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Comprehensive cDNA study and quantitative analysis of mutant HADHA and HADHB transcripts in a French cohort of 52 patients with mitochondrial trifunctional protein deficiency
- Source :
- Molecular Genetics and Metabolism. 103:341-348
- Publication Year :
- 2011
- Publisher :
- Elsevier BV, 2011.
-
Abstract
- Background Deficiency of mitochondrial trifunctional protein (MTP) is caused by mutations in the HADHA and HADHB genes, which have been mostly delineated at the genomic DNA level and have not been always elucidated. Aim To identify mutations in a French cohort of 52 MTP deficient patients and the susceptibility of mutations generating premature termination codons (PTCs) to the nonsense mRNA mediated decay (NMD). Methods Mutation screening in fibroblasts was performed at the cDNA level and real-time RT-PCR was used to compare the levels of the different PTC-bearing mRNAs before and after a treatment of fibroblasts by emetine, a translation inhibitor. Results A mutation detection rate of 100% was achieved. A total of 22 novel mutations were identified, including a large-sized genomic deletion in HADHB gene. A high proportion of all identified mutations were non-sense, frameshift and splicing mutations, generating (PTCs), distributed essentially on HADHA coding regions. We could demonstrate that the majority of mutations resulting in PTCs conform to the established rules governing the susceptibility to NMD. Conclusion Our results emphasize the value of cDNA analysis in the characterization of HADHA and HADHB mutations and further strengthen the model of haploinsufficiency as a major pathomechanism in MTP defects.
- Subjects :
- Male
DNA, Complementary
Mitochondrial Diseases
Endocrinology, Diabetes and Metabolism
Molecular Sequence Data
Lipid Metabolism Disorders
Haploinsufficiency
Mitochondrial trifunctional protein deficiency
Mitochondrial trifunctional protein
medicine.disease_cause
Biochemistry
Frameshift mutation
Cohort Studies
Mitochondrial Proteins
Endocrinology
Multienzyme Complexes
Complementary DNA
Genetics
medicine
Humans
Molecular Biology
Gene
Mutation
Base Sequence
biology
Mitochondrial Trifunctional Protein
Reverse Transcriptase Polymerase Chain Reaction
Sequence Analysis, DNA
medicine.disease
Molecular biology
Mitochondrial Trifunctional Protein, beta Subunit
biology.protein
Female
France
Mitochondrial Trifunctional Protein, alpha Subunit
HADHB
Subjects
Details
- ISSN :
- 10967192
- Volume :
- 103
- Database :
- OpenAIRE
- Journal :
- Molecular Genetics and Metabolism
- Accession number :
- edsair.doi.dedup.....4da71f6f994760fa225dcea19bfffb1e