FAR2 and Kallmann Syndrome

This summary synthesizes the current evidence linking FAR2 (HGNC:25531) to Kallmann syndrome (MONDO_0018800). In a multi‐patient study, a heterozygous missense variant, c.352G>A (p.Asp118Asn) (PMID:37034680), was identified in a KS patient, and FAR2 has been nominated among candidate genes for KS with intellectual disability through CNV analyses. A complementary study of subjects carrying small copy number variations in the 12p11.21-12p11.23 region further implicated FAR2 as a potential contributor to the phenotype (PMID:37563198). Despite these findings, only a limited number of probands have been reported, with no extended segregation data, which confines the overall strength of the evidence.

Functional assessments support the candidacy of FAR2 by demonstrating its high-level expression in disease-relevant tissues, suggesting that dosage alterations could disrupt normal developmental processes. However, the absence of extensive segregation analysis and robust functional model validation means that the gene-disease association remains preliminary. Further studies involving point mutation screening and additional functional assays are needed to fully ascertain FAR2’s pathogenic role. Key take‑home: While FAR2 is a promising candidate, its current evidence level is limited, necessitating further validation before it can be integrated into routine diagnostic decision‑making.

References

• Unspecified Journal • 2023 • Study implicating FAR2 in Kallmann syndrome PMID:37034680
• Scientific Reports • 2023 • A cryptic microdeletion del(12)(p11.21p11.23) within an unbalanced translocation implicates new candidate loci for intellectual disability and Kallmann syndrome PMID:37563198

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