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Title Avaliação das displasias esqueléticas letais e investigação das bases moleculares de um fenótipo inédito utilizando sequenciamento de alto desempenho: Evaluation of a local casuistry of lethal skeletal dysplasias and study of the molecular bases of an novel phenotype using high-performance sequencing
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University/Publisher Universidade Estadual de Campinas
Abstract Abstract: The osteochondrodysplasias (OCD) are genetic diseases that affect the growth and development of the chondro-osseous tissue leading to short stature, and body disproportion in several individuals, and contribute to the infant morbimortality. Around one-third of these conditions are lethal in the perinatal period, being thanatophoric dysplasia (TD) and lethal osteogenesis imperfecta (OI) the most frequent lethal-OCD. Some OCD in this group are extremely rare, present great clinical-radiological variability and used to be etiologically heterogeneous. Epidemiological information regarding the lethal-OCD is limited and outdated. The aim of this study was to perform a descriptive clinical-epidemiological study based on a local series of cases collected over 26 years. In addition, this study aimed to investigate the molecular bases of two fetuses with a novel phenotype by the whole exome sequencing (WES). The clinical data related to birth, prenatal, family, and clinical-radiological and molecular diagnoses were computed in a spreadsheet and analyzed descriptively. DNA samples from the two fetuses with the novel phenotype were submitted to the exome analysis with the trio approach for both families. In the period 1990 - 2016, a total of 131 fetuses with lethal-OCD evaluated and included in the present study. Among the patients born locally, the high prevalence [9.4 (CI = 7.40-11.79) per 10,000 births] found can be attributed to the bias of reference hospital. Prenatal diagnosis of skeletal dysplasia was performed in 80 cases (61.1%), however, this examination is still very imprecise regarding to reach the specific type of OCD. The high parental consanguinity rate (9.2%) found in this series of cases is, at least partially explained, by the origin of the families from the Brazilian Northeast. The most common groups and lethal phenotypes found were: the FGFR3 group [43 (32.8%)] mainly represented by DT-I [36 (83.7%)]; the OI group [33 (25.2%)] with OI-IIA [22 (66.7%)] as the most common; and the collagenopathies type 2 group [17 (13%)], being the achondrogenesis type II (ACG-II) [10 (58.8%)] the most frequent condition. Together these three groups represent 71% of the total patients. The remaining 38 cases (29%) are distributed in nine other groups. Of the total of 131 cases, 75 (57.3%) had molecular investigation, confirming the radiological diagnosis in 63 cases (84%). The analysis of the exome of the two cases with the novel phenotype was inconclusive. In conclusion, the epidemiological evaluation of the present case series shows a high prevalence of lethal OCD, but related to a bias because it is a reference hospital in the region. The main OCD found are DT-I (FGFR3 group), OI-IIA (OI group) and ACG-II (type 2 collagenopathies group). Although most cases of lethal OCD are suspected during pregnancy, prenatal diagnosis is too imprecise to identify the specific type of the OCD. The high rate of consanguinity found in the sample seems to be due to the origins of the families, most coming from the Brazilian…
Subjects/Keywords Osteocondrodisplasias; Doenças do desenvolvimento ósseo; Epidemiologia; Osteochondrodysplasias; Bone development diseases; Epidemiology
Contributors UNIVERSIDADE ESTADUAL DE CAMPINAS (CRUESP); Cavalcanti, Denise Pontes, 1957- (advisor); Universidade Estadual de Campinas. Faculdade de Ciências Médicas (institution); Programa de Pós-Graduação em Ciências Médicas (nameofprogram); Sanseverino, Maria Teresa Vieira (committee member); Vargas, Fernando Regla (committee member); Vieira, Andre Schwambach (committee member); Secolin, Rodrigo (committee member)
Language português
Country of Publication br
Record ID oai:repositorio.unicamp.br:REPOSIP/334713
Repository unicamp
Date Indexed 2020-09-09
Issued Date 2018-01-01 00:00:00
Note [] Orientador: Denise Pontes Cavalcanti; [] Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas; [degreelevel] Doutorado; [degreediscipline] Genetica Medica; [degreename] Doutora em Ciências; [sponsordocumentnumber] 01-P-3368/2017; [sponsor] CAPES;

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…TGF-β Transforming growth factor beta Thr (T) Treonina Trp (W) Triptofano Tyr (Y) Tirosina UBDN The Utah Birth Defect Network UF Unidade federativa UNICAMP Universidade Estadual de Campinas US Ultrassonografia…

…para 10.000 nascimentos e, entre os natimortos, uma prevalncia de 20,0/10.000 (33). O segundo estudo, realizado pelo grupo local de Displasias Esquelticas da Universidade Estadual de Campinas (UNICAMP), foi baseado nos dados do…

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