Novel GZF1 Pathogenic Variants Identified in Two Chinese Patients with Larsen Syndrome.

GZF1 was recently reported as a genetic factor associated with Larsen syndrome. Two patients presenting hip dislocation, scoliosis and severe myopia, as well as hearing loss and other abnormal features, were found to carry two novel compounds heterozygous variants inGZF1(c.397400del, p. Leu133fs; and c.1474del, p. Met492fs) through whole-exome sequencing. The mRNA expression level of L133fs-GZF1did not significantly differ from that of WT-GZF1. However, no HA-conjugated mutant protein was detected by western blotting, which was also confirmed by immunofluorescence staining. In addition, both mRNA transcription and protein expression levels of M492fs-GZF1were significantly lower than those of wild type, and HA-tagged M492fs-GZF1 was mainly distributed in the cytoplasm of HEK 293 T cells. These results suggested that the two variants could lead to loss of function ofGZF1. Our study was the second to report the association betweenGZF1variants and Larsen syndrome. We also provided functional evidence for the pathogenicity ofGZF1variants, which expands the mutation spectrum and offers a basis for functional research on the role ofGZF1in the development of Larsen syndrome.