Objective:We found a special case in clinic:4 generations in a family were detected neuromuscular disorders. The symptoms included the upper elbows had different degrees of limited straight,lower limbs showed equines deformity,and feet were talipes cavus and were not detected obvious varus and adduction. This research aimed to study genetic mutation and molecular mechanism in crucial gene using whole-genome sequencing. Methods:Blood samples from sick child,father with the similar symptom and healthy mother were used to perform whole-genome sequencing by high-throughput sequencing technique. Bioinformatic analysis was used to filter gene mutations associated with disease. Further PCR validations were performed using blood samples from patients and healthy relatives in the family. Results:A series of gene mutations were obtained based on bioinformatics,including ANXA3 gene mutation(chr4,c.C820T(p.R274*)),HIST1H3A gene mutation (chr 6,c.C205T(p.Q69*)) and MTHFR gene mutation (c.T784C(p.Y262H)). PCR validation using blood samples from the family indicated that ANXA3 may be potential causing gene,and the mutation led to change of three-dimensional structure of ANXA3 protein. Conclusion:These results implicated that the ANXA3 may be related with the occurrence of the disease. This study provides certain reference for further understanding the genetic disease from the molecular levels.