; Butcher NJ; Chow EWC; Bassett AS; Andrade DM
[Ad] Endereço:Division of Neurology, Department of Medicine, Toronto Western Hospital, Krembil Neuroscience Centre, University of Toronto, Toronto, Ontario, Canada.
[Ti] Título:22q11.2 deletion syndrome lowers seizure threshold in adult patients without epilepsy.
[So] Source:Epilepsia;58(6):1095-1101, 2017 06.
[Is] ISSN:1528-1167
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:OBJECTIVE: Previous studies examining seizures in patients with 22q11.2 deletion syndrome (22q11.2DS) have focused primarily on children and adolescents. In this study we investigated the prevalence and characteristics of seizures and epilepsy in an adult 22q11.2DS population. METHODS: The medical records of 202 adult patients with 22q11.2DS were retrospectively reviewed for documentation of seizures, electroencephalography (EEG) reports, and magnetic resonance imaging (MRI) findings. Epilepsy status was assigned in accordance with 2010 International League Against Epilepsy Classification. RESULTS: Of 202 patients, 32 (15.8%) had a documented history of seizure. Of these 32, 23 (71.8%) had acute symptomatic seizures, usually associated with hypocalcemia and/or antipsychotic or antidepressant use. Nine patients (9/32, 28%; 9/202, 4%) met diagnostic criteria for epilepsy. Two patients had genetic generalized epilepsy; two patients had focal seizures of unknown etiology; two had epilepsy due to malformations of cortical development; in two the epilepsy was due to acquired structural changes; and in one patient the epilepsy could not be further classified. SIGNIFICANCE: Similarly to children, the prevalence of epilepsy and acute symptomatic seizures in adults with 22q11.2DS is higher than in the general population. Hypocalcemia continues to be a risk factor for adults, but differently from kids, the main cause of seizures in adults with 22q11.2DS is exposure to antipsychotics and antidepressants. Further prospective studies are warranted to investigate how 22q11.2 microdeletion leads to an overall decreased seizure threshold.
[Mh] Termos MeSH primário: Anormalidades Múltiplas/genética
Anormalidades Múltiplas/fisiopatologia
Síndrome de DiGeorge/genética
Síndrome de DiGeorge/fisiopatologia
Eletroencefalografia
Epilepsia/genética
Epilepsia/fisiopatologia
Convulsões/genética
Convulsões/fisiopatologia
Processamento de Sinais Assistido por Computador
[Mh] Termos MeSH secundário: Anormalidades Múltiplas/diagnóstico
Adolescente
Adulto
Idade de Início
Deleção Cromossômica
Cromossomos Humanos Par 22/genética
Estudos Transversais
Síndrome de DiGeorge/diagnóstico
Epilepsia/diagnóstico
Feminino
Seres Humanos
Hipocalcemia/complicações
Hipocalcemia/fisiopatologia
Imagem por Ressonância Magnética
Masculino
Meia-Idade
Estudos Retrospectivos
Fatores de Risco
Convulsões/diagnóstico
Adulto Jovem
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Em] Mês de entrada:1707
[Cu] Atualização por classe:180107
[Lr] Data última revisão:
180107
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170428
[St] Status:MEDLINE
[do] DOI:10.1111/epi.13748


  7 / 1822 MEDLINE  
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[PMID]:28965848
[Au] Autor:Demaerel W; Hestand MS; Vergaelen E; Swillen A; López-Sánchez M; Pérez-Jurado LA; McDonald-McGinn DM; Zackai E; Emanuel BS; Morrow BE; Breckpot J; Devriendt K; Vermeesch JR; International 22q11.2 Brain and Behavior Consortium
[Ad] Endereço:Department of Human Genetics, Katholieke Universiteit Leuven, Leuven, Belgium.
[Ti] Título:Nested Inversion Polymorphisms Predispose Chromosome 22q11.2 to Meiotic Rearrangements.
[So] Source:Am J Hum Genet;101(4):616-622, 2017 Oct 05.
[Is] ISSN:1537-6605
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Inversion polymorphisms between low-copy repeats (LCRs) might predispose chromosomes to meiotic non-allelic homologous recombination (NAHR) events and thus lead to genomic disorders. However, for the 22q11.2 deletion syndrome (22q11.2DS), the most common genomic disorder, no such inversions have been uncovered as of yet. Using fiber-FISH, we demonstrate that parents transmitting the de novo 3 Mb LCR22A-D 22q11.2 deletion, the reciprocal duplication, and the smaller 1.5 Mb LCR22A-B 22q11.2 deletion carry inversions of LCR22B-D or LCR22C-D. Hence, the inversions predispose chromosome 22q11.2 to meiotic rearrangements and increase the individual risk for transmitting rearrangements. Interestingly, the inversions are nested or flanking rather than coinciding with the deletion or duplication sizes. This finding raises the possibility that inversions are a prerequisite not only for 22q11.2 rearrangements but also for all NAHR-mediated genomic disorders.
[Mh] Termos MeSH primário: Inversão Cromossômica
Síndrome de DiGeorge/genética
Predisposição Genética para Doença
Meiose
Polimorfismo de Nucleotídeo Único
[Mh] Termos MeSH secundário: Deleção Cromossômica
Variações do Número de Cópias de DNA
Síndrome de DiGeorge/patologia
Recombinação Homóloga
Seres Humanos
Hibridização in Situ Fluorescente/métodos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171016
[Lr] Data última revisão:
171016
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171003
[St] Status:MEDLINE


  8 / 1822 MEDLINE  
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[PMID]:28869582
[Au] Autor:Zaremba JD; Diamantopoulou A; Danielson NB; Grosmark AD; Kaifosh PW; Bowler JC; Liao Z; Sparks FT; Gogos JA; Losonczy A
[Ad] Endereço:Department of Neuroscience, Columbia University, New York, New York, USA.
[Ti] Título:Impaired hippocampal place cell dynamics in a mouse model of the 22q11.2 deletion.
[So] Source:Nat Neurosci;20(11):1612-1623, 2017 Nov.
[Is] ISSN:1546-1726
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Hippocampal place cells represent the cellular substrate of episodic memory. Place cell ensembles reorganize to support learning but must also maintain stable representations to facilitate memory recall. Despite extensive research, the learning-related role of place cell dynamics in health and disease remains elusive. Using chronic two-photon Ca imaging in hippocampal area CA1 of wild-type and Df(16)A mice, an animal model of 22q11.2 deletion syndrome, one of the most common genetic risk factors for cognitive dysfunction and schizophrenia, we found that goal-oriented learning in wild-type mice was supported by stable spatial maps and robust remapping of place fields toward the goal location. Df(16)A mice showed a significant learning deficit accompanied by reduced spatial map stability and the absence of goal-directed place cell reorganization. These results expand our understanding of the hippocampal ensemble dynamics supporting cognitive flexibility and demonstrate their importance in a model of 22q11.2-associated cognitive dysfunction.
[Mh] Termos MeSH primário: Síndrome de DiGeorge/genética
Síndrome de DiGeorge/fisiopatologia
Modelos Animais de Doenças
Hipocampo/fisiopatologia
Aprendizagem/fisiologia
Células de Lugar/fisiologia
[Mh] Termos MeSH secundário: Animais
Feminino
Metas
Hipocampo/patologia
Seres Humanos
Masculino
Camundongos
Camundongos Endogâmicos C57BL
Camundongos Transgênicos
Células de Lugar/patologia
Distribuição Aleatória
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Em] Mês de entrada:1711
[Cu] Atualização por classe:171102
[Lr] Data última revisão:
171102
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170905
[St] Status:MEDLINE
[do] DOI:10.1038/nn.4634


  9 / 1822 MEDLINE  
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[PMID]:28750581
[Au] Autor:Bassett AS; Lowther C; Merico D; Costain G; Chow EWC; van Amelsvoort T; McDonald-McGinn D; Gur RE; Swillen A; Van den Bree M; Murphy K; Gothelf D; Bearden CE; Eliez S; Kates W; Philip N; Sashi V; Campbell L; Vorstman J; Cubells J; Repetto GM; Simon T; Boot E; Heung T; Evers R; Vingerhoets C; van Duin E; Zackai E; Vergaelen E; Devriendt K; Vermeesch JR; Owen M; Murphy C; Michaelovosky E; Kushan L; Schneider M; Fremont W; Busa T; Hooper S; McCabe K; Duijff S; Isaev K; Pellecchia G; Wei J; Gazzellone MJ; Scherer SW; Emanuel BS; Guo T; Morrow BE; Marshall CR; International 22q11.2DS Brain and Behavior Consortium
[Ad] Endereço:From the Dalglish Family 22q Clinic, Department of Psychiatry, University Health Network, Toronto; the Department of Psychiatry and Toronto General Research Institute, University Health Network, Toronto; the Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, To
[Ti] Título:Rare Genome-Wide Copy Number Variation and Expression of Schizophrenia in 22q11.2 Deletion Syndrome.
[So] Source:Am J Psychiatry;174(11):1054-1063, 2017 Nov 01.
[Is] ISSN:1535-7228
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:OBJECTIVE: Chromosome 22q11.2 deletion syndrome (22q11.2DS) is associated with a more than 20-fold increased risk for developing schizophrenia. The aim of this study was to identify additional genetic factors (i.e., "second hits") that may contribute to schizophrenia expression. METHOD: Through an international consortium, the authors obtained DNA samples from 329 psychiatrically phenotyped subjects with 22q11.2DS. Using a high-resolution microarray platform and established methods to assess copy number variation (CNV), the authors compared the genome-wide burden of rare autosomal CNV, outside of the 22q11.2 deletion region, between two groups: a schizophrenia group and those with no psychotic disorder at age ≥25 years. The authors assessed whether genes overlapped by rare CNVs were overrepresented in functional pathways relevant to schizophrenia. RESULTS: Rare CNVs overlapping one or more protein-coding genes revealed significant between-group differences. For rare exonic duplications, six of 19 gene sets tested were enriched in the schizophrenia group; genes associated with abnormal nervous system phenotypes remained significant in a stepwise logistic regression model and showed significant interactions with 22q11.2 deletion region genes in a connectivity analysis. For rare exonic deletions, the schizophrenia group had, on average, more genes overlapped. The additional rare CNVs implicated known (e.g., GRM7, 15q13.3, 16p12.2) and novel schizophrenia risk genes and loci. CONCLUSIONS: The results suggest that additional rare CNVs overlapping genes outside of the 22q11.2 deletion region contribute to schizophrenia risk in 22q11.2DS, supporting a multigenic hypothesis for schizophrenia. The findings have implications for understanding expression of psychotic illness and herald the importance of whole-genome sequencing to appreciate the overall genomic architecture of schizophrenia.
[Mh] Termos MeSH primário: Transtorno do Espectro Autista/genética
Transtorno Autístico/genética
Transtornos Cromossômicos/genética
Síndrome de DiGeorge/genética
Deficiência Intelectual/genética
Esquizofrenia/genética
[Mh] Termos MeSH secundário: Adulto
Transtorno do Espectro Autista/psicologia
Transtorno Autístico/psicologia
Deleção Cromossômica
Transtornos Cromossômicos/psicologia
Cromossomos Humanos Par 16/genética
Variações do Número de Cópias de DNA
Síndrome de DiGeorge/psicologia
Feminino
Seres Humanos
Deficiência Intelectual/psicologia
Masculino
Meia-Idade
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Em] Mês de entrada:1711
[Cu] Atualização por classe:171107
[Lr] Data última revisão:
171107
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:170729
[St] Status:MEDLINE
[do] DOI:10.1176/appi.ajp.2017.16121417


  10 / 1822 MEDLINE  
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[PMID]:28734657
[Au] Autor:Goldmuntz E; Cassedy A; Mercer-Rosa L; Fogel MA; Paridon SM; Marino BS
[Ad] Endereço:Division of Cardiology, Children's Hospital of Philadelphia, Philadelphia, PA. Electronic address: goldmuntz@email.chop.edu.
[Ti] Título:Exercise Performance and 22q11.2 Deletion Status Affect Quality of Life in Tetralogy of Fallot.
[So] Source:J Pediatr;189:162-168, 2017 Oct.
[Is] ISSN:1097-6833
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:OBJECTIVE: To identify mediators of health status and quality of life (QOL) in children and adolescents aged 8-18 years old following surgical repair for tetralogy of Fallot (TOF), including resource use, exercise performance, and 22q11.2 deletion status. STUDY DESIGN: We performed a corollary study to a cross-sectional analysis of subjects following repair for TOF that completed cardiac magnetic resonance imaging, cardiopulmonary exercise tests, and instruments assessing health status and QOL. General linear models were used to test for mediation. RESULTS: A total of 29 of 151 (19%) patients carried a 22q11.2 deletion. Parents of children with a deletion compared with those without a deletion reported worse physical and psychosocial functioning on the Child Health Questionnaire. The patients with a 22q11.2 deletion and their parents reported lower total and Disease Impact scores compared with the group without a deletion on the Pediatric Cardiac Quality of Life Inventory. Medical care use negatively correlated with measures of health status/QOL. Greater maximum work correlated with better patient health status and QOL, regardless of deletion status. Exercise performance mediated the association between deletion status and parent-reported outcomes (unstandardized effects ranging from 2.4 to 4.2) and patient-reported Disease Impact (0.99; 95% CI 0.02-2.70). CONCLUSION: Children and adolescents following repair for TOF seem to suffer significant challenges to their health status and QOL, which is amplified markedly in the context of the 22q11.2 deletion syndrome, and related to exercise performance.
[Mh] Termos MeSH primário: Síndrome de DiGeorge/fisiopatologia
Exercício/fisiologia
Qualidade de Vida/psicologia
Tetralogia de Fallot/fisiopatologia
[Mh] Termos MeSH secundário: Adolescente
Criança
Estudos Transversais
Síndrome de DiGeorge/complicações
Síndrome de DiGeorge/psicologia
Teste de Esforço
Feminino
Nível de Saúde
Seres Humanos
Masculino
Inquéritos e Questionários
Tetralogia de Fallot/complicações
Tetralogia de Fallot/psicologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171003
[Lr] Data última revisão:
171003
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:170724
[St] Status:MEDLINE



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