Molecular characteristics: The MYH10-related disorder is inherited in an autosomal dominant fashion. The vast majority of variants are de novo; however, inheritance from a mildly affected parent has been reported. Most variants reported are missense affecting most protein domains with an emerging hot spot in the motor domain. Loss-of-function variants have also been reported. There are currently no genotype-phenotype correlations.
Diagnostic testing: sequencing and deletion/duplication analysis of the MYH10 gene.
Mechanism: MYH10 encodes for the non-muscle myosin heavy chain IIB. MYH10 is a part of the myosin 2 family and is primarily expressed in non-muscle cell types. MYH10 exerts tension on the actin network and broadly influences actin dynamics. MYH10 has also been implicated in the biogenesis and function of the primary cilium. Loss of MYH10 function can lead to defects in primary ciliogenesis, ciliary length defects, and abnormal Hedgehog signalling. Many of the phenotypic findings can be associated with altered Hedgehog signalling. Mouse models of altered MYH10 activity also recapitulate many aspects of the phenotypic presentation of the disorder.
MYH10