Clinical and molecular characterization of a brazilian cohort of campomelic dysplasia patients, and identification of seven new SOX9 mutations
Autor(a) principal: | |
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Data de Publicação: | 2015 |
Outros Autores: | , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da UFRGS |
Texto Completo: | http://hdl.handle.net/10183/164849 |
Resumo: | Campomelic dysplasia (CD) is an autosomal, dominantly inherited, skeletal abnormality belonging to the subgroup of bent bone dysplasias. In addition to bowed lower limbs, CD typically includes the following: disproportionate short stature, flat face, micrognathia, cleft palate, bell-shaped thorax, and club feet. Up to three quarters of 46,XY individuals may be sex-reversed. Radiological signs include scapular and pubic hypoplasia, narrow iliac wings, spaced ischia, and bowed femora and tibiae. Lethal CD is usually due to heterozygous mutations in SOX9, a major regulator of chondrocytic development. We present a detailed clinical and molecular characterization of nine Brazilian CD patients. Infants were either stillborn (n = 2) or died shortly after birth and presented similar phenotypes. Sex-reversal was observed in one of three chromosomally male patients. Sequencing of SOX9 revealed new heterozygous mutations in seven individuals. Six patients had mutations that resulted in premature transcriptional termination, while one infant had a single-nucleotide substitution at the conserved splice-site acceptor of intron 1. No clear genotype-phenotype correlations were observed. This study highlights the diversity of SOX9 mutations leading to lethal CD, and expands the group of known genetic alterations associated with this skeletal dysplasia. |
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Mattos, Eduardo Preusser deSanseverino, Maria Teresa VieiraMagalhães, Jose Antonio de AzevedoLeite, Júlio César LoguercioFelix, Temis MariaTodeschini, Luis AlbertoCavalcanti, Denise P.Faccini, Lavinia Schuler2017-08-04T02:39:38Z20151415-4757http://hdl.handle.net/10183/164849001021030Campomelic dysplasia (CD) is an autosomal, dominantly inherited, skeletal abnormality belonging to the subgroup of bent bone dysplasias. In addition to bowed lower limbs, CD typically includes the following: disproportionate short stature, flat face, micrognathia, cleft palate, bell-shaped thorax, and club feet. Up to three quarters of 46,XY individuals may be sex-reversed. Radiological signs include scapular and pubic hypoplasia, narrow iliac wings, spaced ischia, and bowed femora and tibiae. Lethal CD is usually due to heterozygous mutations in SOX9, a major regulator of chondrocytic development. We present a detailed clinical and molecular characterization of nine Brazilian CD patients. Infants were either stillborn (n = 2) or died shortly after birth and presented similar phenotypes. Sex-reversal was observed in one of three chromosomally male patients. Sequencing of SOX9 revealed new heterozygous mutations in seven individuals. Six patients had mutations that resulted in premature transcriptional termination, while one infant had a single-nucleotide substitution at the conserved splice-site acceptor of intron 1. No clear genotype-phenotype correlations were observed. This study highlights the diversity of SOX9 mutations leading to lethal CD, and expands the group of known genetic alterations associated with this skeletal dysplasia.application/pdfengGenetics and molecular biology. Ribeirão Preto, SP. Vol. 38, no. 1, (Jan./Mar. 2015), p. 14-20Displasia campomélicaOsteocondrodisplasiasDiagnóstico pré-natalCampomelic dysplasiaSkeletal dysplasiaOsteochondrodysplasiasSOX9Prenatal diagnosisClinical and molecular characterization of a brazilian cohort of campomelic dysplasia patients, and identification of seven new SOX9 mutationsinfo:eu-repo/semantics/articleinfo:eu-repo/semantics/otherinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da UFRGSinstname:Universidade Federal do Rio Grande do Sul (UFRGS)instacron:UFRGSORIGINAL001021030.pdf001021030.pdfTexto completo (inglês)application/pdf1448293http://www.lume.ufrgs.br/bitstream/10183/164849/1/001021030.pdf5658e9a30173282ddc6564092e04348bMD51TEXT001021030.pdf.txt001021030.pdf.txtExtracted Texttext/plain28793http://www.lume.ufrgs.br/bitstream/10183/164849/2/001021030.pdf.txt276b7153a6afcd8801ca9121cac71b38MD52THUMBNAIL001021030.pdf.jpg001021030.pdf.jpgGenerated Thumbnailimage/jpeg1845http://www.lume.ufrgs.br/bitstream/10183/164849/3/001021030.pdf.jpgf6b70d5ce173440cd21e407d1b0068e2MD5310183/1648492023-02-10 05:56:38.661317oai:www.lume.ufrgs.br:10183/164849Repositório de PublicaçõesPUBhttps://lume.ufrgs.br/oai/requestopendoar:2023-02-10T07:56:38Repositório Institucional da UFRGS - Universidade Federal do Rio Grande do Sul (UFRGS)false |
dc.title.pt_BR.fl_str_mv |
Clinical and molecular characterization of a brazilian cohort of campomelic dysplasia patients, and identification of seven new SOX9 mutations |
title |
Clinical and molecular characterization of a brazilian cohort of campomelic dysplasia patients, and identification of seven new SOX9 mutations |
spellingShingle |
Clinical and molecular characterization of a brazilian cohort of campomelic dysplasia patients, and identification of seven new SOX9 mutations Mattos, Eduardo Preusser de Displasia campomélica Osteocondrodisplasias Diagnóstico pré-natal Campomelic dysplasia Skeletal dysplasia Osteochondrodysplasias SOX9 Prenatal diagnosis |
title_short |
Clinical and molecular characterization of a brazilian cohort of campomelic dysplasia patients, and identification of seven new SOX9 mutations |
title_full |
Clinical and molecular characterization of a brazilian cohort of campomelic dysplasia patients, and identification of seven new SOX9 mutations |
title_fullStr |
Clinical and molecular characterization of a brazilian cohort of campomelic dysplasia patients, and identification of seven new SOX9 mutations |
title_full_unstemmed |
Clinical and molecular characterization of a brazilian cohort of campomelic dysplasia patients, and identification of seven new SOX9 mutations |
title_sort |
Clinical and molecular characterization of a brazilian cohort of campomelic dysplasia patients, and identification of seven new SOX9 mutations |
author |
Mattos, Eduardo Preusser de |
author_facet |
Mattos, Eduardo Preusser de Sanseverino, Maria Teresa Vieira Magalhães, Jose Antonio de Azevedo Leite, Júlio César Loguercio Felix, Temis Maria Todeschini, Luis Alberto Cavalcanti, Denise P. Faccini, Lavinia Schuler |
author_role |
author |
author2 |
Sanseverino, Maria Teresa Vieira Magalhães, Jose Antonio de Azevedo Leite, Júlio César Loguercio Felix, Temis Maria Todeschini, Luis Alberto Cavalcanti, Denise P. Faccini, Lavinia Schuler |
author2_role |
author author author author author author author |
dc.contributor.author.fl_str_mv |
Mattos, Eduardo Preusser de Sanseverino, Maria Teresa Vieira Magalhães, Jose Antonio de Azevedo Leite, Júlio César Loguercio Felix, Temis Maria Todeschini, Luis Alberto Cavalcanti, Denise P. Faccini, Lavinia Schuler |
dc.subject.por.fl_str_mv |
Displasia campomélica Osteocondrodisplasias Diagnóstico pré-natal |
topic |
Displasia campomélica Osteocondrodisplasias Diagnóstico pré-natal Campomelic dysplasia Skeletal dysplasia Osteochondrodysplasias SOX9 Prenatal diagnosis |
dc.subject.eng.fl_str_mv |
Campomelic dysplasia Skeletal dysplasia Osteochondrodysplasias SOX9 Prenatal diagnosis |
description |
Campomelic dysplasia (CD) is an autosomal, dominantly inherited, skeletal abnormality belonging to the subgroup of bent bone dysplasias. In addition to bowed lower limbs, CD typically includes the following: disproportionate short stature, flat face, micrognathia, cleft palate, bell-shaped thorax, and club feet. Up to three quarters of 46,XY individuals may be sex-reversed. Radiological signs include scapular and pubic hypoplasia, narrow iliac wings, spaced ischia, and bowed femora and tibiae. Lethal CD is usually due to heterozygous mutations in SOX9, a major regulator of chondrocytic development. We present a detailed clinical and molecular characterization of nine Brazilian CD patients. Infants were either stillborn (n = 2) or died shortly after birth and presented similar phenotypes. Sex-reversal was observed in one of three chromosomally male patients. Sequencing of SOX9 revealed new heterozygous mutations in seven individuals. Six patients had mutations that resulted in premature transcriptional termination, while one infant had a single-nucleotide substitution at the conserved splice-site acceptor of intron 1. No clear genotype-phenotype correlations were observed. This study highlights the diversity of SOX9 mutations leading to lethal CD, and expands the group of known genetic alterations associated with this skeletal dysplasia. |
publishDate |
2015 |
dc.date.issued.fl_str_mv |
2015 |
dc.date.accessioned.fl_str_mv |
2017-08-04T02:39:38Z |
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info:eu-repo/semantics/article info:eu-repo/semantics/other |
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publishedVersion |
dc.identifier.uri.fl_str_mv |
http://hdl.handle.net/10183/164849 |
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1415-4757 |
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001021030 |
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http://hdl.handle.net/10183/164849 |
dc.language.iso.fl_str_mv |
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language |
eng |
dc.relation.ispartof.pt_BR.fl_str_mv |
Genetics and molecular biology. Ribeirão Preto, SP. Vol. 38, no. 1, (Jan./Mar. 2015), p. 14-20 |
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