A novel syndrome of Klippel-Feil anomaly, myopathy, and characteristic facies is linked to a null mutation in MYO18B.
PMID 25748484 | DOI 10.1136/jmedgenet-2014-102964 · Journal of medical genetics · 2015 · View on PubMed ↗
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.
Validated evidence
| Type | Entity | Source evidence | Confidence | Extractor |
|---|---|---|---|---|
| gene | MYO18B | “A novel syndrome of Klippel-Feil anomaly, myopathy, and characteristic facies is linked to a null mutation in MYO18B.” | 0.98 | hgnc_dict_v1 |
| phenotype | congenital myopathy | “A novel syndrome of Klippel-Feil anomaly, myopathy, and characteristic facies is linked to a null mutation in MYO18B.” | 0.93 | phenotype_alias_lexicon_v2 |
| population | Population | “METHODS: Clinical phenotyping of two consanguineous families followed by combined autozygome/exome analysis.” | 0.80 | saudi_context_rules_v1 |