Compound heterozygous splicing and missense variants in MYO7A in a Chinese patient with Usher syndrome

The objectives of the present study were to identify the genetic variations in a Chinese patient with Usher syndrome and to determine the pathogenicity of the identified variations.

Whole-exome sequencing was performed for the proband. Alphafold3 and PyMOL software were used to determine the impact of a variation on three-dimensional protein structure. A Minigene Splicing Assay was performed to investigate the impact of a variant on MYO7A splicing.

Two compound heterozygous missense and splicing variations of MYO7A (NM_000260:c.487G > A:p.G163R, rs1472566324 and c.2187 + 2_2187 + 8del, rs1416744060) were identified in the proband. After glycine (G, WT) is replaced by arginine (R, rs1472566324), arginine forms additional hydrogen bonds with the surrounding amino acids. In the Minigene Splicing Assay, abnormal splicing bodies (associated with an Exon18 jump) were observed in the mutant plasmids (rs1416744060). This abnormal splicing event caused a deletion of 31 aa inside the protein, generating a truncated protein of 2,184 aa.

Compound heterozygous missense and splicing variants of MYO7A (rs1472566324 and rs1416744060) were the likely pathogenic variants of a patient with Usher syndrome type 1B.