Homozygous and Heterozygous Nuclear Lamin A p.R582C Mutation: Different Lipodystrophic Phenotypes in the Same Kindred

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art_MONTENEGRO JR._Homozygous_and_Heterozygous_Nuclear_Lamin_A_pR582C_Mutation_2018.PDF (1.62 MB)
Citações na Scopus
10
Tipo de produção
article
Data de publicação
2018
DOI
Scopus
Web of Science
PubMed
Título da Revista
ISSN da Revista
Título do Volume
Editora
FRONTIERS MEDIA SA
Autores
MONTENEGRO JR., Renan Magalhaes
FERNANDES, Virginia Oliveira
MONTENEGRO, Ana Paula Dias Rangel
KARBAGE, Lia Beatriz de Azevedo Souza
AGUIAR, Lindenberg Barbosa
CARVALHO, Francisco Herlanio Costa
Citação
FRONTIERS IN ENDOCRINOLOGY, v.9, article ID 458, 9p, 2018
Projetos de Pesquisa
Unidades Organizacionais
Fascículo
Resumo
Background: Dunnigan-type familial partial lipodystrophy (FPLD2) is a rare autosomal dominant disease caused by heterozygous mutations in the LMNA gene that results in regional loss of subcutaneous adipose tissue with onset in puberty. However, a generalized lipodystrophy phenotype has also been associated with heterozygous mutations in this gene, demonstrating the noticeable phenotypic heterogeneity of this disease. Methods: We report and describe clinical and metabolic features of four patients from the same family with the p.R582C LMNA mutation, three homozygous and one in the heterozygous state that present with three distinct lipodystrophic phenotypes. Results: Case description: The proband was a 12-year-old girl who developed severe subcutaneous fat atrophy in limbs and abdomen followed by a remarkable dorsocervical fat accumulation in adulthood along with diabetes at age 23. The proband's sister was a phenotypically normal girl who developed hypertriglyceridemia at age 8, progressive features of partial lipodystrophy at age 11, and diabetes at age 22. The proband's mother was first examined at age 32, presenting diabetes and a severe generalized lipodystrophic phenotype; she developed kidney failure at age 41 and died due to diabetic complications. The proband's father was a 50-year-old man with abdominal fat concentration that was initially considered phenotypically normal. Massively parallel sequencing using a platform of genes related to genetic lipodystrophies, followed by Sanger sequencing, revealed the transversion c.1744C>T at exon 11 of the LMNA gene (p.R582C) in the homozygous (mother and daughters) and heterozygous (father) states. Conclusion: We documented three distinct phenotypes of the homozygous and heterozygous p. R582C LMNA mutation in the same kindred, illustrating that FPLD2 linked to mutations in this gene is a disease of great clinical heterogeneity, possibly due to associated environmental or genetic factors.
Palavras-chave
Dunnigan, partial lipodystrophy, generalized lipodystrophy, LMNA, FPLD2, phenotypic heterogen
URI
https://observatorio.fm.usp.br/handle/OPI/28000
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Coleções
Artigos e Materiais de Revistas Científicas - FM/MCM
Artigos e Materiais de Revistas Científicas - HC/ICHC
Artigos e Materiais de Revistas Científicas - LIM/25
Artigos e Materiais de Revistas Científicas - ODS/03