2. Academic Validation
  3. A novel syndrome of Klippel-Feil anomaly, myopathy, and characteristic facies is linked to a null mutation in MYO18B

A novel syndrome of Klippel-Feil anomaly, myopathy, and characteristic facies is linked to a null mutation in MYO18B

  • J Med Genet. 2015 Jun;52(6):400-4. doi: 10.1136/jmedgenet-2014-102964.
Anas M Alazami 1,  Amal Y Kentab 2,  Eissa Faqeih 3,  Jawahir Y Mohamed 1,  Hisham Alkhalidi 4,  Hadia Hijazi 1,  Fowzan S Alkuraya 5
Affiliations

Affiliations

  • 1 Department of Genetics, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia.
  • 2 Department of Pediatrics, College of Medicine, King Saud University, Riyadh, Saudi Arabia.
  • 3 Department of Pediatric SubSpecialty, Children's Specialized Hospital, King Fahad Medical City, Riyadh, Saudi Arabia.
  • 4 Department of Pathology, College of Medicine, King Saud University, Riyadh, Saudi Arabia.
  • 5 Department of Genetics, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia Department of Anatomy and Cell Biology, College of Medicine, Alfaisal University, Riyadh, Saudi Arabia.
PMID: 25748484 DOI: 10.1136/jmedgenet-2014-102964
Abstract

Background: Klippel-Feil anomaly (KFA) can be seen in a number of syndromes. We describe an apparently novel syndromic association with KFA.

Methods: Clinical phenotyping of two consanguineous families followed by combined autozygome/exome analysis.

Results: Two patients from two apparently unrelated families shared a strikingly similar phenotype characterised by KFA, myopathy, mild short stature, microcephaly, and distinctive facies. They shared a single founder autozygous interval in which whole exome sequencing revealed a truncating mutation in MYO18B. There was virtually complete loss of the transcript in peripheral blood, indicative of nonsense-mediated decay. Electron microscopy of muscle confirms abnormal Myosin filaments with accompanying myopathic changes.

Conclusions: Deficiency of MYO18B is linked to a novel developmental disorder which combines KFA with myopathy. This suggests a widespread developmental role for this gene in humans, as observed for its murine ortholog.

Keywords

Myosin; Somite; exome; myopathy.

Figures