Author | Itzkovitz, Brandon | |
Author | Jiralerspong, Sarn | |
Author | Nimmo, Graeme | |
Author | Loscalzo, Melissa | |
Author | Horovitz, Dafne Dain Gandelman | |
Author | Snowden, Ann | |
Author | Moser, Ann | |
Author | Steinberg, Steve | |
Author | Braverman, Nancy | |
Access date | 2014-12-22T17:47:57Z | |
Available date | 2014-12-22T17:47:57Z | |
Document date | 2012 | |
Citation | ITZKOVITZ, Brandon et al. Functional characterization of novel mutations inGNPAT andAGPS, causing rhizomelic chondrodysplasia punctata (RCDP) types 2 and 3. Human Mutation, New York, v. 33, n. 1, p. 189-197, 2012. | pt_BR |
ISSN | 1059-7794 | |
URI | https://www.arca.fiocruz.br/handle/icict/9283 | |
Language | eng | pt_BR |
Publisher | Wiley-Liss | pt_BR |
Rights | restricted access | pt_BR |
Title | Functional characterization of novel mutations inGNPAT andAGPS, causing rhizomelic chondrodysplasia punctata (RCDP) types 2 and 3 | pt_BR |
Type | Article | pt_BR |
DOI | 10.1002/humu.21623 | pt_BR |
Abstract | Rhizomelic chondrodysplasia punctata
(RCDP) is a disorder of peroxisome metabolism result-ing from a deficiency of plasmalogens, a specialized class
of membrane phospholipids. Classically, patients have a
skeletal dysplasia and profound mental retardation, al-though milder phenotypes are increasingly being iden-tified. It is commonly caused by defects in the peroxi-some transporter, PEX7 (RCDP1), and less frequently
due to defects in the peroxisomal enzymes required to initi-ate plasmalogen synthesis, GNPAT (RCDP2) and AGPS
(RCDP3). PEX7 transports AGPS into the peroxisome,
where AGPS and GNPAT partner on the luminal mem-brane surface. The presence of AGPS is thought to be
required for GNPAT activity. We present six additional
probands with RCDP2 and RCDP3, and the novel muta-tions identified in them. Using cell lines from these and
previously reported patients, we compared the amounts
of both AGPS and GNPAT proteins present for the first
time. We used protein modeling to predict the structural
consequences ofAGPSmutations and transcript analysis
to predict consequences ofGNPATmutations, and show
that milder RCDP phenotypes are likely to be associated
with residual protein function. In addition, we propose
that full GNPAT activity depends not only on the pres-ence of AGPS, but also on the integrity of substrate chan-neling from GNPAT to AGPS. | pt_BR |
Affilliation | Montreal Children’s Hospital Research Institute. Montreal, Quebec, Canada. | pt_BR |
Affilliation | Montreal Children’s Hospital Research Institute. Montreal, Quebec, Canada. | pt_BR |
Affilliation | Montreal Children’s Hospital Research Institute. Montreal, Quebec, Canada. | pt_BR |
Affilliation | University of South. Department of Pediatrics. Division of Genetics. Tampa, Florida. | pt_BR |
Affilliation | Fundação Oswlado Cruz. Instituto Fernandes Figueira. Centro de Genética Médica. Rio de Janeiro, RJ, Brasil. | pt_BR |
Affilliation | Kennedy Krieger Institute. Department of Neurogenetics. Baltimore, Maryland. | pt_BR |
Affilliation | Kennedy Krieger Institute. Department of Neurogenetics. Baltimore, Maryland. | pt_BR |
Affilliation | Kennedy Krieger Institute. Department of Neurogenetics. Baltimore, Maryland / Johns Hopkins University. Department of Neurology. Baltimore, Maryland. | pt_BR |
Affilliation | Montreal Children’s Hospital Research Institute. Montreal, Quebec, Canada / McGill University. Department of Human Genetics and Pediatrics. Montreal, Quebec, Canada. | pt_BR |
Subject | Peroxisome Disease | pt_BR |
Subject | RCDP | pt_BR |
Subject | Plasmalogen | pt_BR |
Subject | AGPS | pt_BR |
Subject | GNPAT | pt_BR |
DeCS | Doença | pt_BR |
DeCS | Plasmalogênios | pt_BR |