Clinical and molecular characterization of a Brazilian cohort of campomelic dysplasia patients, and identification of seven new SOX9 mutations

Detalhes bibliográficos
Autor(a) principal: Mattos,Eduardo P.
Data de Publicação: 2015
Outros Autores: Sanseverino,Maria Teresa V., Magalhães,José Antônio A., Leite,Júlio César L., Félix,Temis Maria, Todeschini,Luiz Alberto, Cavalcanti,Denise P., Schüler-Faccini,Lavinia
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Genetics and Molecular Biology
Texto Completo: http://old.scielo.br/scielo.php?script=sci_arttext&pid=S1415-47572015000100014
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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spelling Clinical and molecular characterization of a Brazilian cohort of campomelic dysplasia patients, and identification of seven new SOX9 mutationscampomelic dysplasiaskeletal dysplasiaosteochondrodysplasiasSOX9prenatal diagnosisCampomelic 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.Sociedade Brasileira de Genética2015-03-01info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersiontext/htmlhttp://old.scielo.br/scielo.php?script=sci_arttext&pid=S1415-47572015000100014Genetics and Molecular Biology v.38 n.1 2015reponame:Genetics and Molecular Biologyinstname:Sociedade Brasileira de Genética (SBG)instacron:SBG10.1590/S1415-475738120140147info:eu-repo/semantics/openAccessMattos,Eduardo P.Sanseverino,Maria Teresa V.Magalhães,José Antônio A.Leite,Júlio César L.Félix,Temis MariaTodeschini,Luiz AlbertoCavalcanti,Denise P.Schüler-Faccini,Laviniaeng2015-04-22T00:00:00Zoai:scielo:S1415-47572015000100014Revistahttp://www.gmb.org.br/ONGhttps://old.scielo.br/oai/scielo-oai.php||editor@gmb.org.br1678-46851415-4757opendoar:2015-04-22T00:00Genetics and Molecular Biology - Sociedade Brasileira de Genética (SBG)false
dc.title.none.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 P.
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 P.
author_facet Mattos,Eduardo P.
Sanseverino,Maria Teresa V.
Magalhães,José Antônio A.
Leite,Júlio César L.
Félix,Temis Maria
Todeschini,Luiz Alberto
Cavalcanti,Denise P.
Schüler-Faccini,Lavinia
author_role author
author2 Sanseverino,Maria Teresa V.
Magalhães,José Antônio A.
Leite,Júlio César L.
Félix,Temis Maria
Todeschini,Luiz Alberto
Cavalcanti,Denise P.
Schüler-Faccini,Lavinia
author2_role author
author
author
author
author
author
author
dc.contributor.author.fl_str_mv Mattos,Eduardo P.
Sanseverino,Maria Teresa V.
Magalhães,José Antônio A.
Leite,Júlio César L.
Félix,Temis Maria
Todeschini,Luiz Alberto
Cavalcanti,Denise P.
Schüler-Faccini,Lavinia
dc.subject.por.fl_str_mv campomelic dysplasia
skeletal dysplasia
osteochondrodysplasias
SOX9
prenatal diagnosis
topic 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.none.fl_str_mv 2015-03-01
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dc.relation.none.fl_str_mv 10.1590/S1415-475738120140147
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dc.publisher.none.fl_str_mv Sociedade Brasileira de Genética
publisher.none.fl_str_mv Sociedade Brasileira de Genética
dc.source.none.fl_str_mv Genetics and Molecular Biology v.38 n.1 2015
reponame:Genetics and Molecular Biology
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reponame_str Genetics and Molecular Biology
collection Genetics and Molecular Biology
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