Abstract:
:The mitochondrial 13513G>A (D393N) mutation in the ND5 subunit of the respiratory chain complex I was initially described in association with MELAS syndrome. Recent observations have linked this mutation to Leigh disease. We screened for the 13513G>A mutation in a cohort of 265 patients with Leigh and Leigh-like disease. The mutation was found in a total of 5 patients. An additional patient who had clinical presentation consistent with a Leigh-like phenotype but with a normal brain MRI was added to the cohort. None of an additional 88 patients meeting MELAS disease criteria, nor 56 patients with respiratory chain deficiency screened for the 13513G>A were found positive for the mutation. The most frequent clinical manifestations in our patients were hypotonia, ocular and cerebellar involvement. Low mutation heteroplasmy in the range of 20-40% was observed in all 6 patients. This observation is consistent with the previously reported low heteroplasmy of this mutation in some patients with the 13513G>A mutation and complex I deficiency. However, normal complex I activity was observed in two patients in our cohort. As most patients with Leigh-like disease and the 13513G>A mutation have been described with complex I deficiency, this report adds to the previously reported subset of patients with normal respiratory complex function. We conclude that in any patient with Leigh or Leigh-like disease, testing for the 13513G>A mutation is clinically relevant and low mutant loads in blood or muscle may be considered pathogenic, in the presence of normal respiratory chain enzyme activities.
journal_name
Mol Genet Metabjournal_title
Molecular genetics and metabolismauthors
Brautbar A,Wang J,Abdenur JE,Chang RC,Thomas JA,Grebe TA,Lim C,Weng SW,Graham BH,Wong LJdoi
10.1016/j.ymgme.2008.04.004subject
Has Abstractpub_date
2008-08-01 00:00:00pages
485-90issue
4eissn
1096-7192issn
1096-7206pii
S1096-7192(08)00114-5journal_volume
94pub_type
杂志文章abstract:UNLABELLED:The phenotype of attenuated mucopolysaccharidosis type II (MPS II), also called Hunter syndrome, has not been previously studied in systematic manner. In contrast to the "severe" phenotype, the "attenuated" phenotype does not present with behavioral or cognitive impairment; however, the presence of mild beha...
journal_title:Molecular genetics and metabolism
pub_type: 临床试验,杂志文章,多中心研究
doi:10.1016/j.ymgme.2014.12.299
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abstract::BH(4) administration results in the reduction of blood phenylalanine level in patients with tetrahydrobiopterin (BH(4))-responsive phenylalanine hydroxylase (PAH) deficiency. The mechanism underlying BH(4) response remains unknown. Here, we studied the effects of BH(4) and phenylalanine on in vivo PAH activity of norm...
journal_title:Molecular genetics and metabolism
pub_type: 杂志文章
doi:10.1016/j.ymgme.2007.07.013
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journal_title:Molecular genetics and metabolism
pub_type: 杂志文章
doi:10.1016/j.ymgme.2016.12.010
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pub_type: 杂志文章
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journal_title:Molecular genetics and metabolism
pub_type: 传,历史文章,杂志文章,评审
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journal_title:Molecular genetics and metabolism
pub_type: 杂志文章
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pub_type: 杂志文章,随机对照试验
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journal_title:Molecular genetics and metabolism
pub_type: 杂志文章
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journal_title:Molecular genetics and metabolism
pub_type: 杂志文章
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journal_title:Molecular genetics and metabolism
pub_type: 杂志文章
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abstract::Mucopolysaccharidoses (MPS) are caused by deficiency of lysosomal enzyme activities needed to degrade glycosaminoglycans (GAGs), which are long unbranched polysaccharides consisting of repeating disaccharides. GAGs include: chondroitin sulfate (CS), dermatan sulfate (DS), heparan sulfate (HS), keratan sulfate (KS), an...
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pub_type: 杂志文章,评审
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更新日期:2013-09-01 00:00:00
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journal_title:Molecular genetics and metabolism
pub_type: 杂志文章
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更新日期:2010-10-01 00:00:00
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journal_title:Molecular genetics and metabolism
pub_type: 杂志文章
doi:10.1016/j.ymgme.2015.04.005
更新日期:2015-06-01 00:00:00
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journal_title:Molecular genetics and metabolism
pub_type: 杂志文章
doi:10.1016/j.ymgme.2010.06.006
更新日期:2010-10-01 00:00:00
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journal_title:Molecular genetics and metabolism
pub_type: 杂志文章
doi:10.1016/j.ymgme.2010.04.007
更新日期:2010-08-01 00:00:00
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journal_title:Molecular genetics and metabolism
pub_type: 杂志文章
doi:10.1016/j.ymgme.2014.07.014
更新日期:2014-09-01 00:00:00
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journal_title:Molecular genetics and metabolism
pub_type: 杂志文章,多中心研究
doi:10.1016/j.ymgme.2010.07.006
更新日期:2010-10-01 00:00:00
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pub_type: 杂志文章
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journal_title:Molecular genetics and metabolism
pub_type: 杂志文章
doi:10.1006/mgme.1999.2958
更新日期:2000-02-01 00:00:00
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journal_title:Molecular genetics and metabolism
pub_type: 临床试验,杂志文章
doi:10.1016/j.ymgme.2014.02.007
更新日期:2014-05-01 00:00:00
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journal_title:Molecular genetics and metabolism
pub_type: 杂志文章
doi:10.1016/j.ymgme.2013.02.010
更新日期:2013-05-01 00:00:00
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journal_title:Molecular genetics and metabolism
pub_type: 杂志文章
doi:10.1016/j.ymgme.2003.08.020
更新日期:2003-11-01 00:00:00
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pub_type: 杂志文章
doi:10.1016/j.ymgme.2011.03.001
更新日期:2011-06-01 00:00:00
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journal_title:Molecular genetics and metabolism
pub_type: 杂志文章
doi:10.1006/mgme.1998.2706
更新日期:1998-06-01 00:00:00
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pub_type: 杂志文章
doi:10.1016/j.ymgme.2010.09.012
更新日期:2010-12-01 00:00:00
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journal_title:Molecular genetics and metabolism
pub_type: 杂志文章
doi:10.1016/j.ymgme.2008.03.013
更新日期:2008-07-01 00:00:00
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journal_title:Molecular genetics and metabolism
pub_type: 杂志文章
doi:10.1016/j.ymgme.2010.04.001
更新日期:2010-07-01 00:00:00
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pub_type: 杂志文章
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更新日期:2012-03-01 00:00:00
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journal_title:Molecular genetics and metabolism
pub_type: 杂志文章,评审
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更新日期:2000-07-01 00:00:00