A novel syndrome of Klippel-Feil anomaly, myopathy, and characteristic facies is linked to a null mutation in MYO18B.
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.
Department of Genetics, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia.
Anas M
AM
Alazami
Department of Pediatrics, College of Medicine, King Saud University, Riyadh, Saudi Arabia.
Amal Y
AY
Kentab
Department of Pediatric SubSpecialty, Children's Specialized Hospital, King Fahad Medical City, Riyadh, Saudi Arabia.
Eissa
E
Faqeih
Department of Genetics, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia.
Jawahir Y
JY
Mohamed
Department of Pathology, College of Medicine, King Saud University, Riyadh, Saudi Arabia.
Hisham
H
Alkhalidi
Department of Genetics, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia.
Hadia
H
Hijazi
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.
Fowzan S
FS
Alkuraya
D000293:Adolescent; D002648:Child; D002874:Chromosome Mapping; D003241:Consanguinity; D004252:DNA Mutational Analysis; D019066:Facies; D005260:Female; D006720:Homozygote; D006801:Humans; D007714:Klippel-Feil Syndrome / Q000175:diagnosis* / Q000235:genetics*; D008297:Male; D018482:Muscle, Skeletal / Q000473:pathology / Q000648:ultrastructure; D009135:Muscular Diseases / Q000175:diagnosis* / Q000235:genetics*; D009154:Mutation; D009218:Myosins / Q000235:genetics*; D010375:Pedigree; D010641:Phenotype; D013131:Spine / Q000473:pathology; D013577:Syndrome; D025521:Tumor Suppressor Proteins / Q000235:genetics*
C500982:MYO18B protein, human; D025521:Tumor Suppressor Proteins; D009218:Myosins
Myosin; Somite; exome; myopathy