FUT7 and Hereditary Multiple Osteochondromas

Hereditary multiple osteochondromas (HMO) is an autosomal dominant skeletal disorder most commonly attributed to EXT1 mutations; however, recent evidence implicates FUT7 (HGNC:4018) as an additional contributor to the disease phenotype (PMID:39690272).

In a study employing whole‑exome sequencing in a Chinese family, a novel missense mutation in FUT7, designated as c.893T>G (p.Phe298Cys), was identified and shown to co‑segregate with HMO. This finding provides robust genetic evidence from a family trio design (PMID:39690272).

The genetic evidence supports an autosomal dominant inheritance pattern, with the reported variant being the sole coding change in FUT7 among the affected individuals. At least two affected relatives were observed to share the mutation, strengthening the genetic association (PMID:39690272).

Complementary functional studies revealed that the FUT7 mutation significantly alters the protein’s cellular localization and disrupts EXT1 expression through the IL6/STAT3/SLUG axis. Furthermore, a zebrafish model with concomitant loss of fut7 and ext1 recapitulated severe chondrodysplasia, providing functional evidence that aligns with the human phenotype (PMID:39690272).

No conflicting evidence regarding the role of FUT7 in HMO has been reported thus far; although classical HMO is predominantly linked to EXT1, these data suggest that FUT7 mutations may contribute via a potential 'second‑hit' mechanism.

In summary, the integration of genetic and functional data supports a strong association between FUT7 mutations and hereditary multiple osteochondromas. Key take‑home sentence: FUT7 should be considered for inclusion in diagnostic testing panels in HMO to improve molecular diagnosis and inform targeted therapeutic approaches.

References

• Oncogene • 2025 • Identification of novel germline mutations in FUT7 and EXT1 linked with hereditary multiple exostoses PMID:39690272

Evidence Based Scoring (AI generated)