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.
- 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.
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.