Upregulation of the Four and a Half LIM Domains 1 linked with familial venous dysplasia in a familial genetic examination.

BACKGROUND

This study aimed to analyze the mutation site in a family diagnosed with venous dysplasia to identify possible pathogenic genes.

METHODS

A 15-year-old female presented with lower extremity venous tortuosity aggravated by ulceration. Only the young sister exhibited similar symptoms within the immediate family of the proband. Whole genome sequencing (WGS) was used to evaluate the mutation sites and chromosome copy number variations (CNV) within the family. The possible pathogenic genes located in the region with CNVs were identified, and the expression of the possible pathogenic genes was verified via quantitative polymerase chain reaction (Q-PCR) and western blotting (WB) analysis. In-vitro models were used to verify the role of possible pathogenic genes linked with the development of venous dysplasia.

RESULTS

The high-resolution karyotype analysis of the chromosomes found no abnormalities. The results of the WGS indicated that the proband and her sister shared the CNV events, including a microdeletion on chromosomes X: 13580000-1358555000 and microduplications of chromosome X: 136055000-136290000, chromosome X: 136475000-13671000. The results of the Q-PCR and WB showed that FHL1 was highly expressed in the proband and her sister, indicating that mutations of the FHL1 may have an important role in the development of vein malformations. The results of the in vitro experiments showed that FHL1 overexpression could inhibit venous development.

CONCLUSION

The CNV in the Xq26 region (136054501-136288300) was found to be linked with the development of venous malformations in this family. However, further studies are required to evaluate the genetic mechanisms involved in the development of venous malformations.