Author | Andrade, Raissa Coelho | |
Author | Nevado, Julián | |
Author | Lima, Maria Angélica de Faria Domingues de | |
Author | Salles, Tania Regina Dias Saad | |
Author | Moraes, Lucia | |
Author | Chimelli, Leila | |
Author | Lapunzina, Pablo | |
Author | Vargas, Fernando Regla | |
Access date | 2015-05-15T13:16:39Z | |
Available date | 2015-05-15T13:16:39Z | |
Document date | 2014 | pt_BR |
Citation | ANDRADE, Raissa Coelho et al. Segmental Uniparental Isodisomy of Chromosome 6 Causing Transient Diabetes Mellitus and Merosin-Deficient Congenital Muscular Dystrophy. American Journal of Medical Genetics Part A, v.164,n.11, p.2908–2913, Nov. 2014. | pt_BR |
ISSN | 1552-4833 | pt_BR |
URI | https://www.arca.fiocruz.br/handle/icict/10312 | |
Language | eng | pt_BR |
Publisher | Wiley Periodicals, Inc. | pt_BR |
Rights | open access | pt_BR |
Subject in Portuguese | Dissomia Uniparental | pt_BR |
Title | Segmental Uniparental Isodisomy of Chromosome 6 Causing Transient Diabetes Mellitus and Merosin-Deficient Congenital Muscular Dystrophy | pt_BR |
Type | Article | pt_BR |
DOI | http://dx.doi.org/10.1002/ajmg.a.36716 | pt_BR |
Abstract | Segmental uniparental isodisomy (iUPD) is a rare genetic event
that may cause aberrant expression of imprinted genes, and
reduction to homozygosity of a recessive mutation. Transient
neonatal diabetes mellitus (TNDM) is typically caused by imprinting
aberrations in chromosome 6q24 TNDMdifferentiallymethylated
region (DMR). Approximately, 15.12Mb upstream
in 6q22-q23 is located LAMA2, the gene responsible of merosindeficient
congenital muscular dystrophy type 1A (MDC1A).We
investigated a patient diagnosed both with TNDMand MDC1A,
born from a twin dichorionic discordant pregnancy. Parents are
first-degree cousins. Methylation sensitive-PCR of the imprinted
6q24 TNDM CpG island showed only the non-methylated (paternal)
allele. Microsatellite markers and SNP array profiling
disclosed normal biparental inheritance at 6p and a segmental
paternal iUPD, between 6q22.33 and 6q27. Sequencing of
LAMA2 exons showed a homozygous frameshift mutation,
c.7490_7493dupAAGA, which predicts p.Asp2498GlufsX4, in
exon 54. Her father, but not her mother, was a carrier of the
mutation. While segmental paternal iUPD6 causing TNDM was
reported twice, there are no previous reports of MDC1A caused
by this event. This is a child with two genetic disorders, yet
neither is caused by the parental consanguinity, which reinforces
the importance of considering different etiological mechanisms
in the genetic clinic. | pt_BR |
Affilliation | Instituto Nacional de Câncer. Divisão de Genética. Rio de Janeiro, RJ, Brasil. | pt_BR |
Affilliation | Universidad Autónoma de Madrid. INGEMM, Instituto de Genética Médica y Molecular, IdiPAZ-CIBERER. Madrid, Spain. | pt_BR |
Affilliation | Universidade Federal do Estado do Rio de Janeiro. Departamento de Genética e Biologia Molecular. Rio de Janeiro, RJ, Brasil / Universidade UnigranRio. Programa de Internato em Genética. Rio de Janeiro, RJ, Brasil. | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Instituto Fernandes Figueira. Serviço Neuropediátrico. Rio de Janeiro, RJ, Brasil. | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Instituto Fernandes Figueira. Centro de Genética Médica. Rio de Janeiro, RJ, Brasil. | pt_BR |
Affilliation | Universidade Federal do Rio de Janeiro. Escola de Medicina. Departamento de Patologia. Rio de Janeiro, RJ, Brasil. | pt_BR |
Affilliation | Universidad Autónoma de Madrid. INGEMM, Instituto de Genética Médica y Molecular, IdiPAZ-CIBERER. Madrid, Spain. | pt_BR |
Affilliation | Instituto Nacional de Câncer. Divisão de Genética. Rio de Janeiro, RJ, Brasil / Universidade Federal do Estado do Rio de Janeiro. Departamento de Genética e Biologia Molecular. Rio de Janeiro, RJ, Brasil / Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Epidemiologia de Malformações Congênitas. Rio de Janeiro, RJ, Brasil. | pt_BR |
Subject | LAMA2 | pt_BR |
Subject | MDCIA | pt_BR |
Subject | TNDM | pt_BR |
Subject | 6Q24 segmental uniparental disomy | pt_BR |
DeCS | Dissomia Uniparental | pt_BR |