HADHA and HADHB gene associated phenotypes - Identification of rare variants in a patient cohort by Next Generation Sequencing.
Adolescent
Cardiomyopathies
/ genetics
Child
Child, Preschool
Cohort Studies
Female
High-Throughput Nucleotide Sequencing
/ methods
Humans
Infant
Lipid Metabolism, Inborn Errors
/ genetics
Male
Mitochondrial Myopathies
/ genetics
Mitochondrial Trifunctional Protein
/ deficiency
Mitochondrial Trifunctional Protein, alpha Subunit
/ genetics
Mitochondrial Trifunctional Protein, beta Subunit
/ genetics
Mutation
/ genetics
Nervous System Diseases
/ genetics
Phenotype
Rhabdomyolysis
/ genetics
Syndrome
HADHA
HADHB
Metabolic myopathy
Mitochondrial trifunctional protein
Neuropathy
Next generation sequencing
Journal
Molecular and cellular probes
ISSN: 1096-1194
Titre abrégé: Mol Cell Probes
Pays: England
ID NLM: 8709751
Informations de publication
Date de publication:
04 2019
04 2019
Historique:
received:
13
12
2018
revised:
17
01
2019
accepted:
20
01
2019
pubmed:
27
1
2019
medline:
7
5
2019
entrez:
26
1
2019
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 30682426
pii: S0890-8508(18)30322-0
doi: 10.1016/j.mcp.2019.01.003
pii:
doi:
Substances chimiques
HADHA protein, human
EC 1.1.1.211
Mitochondrial Trifunctional Protein, alpha Subunit
EC 1.1.1.211
HADHB protein, human
EC 2.3.1.16
Mitochondrial Trifunctional Protein
EC 2.3.1.16
Mitochondrial Trifunctional Protein, beta Subunit
EC 2.3.1.16
Types de publication
Case Reports
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
14-20Subventions
Organisme : Medical Research Council
ID : G1000848
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/N010035/1
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/N025431/1
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/N025431/2
Pays : United Kingdom
Informations de copyright
Copyright © 2019. Published by Elsevier Ltd.