共 21 条
Functional Effects of Different Medium-Chain Acyl-CoA Dehydrogenase Genotypes and Identification of Asymptomatic Variants
被引:19
作者:
Sturm, Marga
[1
]
Herebian, Diran
[1
]
Mueller, Martina
[1
]
Laryea, Maurice D.
[1
]
Spiekerkoetter, Ute
[1
]
机构:
[1] Univ Childrens Hosp, Dept Gen Pediat, Dusseldorf, Germany
来源:
PLOS ONE
|
2012年
/
7卷
/
09期
关键词:
NEW-YORK-STATE;
MCAD DEFICIENCY;
MUTATION;
POPULATION;
CHALLENGES;
PHENOTYPE;
DEFECTS;
GENE;
D O I:
10.1371/journal.pone.0045110
中图分类号:
O [数理科学和化学];
P [天文学、地球科学];
Q [生物科学];
N [自然科学总论];
学科分类号:
07 ;
0710 ;
09 ;
摘要:
Medium-chain acyl-CoA dehydrogenase (MCAD) deficiency (OMIM 201450) is the most common inherited disorder of fatty acid metabolism presenting with hypoglycaemia, hepatopathy and Reye-like symptoms during catabolism. In the past, the majority of patients carried the prevalent c.985A>G mutation in the ACADM gene. Since the introduction of newborn screening many other mutations with unknown clinical relevance have been identified in asymptomatic newborns. In order to identify functional effects of these mutant genotypes we correlated residual MCAD (OMIM 607008) activities as measured by octanoyl-CoA oxidation in lymphocytes with both genotype and relevant medical reports in 65 newborns harbouring mutant alleles. We identified true disease-causing mutations with residual activities of 0 to 20%. In individuals carrying the c.199T>C or c.127G>A mutation on one allele, residual activities were much higher and in the range of heterozygotes (31%-60%). Therefore, both mutations cannot clearly be associated with a clinical phenotype. This demonstrates a correlation between the octanoyl-CoA oxidation rate in lymphocytes and the clinical outcome. With newborn screening, the natural course of disease is difficult to assess. The octanoyl-CoA oxidation rate, therefore, allows a risk assessment at birth and the identification of new ACADM genotypes associated with asymptomatic disease variants.
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页数:7
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