Dym-flox Mouse

Dym, associated with the OMIM number 607461, is a gene whose defects can cause skeletal dysplasias. Pathogenic variants in Dym have been reported to underlie Dyggve-Melchior-Clausen (DMC; OMIM 223800) dysplasia and Smith-McCort (SMC; OMIM 607326) dysplasia, indicating its importance in skeletal development [1].

In a study of large consanguineous families with osteochondrodysplasia phenotypes, homozygosity mapping and Sanger sequencing were used. A 9 Mb homozygous region on chromosome 18q21.1 harboring DYM was found shared by all available affected individuals. Sanger sequencing further revealed a novel homozygous nonsense variant [DYM (NM_017653.6):c.1205T>A, p.(Leu402Ter)] in affected individuals. This mutation leads to loss of protein stability and weakened interactions with other proteins, which are considered pathogenic [1].

In conclusion, Dym plays a crucial role in skeletal development, as evidenced by the identification of pathogenic variants in Dym associated with DMC and SMC dysplasias. The discovery of a novel nonsense variant in Dym and its associated effects on protein stability and interactions in affected individuals provides valuable insights into the molecular mechanisms underlying these skeletal dysplasias, which may contribute to prenatal screening, genetic counseling, and carrier testing.