SBF1 – Charcot-Marie-Tooth disease type 4B3

Evidence for SBF1 involvement in Charcot-Marie-Tooth disease type 4B3 (CMT4B3) remains limited. A novel heterozygous missense variant, c.1398C>A (p.His466Gln), was identified in a mother–daughter pair with early-onset distal limb amyotrophy, normal nerve conduction velocities, and autosomal dominant transmission (PMID:39664754). Separately, three unrelated CMT4B3 patients harboring homozygous SBF1 mutations have been used to generate induced pluripotent stem cell lines, providing a resource to study MTMR5 dysfunction but not yet yielding phenotypic rescue or in vivo confirmation (PMID:39461113). Additionally, targeted sequencing of 612 hereditary neuropathy cases detected rare SBF1 loss-of-function alleles among diverse CMT and related neuropathies, suggesting recurring mutation across neuropathic phenotypes (PMID:28902413). Biallelic truncating variants co-segregate in two families with autosomal recessive axonal neuropathy and additional cranial involvement, supporting a wider phenotypic spectrum but lacking large pedigrees or functional validation in vivo (PMID:28005197). The heterogeneity of inheritance (dominant vs recessive), small family sizes, and absence of robust animal or rescue studies limit the current clinical validity of SBF1–CMT4B3. Key take-home: while rare SBF1 variants segregate with neuropathy in few families and iPSC models exist, additional large pedigrees and functional rescue experiments are needed before routine diagnostic use.

References

• Frontiers in neurology • 2024 • A novel SBF1 missense mutation causes autosomal dominant Charcot-Marie-Tooth disease type 4B3 PMID:39664754
• Stem cell research • 2024 • Establishment and characterization of three human pluripotent stem cell lines from Charcot-Marie-Tooth disease Type 4B3 patients bearing mutations in MTMR5/Sbf1 gene PMID:39461113
• Journal of neurochemistry • 2017 • Frequent genes in rare diseases: panel-based next generation sequencing to disclose causal mutations in hereditary neuropathies PMID:28902413
• Neurogenetics • 2017 • SBF1 mutations associated with autosomal recessive axonal neuropathy with cranial nerve involvement PMID:28005197

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