KIF1B – Charcot-Marie-Tooth disease type 2A1

KIF1B has been implicated in autosomal dominant Charcot-Marie-Tooth disease type 2A1 through the identification of a loss-of-function missense variant, c.293A>T (p.Gln98Leu), in a single proband (PMID:11389829). Functional studies demonstrate that Kif1b knockout mice die perinatally with neurologic and peripheral neuropathy-like defects, and that neuronal death can be rescued by expression of the KIF1Bβ isoform, supporting a haploinsufficiency mechanism (PMID:11389829). However, linkage and sequencing in a large Turkish CMT2A1 family mapped to the same 1p35-36 interval failed to identify any KIF1B mutation, suggesting locus heterogeneity in this region (PMID:15136675).

KIF1B encodes a kinesin-3 family motor protein critical for axonal transport of mitochondria and synaptic vesicle precursors; disruption of this function leads to distal axonal degeneration characteristic of CMT2A1. Given the single reported pedigree and evidence for additional disease loci, clinical screening for KIF1B variants may identify rare pathogenic alleles but negative results do not exclude a genetic diagnosis of CMT2A1.

References

• Cell • 2001 • Charcot-Marie-Tooth disease type 2A caused by mutation in a microtubule motor KIF1Bbeta. PMID:11389829
• Neurology • 2004 • Absence of KIF1B mutation in a large Turkish CMT2A family suggests involvement of a second gene. PMID:15136675

Evidence Based Scoring (AI generated)