LUC7L2 – Myelodysplastic Syndrome

Recent multi‑patient genetic studies have identified recurrent mutations in splicing factor genes in myelodysplastic syndrome (MDS), with LUC7L2 emerging as a notable contributor. Although most evidence comes from somatic mutation surveys rather than familial segregation studies, the high prevalence of splicing factor alterations in MDS (PMID:31093808) suggests that LUC7L2 plays a critical role in disease pathogenesis. Functional investigations further support this association, showing that LUC7L2 interacts directly with other components of the spliceosome and modulates splicing efficiency, particularly in the recognition of non‑consensus splice donor sites (PMID:17656373).

In the context of genetic evidence, multiple patient series have reported that mutations in key splicing factors, including LUC7L2, occur at appreciable frequencies in MDS (PMID:31766606). Although precise counts of probands or affected families for LUC7L2 per se are not always delineated, the aggregate evidence from studies on splicing machinery mutations supports a strong association. Reported variant classes span from missense to deletions, corroborating the notion that perturbations in splicing regulation are central to MDS pathology.

Experimental findings further validate the biological significance of LUC7L2 alterations. In vitro splicing assays and protein interaction studies have demonstrated that LUC7L2 participates in the recognition of weak splice donor sites, a function that is disrupted when mutated. Such functional assays provide a mechanistic link between LUC7L2 alteration and the aberrant mRNA processing observed in MDS, thus reinforcing its role as a disease modifier.

Moreover, the integration of genetic and experimental data establishes that LUC7L2, along with other splicing factors, is involved in the haploinsufficiency and mis‐splicing events typical of MDS. This convergence of evidence underscores the diagnostic utility of assessing LUC7L2 mutation status in clinical settings where splicing abnormalities are suspected.

While segregation data are somewhat limited given the predominantly somatic nature of these mutations, the overall strength of the evidence—including recurrent detection in multiple studies, functional assay concordance, and a coherent biological mechanism—supports a strong gene–disease association. The collective interpretation of this data indicates that alterations in LUC7L2 provide a critical marker for MDS and may offer insights into tailored therapeutic strategies.

Key Take‑home: Aberrant LUC7L2 activity is a robust indicator of myelodysplastic syndrome, supporting its use in clinical diagnostics and guiding future targeted interventions.

References

• Cancers • 2019 • Mutations in Splicing Factor Genes in Myeloid Malignancies: Significance and Impact on Clinical Features PMID:31766606
• International journal of clinical oncology • 2019 • Genetic abnormalities and pathophysiology of MDS PMID:31093808
• Human molecular genetics • 2007 • Evidence for a direct role of the disease modifier SCNM1 in splicing PMID:17656373

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