PUBLICATION

A novel mutation in DNAJB6, p.(Phe91Leu), in childhood-onset LGMD1D with a severe phenotype

Authors
Nam, T.S., Li, W., Heo, S.H., Lee, K.H., Cho, A., Shin, J.H., Kim, Y.O., Chae, J.H., Kim, D.S., Kim, M.K., Choi, S.Y.
ID
ZDB-PUB-150916-2
Date
2015
Source
Neuromuscular disorders : NMD   25(11): 843-51 (Journal)
Registered Authors
Choi, Seok-Yong, Li, Wenting
Keywords
DNAJB6, Human genetics, Limb-girdle muscular dystrophy, Magnetic resonance imaging, Zebrafish
MeSH Terms
  • Adult
  • Age of Onset
  • Animals
  • Animals, Genetically Modified
  • Asian People
  • Child
  • Diagnosis, Differential
  • Family
  • Female
  • HSP40 Heat-Shock Proteins/genetics*
  • HSP40 Heat-Shock Proteins/metabolism
  • Humans
  • Male
  • Middle Aged
  • Molecular Chaperones/genetics*
  • Molecular Chaperones/metabolism
  • Muscle, Skeletal/pathology
  • Muscle, Skeletal/physiopathology
  • Muscular Dystrophies, Limb-Girdle/diagnosis
  • Muscular Dystrophies, Limb-Girdle/genetics*
  • Muscular Dystrophies, Limb-Girdle/pathology
  • Muscular Dystrophies, Limb-Girdle/physiopathology
  • Mutation, Missense*
  • Nerve Tissue Proteins/genetics*
  • Nerve Tissue Proteins/metabolism
  • Phenotype
  • Sequence Homology, Amino Acid
  • Severity of Illness Index
  • Zebrafish
PubMed
26371419 Full text @ Neuromuscul. Disord.
Abstract
To identify and characterize genetic mutation in a Korean family with limb-girdle muscular dystrophy 1 (LGMD1), we analyzed in the affected family members clinical features, DNAJB6 by Sanger sequencing, muscle structures by magnetic resonance imaging (MRI), and functional consequences of the identified mutation using a zebrafish model. The clinical phenotypes along with identification of a novel c.271T > C (p.(Phe91Leu)) mutation in DNAJB6 led to the diagnosis of LGMD1D in the affected family members. This mutation presents unique clinical and radiological features compared with other DNAJB6 mutants. All affected members examined showed reduced pulmonary function, and had nasal voice and dysphagia except the two members who were thirteen and twelve years of age at the time of examination. Muscle phenotypes developed between 8 and 11 years of age and were more severe as compared to previously reported LGMD1D patients with mutant DNAJB6. Patients' MRI scans exhibited early involvement of the lateral head of gastrocnemius, in contrast to its late involvement in reported LGMD1D cases. Functional study using zebrafish embryos demonstrated that p.Phe91Leu elicits more severe muscle defects than the reported p.Phe93Leu and p.Pro96Arg mutations. We conclude that a novel p.(Phe91Leu) mutation in DNAJB6 is associated with severe childhood-onset LGMD1D.
Genes / Markers
Figures
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping