HLX – Congenital Diaphragmatic Hernia

This summary details the association between HLX and congenital diaphragmatic hernia, integrating genetic and functional evidence from multiple studies. In a pivotal analysis of 119 CDH probands, four unique HLX missense variants were identified, including the variant c.517G>T (p.Asp173Tyr) (PMID:19459883). Although one variant was maternally inherited and segregation data remain limited, these findings, together with candidate gene lists derived from CNV studies in CDH (PMID:23054247), support a modest contribution of HLX variants to the phenotype. The overall gene-disease association is therefore classified as Limited, considering the modest number of probands and the absence of robust segregation or extensive functional data.

Functional assessments have demonstrated the expression of HLX in the developing murine diaphragm, particularly at the diaphragm-liver junction, which is relevant to the pathogenesis of diaphragmatic hernia (PMID:19459883). However, reporter assays failed to demonstrate significant differences in transcriptional activity between wild-type and variant HLX constructs, leaving the mechanism of pathogenicity unclear. Overall, while current evidence supports the candidacy of HLX in CDH, its clinical utility may be enhanced by further genetic and functional analyses. Key take‑home: HLX screening in cases of congenital diaphragmatic hernia can provide valuable insights, although further studies are needed to fully establish its role.

References

• Clinical genetics • 2009 • Sequence variants in the HLX gene at chromosome 1q41-1q42 in patients with diaphragmatic hernia. PMID:19459883
• Journal of medical genetics • 2012 • De novo copy number variants are associated with congenital diaphragmatic hernia. PMID:23054247

Evidence Based Scoring (AI generated)