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HADHA and HADHB gene associated phenotypes - Identification of rare variants in a patient cohort by Next Generation Sequencing
- Publication Year :
- 2019
-
Abstract
- The heterooctameric mitochondrial trifunctional protein (MTP), composed of four α- and β-subunits harbours three enzymes that each perform a different function in mitochondrial fatty acid β-oxidation. Pathogenic variants in the MTP genes (HADHA and HADHB) cause MTP deficiency, a rare autosomal recessive metabolic disorder characterized by phenotypic heterogeneity ranging from severe, early-onset, cardiac disease to milder, later-onset, myopathy and neuropathy. Since metabolic myopathies and neuropathies are a group of rare genetic disorders and their associated muscle symptoms may be subtle, the diagnosis is often delayed. Here we evaluated data of 161 patients with myopathy and 242 patients with neuropathy via next generation sequencing (NGS) and report the diagnostic yield in three patients of this cohort by the detection of disease-causing variants in the HADHA or HADHB gene. The mitigated phenotypes of this treatable disease were missed by the newborn screening, highlighting the importance of phenotype-based NGS analysis in patients with rare and clinically very variable disorders such as MTP deficiency.
- Subjects :
- Male
Adolescent
Medizin
Metabolic myopathy
Mitochondrial trifunctional protein
Disease
Biology
Bioinformatics
Lipid Metabolism, Inborn Errors
Rhabdomyolysis
Cohort Studies
03 medical and health sciences
medicine
Humans
Myopathy
Child
Molecular Biology
030304 developmental biology
0303 health sciences
Newborn screening
030306 microbiology
Genetic heterogeneity
Mitochondrial Trifunctional Protein
Metabolic disorder
High-Throughput Nucleotide Sequencing
Infant
Mitochondrial Myopathies
Cell Biology
Syndrome
medicine.disease
Phenotype
Child, Preschool
Mitochondrial Trifunctional Protein, beta Subunit
Mutation
biology.protein
Female
Mitochondrial Trifunctional Protein, alpha Subunit
medicine.symptom
Nervous System Diseases
Cardiomyopathies
HADHB
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Accession number :
- edsair.doi.dedup.....450321f28c5d33747bbf52715be98ff8