CMTM7 and Mayer-Rokitansky-Kuster-Hauser Syndrome

In a recent study, a 17-year-old female with Mayer-Rokitansky-Kuster-Hauser syndrome was shown to carry a de novo balanced chromosomal translocation—46,XX,t(3;16)(p22.3;p13.3) (PMID:27478502). Although no coding mutation was detected in the nearby candidate genes, detailed molecular mapping highlighted CMTM7 (HGNC:19178) as a potential candidate due to its significantly reduced expression in the proband compared to white female controls. The study employed RT‑qPCR to quantify gene expression across 20 genes near the breakpoints, with CMTM7 among the genes showing aberrant levels. These findings, however, come from a single proband and lack additional segregation data or independent replication in other families. The limited genetic data, combined with a focused but singular functional assay, restricts the current weight of evidence for a direct causal role of CMTM7 in the disorder. As such, the genetic evidence must be considered preliminary for clinical decision‑making.

The functional assessment further supports a potential role for CMTM7 through altered expression, yet comprehensive functional studies (e.g. animal models, rescue experiments) are absent at this point. This leaves the pathogenic mechanism—whether haploinsufficiency or another mode—as still to be fully elucidated. Overall, while the observed expression change is intriguing, the limited genetic and functional evidence suggests that more multi‐patient studies and mechanistic investigations are necessary. The key take‑home is that while CMTM7 emerges as a novel candidate gene in the context of MRKH syndrome, its current clinical utility remains limited pending further validation.

References

• Molecular cytogenetics • 2016 • A balanced chromosomal translocation involving chromosomes 3 and 16 in a patient with Mayer-Rokitansky-Kuster-Hauser syndrome reveals new candidate genes at 3p22.3 and 16p13.3 PMID:27478502

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