MYH3 – Contractures, Pterygia, and Spondylocarpotarsal Fusion Syndrome 1A

A heterozygous variant in MYH3 has been identified as the cause of autosomal dominant Contractures, Pterygia, and Spondylocarpotarsal Fusion Syndrome 1A. In a five-generation Chinese family, whole-exome sequencing and Sanger validation uncovered a novel in-frame indel, c.3044_3047delinsTCAATTTGTT (p.Glu1015_Asp1016delinsValAsnLeuPhe), that cosegregated with disease in six affected relatives (PMID:32767732).

The condition is characterized by congenital joint contractures, pterygia, and vertebral fusion. Segregation analysis in this pedigree provides strong co-segregation evidence across six affected individuals, but no additional unrelated cases have been reported. Functional assays—including in silico modeling, Western blotting, and histopathology of fetal muscle—did not reveal significant loss or gain of protein function, suggesting a potential dominant-negative or subtle conformational effect not detectable by routine protein expression studies (PMID:32767732).

References

• Molecular genetics & genomic medicine • 2020 • Identification of a novel pathogenic variant in the MYH3 gene in a five-generation family with CPSFS1A (Contractures, Pterygia, and Spondylocarpotarsal Fusion Syndrome 1A). PMID:32767732

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