ZFIN ID: ZDB-PUB-150916-2
A novel mutation in DNAJB6, p.(Phe91Leu), in childhood-onset LGMD1D with a severe phenotype
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.
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 Continental Ancestry Group
  • 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.
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.