Phenotypic diversity in patients with lipodystrophy associated with LMNA mutations
Autor(a) principal: | |
---|---|
Data de Publicação: | 2012 |
Outros Autores: | , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da UNIFESP |
Texto Completo: | http://repositorio.unifesp.br/handle/11600/35197 http://dx.doi.org/10.1530/EJE-12-0268 |
Resumo: | Objective: Mutations in LMNA have been linked to diverse disorders called laminopathies, which display heterogeneous phenotypes and include diseases affecting muscles, axonal neurons, progeroid syndromes, and lipodystrophies. Among the lipodystrophies, LMNA mutations have been reported most frequently in patients with familial partial lipodystrophy (FPLD) of the Dunnigan variety; however, phenotypic heterogeneity in the pattern of body fat loss has been observed. in this study, we searched for LMNA mutations in patients with various forms of lipodystrophy.Design and methods: We studied 21 unrelated individuals with lipodystrophy. Subjects underwent a complete clinical evaluation and were classified as typical FPLD (n=12), atypical partial lipodystrophy (n=7), or generalized lipodystrophy (n=2). Molecular analysis of LMNA gene, analysis of body fat by dual-energy X-ray absorptiometry, and biochemical measurements were performed.Results: All patients with typical FPLD were found to carry LMNA mutations: seven patients harbored the heterozygous p. R482W (c.1444C>T), two patients harbored the p.R482Q (c.1445G>A), and two individuals harbored the novel heterozygous variant p.N466D (c.1396A>G), all in exon 8. Also, a homozygous p.R584H (c.1751 G>A) mutation in exon 11 was found. Among patients with atypical partial lipodystrophy, two of them were found to have LMNA mutations: a novel heterozygous p.R582C variation (c.1744 C>T) in exon 11 and a heterozygous substitution p.R349W (c.1045COT) in exon 6. Among patients with generalized lipodystrophy, only one harbored LMNA mutation, a heterozygous p.T10I (c.29C>T) in exon 1.Conclusions: We have identified LMNA mutations in phenotypically diverse lipodystrophies. Also, our study broadens the spectrum of LMNA mutations in lipodystrophy. |
id |
UFSP_f4653ccca7ca4866e6c4ffcd922d12d2 |
---|---|
oai_identifier_str |
oai:repositorio.unifesp.br:11600/35197 |
network_acronym_str |
UFSP |
network_name_str |
Repositório Institucional da UNIFESP |
repository_id_str |
3465 |
spelling |
Mory, Patricia B. [UNIFESP]Crispim, FelipeFreire, Maria Beatriz S.Salles, Joao Eduardo N.Valerio, Cynthia M.Godoy-Matos, Amelio F.Dib, Sergio A. [UNIFESP]Moises, Regina S. [UNIFESP]Universidade Federal de São Paulo (UNIFESP)Fac Med JundiaiFac Ciencias MedInst Estadual Diabet & Endocrinol2016-01-24T14:27:36Z2016-01-24T14:27:36Z2012-09-01European Journal of Endocrinology. Bristol: Bioscientifica Ltd, v. 167, n. 3, p. 423-431, 2012.0804-4643http://repositorio.unifesp.br/handle/11600/35197http://dx.doi.org/10.1530/EJE-12-026810.1530/EJE-12-0268WOS:000308459200016Objective: Mutations in LMNA have been linked to diverse disorders called laminopathies, which display heterogeneous phenotypes and include diseases affecting muscles, axonal neurons, progeroid syndromes, and lipodystrophies. Among the lipodystrophies, LMNA mutations have been reported most frequently in patients with familial partial lipodystrophy (FPLD) of the Dunnigan variety; however, phenotypic heterogeneity in the pattern of body fat loss has been observed. in this study, we searched for LMNA mutations in patients with various forms of lipodystrophy.Design and methods: We studied 21 unrelated individuals with lipodystrophy. Subjects underwent a complete clinical evaluation and were classified as typical FPLD (n=12), atypical partial lipodystrophy (n=7), or generalized lipodystrophy (n=2). Molecular analysis of LMNA gene, analysis of body fat by dual-energy X-ray absorptiometry, and biochemical measurements were performed.Results: All patients with typical FPLD were found to carry LMNA mutations: seven patients harbored the heterozygous p. R482W (c.1444C>T), two patients harbored the p.R482Q (c.1445G>A), and two individuals harbored the novel heterozygous variant p.N466D (c.1396A>G), all in exon 8. Also, a homozygous p.R584H (c.1751 G>A) mutation in exon 11 was found. Among patients with atypical partial lipodystrophy, two of them were found to have LMNA mutations: a novel heterozygous p.R582C variation (c.1744 C>T) in exon 11 and a heterozygous substitution p.R349W (c.1045COT) in exon 6. Among patients with generalized lipodystrophy, only one harbored LMNA mutation, a heterozygous p.T10I (c.29C>T) in exon 1.Conclusions: We have identified LMNA mutations in phenotypically diverse lipodystrophies. Also, our study broadens the spectrum of LMNA mutations in lipodystrophy.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Universidade Federal de São Paulo, Paulista Sch Med, Div Endocrinol, BR-04039032 São Paulo, BrazilFac Med Jundiai, Jundiai, SP, BrazilFac Ciencias Med, São Paulo, BrazilInst Estadual Diabet & Endocrinol, Rio de Janeiro, BrazilUniversidade Federal de São Paulo, Paulista Sch Med, Div Endocrinol, BR-04039032 São Paulo, BrazilFAPESP: 07/59297-1Web of Science423-431engBioscientifica LtdEuropean Journal of EndocrinologyPhenotypic diversity in patients with lipodystrophy associated with LMNA mutationsinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleinfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da UNIFESPinstname:Universidade Federal de São Paulo (UNIFESP)instacron:UNIFESP11600/351972022-11-04 15:20:28.298metadata only accessoai:repositorio.unifesp.br:11600/35197Repositório InstitucionalPUBhttp://www.repositorio.unifesp.br/oai/requestopendoar:34652022-11-04T18:20:28Repositório Institucional da UNIFESP - Universidade Federal de São Paulo (UNIFESP)false |
dc.title.en.fl_str_mv |
Phenotypic diversity in patients with lipodystrophy associated with LMNA mutations |
title |
Phenotypic diversity in patients with lipodystrophy associated with LMNA mutations |
spellingShingle |
Phenotypic diversity in patients with lipodystrophy associated with LMNA mutations Mory, Patricia B. [UNIFESP] |
title_short |
Phenotypic diversity in patients with lipodystrophy associated with LMNA mutations |
title_full |
Phenotypic diversity in patients with lipodystrophy associated with LMNA mutations |
title_fullStr |
Phenotypic diversity in patients with lipodystrophy associated with LMNA mutations |
title_full_unstemmed |
Phenotypic diversity in patients with lipodystrophy associated with LMNA mutations |
title_sort |
Phenotypic diversity in patients with lipodystrophy associated with LMNA mutations |
author |
Mory, Patricia B. [UNIFESP] |
author_facet |
Mory, Patricia B. [UNIFESP] Crispim, Felipe Freire, Maria Beatriz S. Salles, Joao Eduardo N. Valerio, Cynthia M. Godoy-Matos, Amelio F. Dib, Sergio A. [UNIFESP] Moises, Regina S. [UNIFESP] |
author_role |
author |
author2 |
Crispim, Felipe Freire, Maria Beatriz S. Salles, Joao Eduardo N. Valerio, Cynthia M. Godoy-Matos, Amelio F. Dib, Sergio A. [UNIFESP] Moises, Regina S. [UNIFESP] |
author2_role |
author author author author author author author |
dc.contributor.institution.none.fl_str_mv |
Universidade Federal de São Paulo (UNIFESP) Fac Med Jundiai Fac Ciencias Med Inst Estadual Diabet & Endocrinol |
dc.contributor.author.fl_str_mv |
Mory, Patricia B. [UNIFESP] Crispim, Felipe Freire, Maria Beatriz S. Salles, Joao Eduardo N. Valerio, Cynthia M. Godoy-Matos, Amelio F. Dib, Sergio A. [UNIFESP] Moises, Regina S. [UNIFESP] |
description |
Objective: Mutations in LMNA have been linked to diverse disorders called laminopathies, which display heterogeneous phenotypes and include diseases affecting muscles, axonal neurons, progeroid syndromes, and lipodystrophies. Among the lipodystrophies, LMNA mutations have been reported most frequently in patients with familial partial lipodystrophy (FPLD) of the Dunnigan variety; however, phenotypic heterogeneity in the pattern of body fat loss has been observed. in this study, we searched for LMNA mutations in patients with various forms of lipodystrophy.Design and methods: We studied 21 unrelated individuals with lipodystrophy. Subjects underwent a complete clinical evaluation and were classified as typical FPLD (n=12), atypical partial lipodystrophy (n=7), or generalized lipodystrophy (n=2). Molecular analysis of LMNA gene, analysis of body fat by dual-energy X-ray absorptiometry, and biochemical measurements were performed.Results: All patients with typical FPLD were found to carry LMNA mutations: seven patients harbored the heterozygous p. R482W (c.1444C>T), two patients harbored the p.R482Q (c.1445G>A), and two individuals harbored the novel heterozygous variant p.N466D (c.1396A>G), all in exon 8. Also, a homozygous p.R584H (c.1751 G>A) mutation in exon 11 was found. Among patients with atypical partial lipodystrophy, two of them were found to have LMNA mutations: a novel heterozygous p.R582C variation (c.1744 C>T) in exon 11 and a heterozygous substitution p.R349W (c.1045COT) in exon 6. Among patients with generalized lipodystrophy, only one harbored LMNA mutation, a heterozygous p.T10I (c.29C>T) in exon 1.Conclusions: We have identified LMNA mutations in phenotypically diverse lipodystrophies. Also, our study broadens the spectrum of LMNA mutations in lipodystrophy. |
publishDate |
2012 |
dc.date.issued.fl_str_mv |
2012-09-01 |
dc.date.accessioned.fl_str_mv |
2016-01-24T14:27:36Z |
dc.date.available.fl_str_mv |
2016-01-24T14:27:36Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.citation.fl_str_mv |
European Journal of Endocrinology. Bristol: Bioscientifica Ltd, v. 167, n. 3, p. 423-431, 2012. |
dc.identifier.uri.fl_str_mv |
http://repositorio.unifesp.br/handle/11600/35197 http://dx.doi.org/10.1530/EJE-12-0268 |
dc.identifier.issn.none.fl_str_mv |
0804-4643 |
dc.identifier.doi.none.fl_str_mv |
10.1530/EJE-12-0268 |
dc.identifier.wos.none.fl_str_mv |
WOS:000308459200016 |
identifier_str_mv |
European Journal of Endocrinology. Bristol: Bioscientifica Ltd, v. 167, n. 3, p. 423-431, 2012. 0804-4643 10.1530/EJE-12-0268 WOS:000308459200016 |
url |
http://repositorio.unifesp.br/handle/11600/35197 http://dx.doi.org/10.1530/EJE-12-0268 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.ispartof.none.fl_str_mv |
European Journal of Endocrinology |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
423-431 |
dc.publisher.none.fl_str_mv |
Bioscientifica Ltd |
publisher.none.fl_str_mv |
Bioscientifica Ltd |
dc.source.none.fl_str_mv |
reponame:Repositório Institucional da UNIFESP instname:Universidade Federal de São Paulo (UNIFESP) instacron:UNIFESP |
instname_str |
Universidade Federal de São Paulo (UNIFESP) |
instacron_str |
UNIFESP |
institution |
UNIFESP |
reponame_str |
Repositório Institucional da UNIFESP |
collection |
Repositório Institucional da UNIFESP |
repository.name.fl_str_mv |
Repositório Institucional da UNIFESP - Universidade Federal de São Paulo (UNIFESP) |
repository.mail.fl_str_mv |
|
_version_ |
1802764185408372736 |