SET binding factor 1 ( SBF1 ) mutation causes Charcot-Marie-Tooth disease type 4B3

Abstract

We suggest that the compound heterozygous mutations in SBF1 are the underlying causes of a novel CMT4B subtype, designated as CMT4B3. We believe that this study will lead to mechanistic studies to discover the function of SBF1 and to the development of molecular diagnostics for CMT disease.

The Guillain–Barrè peptide signatures: from Zika virus to Campylobacter, and beyond

“…77,78 MTMR2 appears to negatively regulate membrane homeostasis in Schwann cell myelination. 79 Another myotubularin-related protein, namely MTMR5, shares eight pentapeptides with ZIKV (eg, AVLLR, GPSLR, GLLIV, LQDGL, REEGA, SEELE, SLGLI, and VLSMV) and many of the said pentapeptides are also present in infectious agents (Table 1). MTMR5 pentapeptide sharing is noteworthy.…”

“…MTMR5 pentapeptide sharing is noteworthy. Indeed, alterations of MTMR5 are involved in demyelinating neuropathies 79 and, in addition and most interestingly, lead to impaired spermatogenesis. [80][81][82] This datum might be a hint for widening the study of the still obscure reasons for gender differences in GBS pathogenesis.…”

Splicing mutation in Sbf1 causes nonsyndromic male infertility in the rat

“…observed normal phenotype of heterozygotes would be less likely in presence of a truncated protein that could disrupt the protein complexes, presumably MTMR2/Sbf2, that require SBF1. It was shown recently that human homozygotes or compound heterozygotes for missense SBF1 mutations exhibit hereditary progressive neuropathy CharcotMarie-Tooth disease type 4B3 (Nakhro et al 2013, Alazami et al 2014. There is no neurological impairment even in old SHR ifm/ifm rats, nor there was reported any such phenotype for the knockout mice (Firestein et al 2002).…”

“…Mice lacking SBF1 are viable, with isolated male infertility due to spermatogenesis failure resulting in azoospermia (Firestein et al 2002). Human homozygotes or compound heterozygotes for damaging missense mutations develop Charcot-MarieTooth demyelinating peripheral neuropathy (Nakhro et al 2013, Alazami et al 2014. Here, we report a splicing site mutation leading to truncation of the rat SBF1 ortholog, which closely resembles the null mice with male infertility as principal pathological finding.…”

Autosomal recessive demyelinating or axonal Charcot–Marie–Tooth neuropathy

“…This AR demyelinating CMT subtype is caused by compound heterozygous mutations in the SET binding factor 1 encoding gene (SBF1), also called MTMR5, and has thus far been identified in only one Korean family, using whole exome sequencing [53].…”