Biallelic Variant in LYSET Associated With Mucolipidosis II-Like Phenotype.

Abstract

Dysostosis multiplex is a skeletal dysplasia often associated with lysosomal storage disorders (LSDs) such as mucopolysaccharidoses (MPS) and mucolipidoses (ML). Recently, pathogenic variants in the LYSET gene have been linked to a novel disorder resembling mucolipidosis types II/III (MLII/III). We report two Iranian brothers with homozygous pathogenic variants in LYSET (c.197dupA) who exhibit clinical, enzymatic, and radiographic features strikingly similar to MLII. Our findings reinforce the similarity between LYSET-related phenotypes and MLII, aligning with previously described cases. We propose the term "LYSET-related mucolipidosis" to describe this disorder and emphasize the importance of including LYSET in the genetic diagnostic panel for MLII/III-like presentations.