FNBP4 and Microphthalmia with Limb Anomalies

Recent studies have identified a homozygous mutation in FNBP4 in a Lebanese family presenting with a phenotype consistent with microphthalmia with limb anomalies. The candidate variant, c.683C>T (p.Thr228Met), was discovered via whole‑exome sequencing and, along with homozygosity mapping, supports a potential role for FNBP4 in the disease pathogenesis (PMID:23703728). Although the evidence is bolstered by both case reports and multi‑patient studies, the genetic data is currently limited to a single proband with minimal additional segregation information.

Preliminary functional assessments also suggest that FNBP4 may modulate BMP signaling, a pathway integral to ocular and limb development, which is consistent with the observed phenotype. However, the experimental support remains modest and warrants further validation. The integration of genetic and functional findings, limited though they are, underscores the potential clinical utility of this association for diagnostic decision‑making and commercial applications. Key take‑home sentence: Despite its current limitations, the convergent evidence for FNBP4’s involvement in microphthalmia with limb anomalies suggests it may serve as a useful marker pending further research.

References

• American journal of medical genetics. Part A • 2013 • Whole‑exome sequencing identified a homozygous FNBP4 mutation in a family with a condition similar to microphthalmia with limb anomalies PMID:23703728

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