Disease relevance of SBF2

• It is striking to note that mutations in MTMR13 also cause peripheral neuropathy with myelin outfoldings, although it belongs to a pseudophosphatase subgroup, since its closest homologue is MTMR5/Sbf1 [1].
• MTM1 is mutated in X-linked myotubular myopathy, and MTMR2 and MTMR13 are mutated in Charcot-Marie-Tooth syndrome [2].

High impact information on SBF2

• In these two families, we identified two different nonsense mutations in the myotubularin-related 13 gene, MTMR13 [1].
• We mapped this syndrome to chromosome 11p15, in a 4.6-cM region overlapping the locus for an isolated demyelinating ARCMT (CMT4B2) [1].
• MTMR13 may be important for the development of both the peripheral nerves and the trabeculum meshwork, which permits the outflow of the aqueous humor [1].
• On membranes of large vesicles formed under hypo-osmotic conditions, Sbf2 favorably competes with Mtmr2 for binding sites [3].
• Mutation of the SBF2 gene, encoding a novel member of the myotubularin family, in Charcot-Marie-Tooth neuropathy type 4B2/11p15 [4].

Biological context of SBF2

• Molecular study of the SBF2 gene in the CMT4B family demonstrated the presence of a homozygous inframe deletion of SBF2 exons 11 and 12 in all four affected individuals [4].
• Localization of SBF2 within the candidate interval, cosegregation with the disease, expression in the peripheral nervous system, and resemblance of the histopathological phenotype to that related to mutations in its paralogue MTMR2 indicate that this gene is the CMT4B2 gene [4].
• Autosomal recessive CMT is genetically heterogeneous with one locus mapped to chromosome 11p15 (CMT4B2) [4].
• Since SBF1 governs the formation kinetics and composition of the initial precursor spheres, we hypothesized that the pH of the SBF1 solution will also influence the final structure of the SBF2-derived crystalline apatite [5].
• The consistent phenotypic features associated with SBF2 mutations are early-onset demyelinating neuropathy, myelin folding, and markedly decreased motor nerve conduction velocities; glaucoma associates with SBF2 nonsense mutations [6].

Anatomical context of SBF2

• The histopathological hallmarks of CMT4B2 are focal outfoldings of myelin in nerve biopsies [4].
• We identified a large, novel gene, named SET binding factor 2 (SBF2), that lies within this interval and is expressed in various tissues, including spinal cord and peripheral nerve [4].

Associations of SBF2 with chemical compounds

• To test this hypothesis, polystyrene substrates were immersed into SBF1 with different pH (5.8 or 6.5), and then immersed into the identical SBF2 (pH=6.0) [5].
• The MTMR13 phosphatase domain is catalytically inactive because the essential Cys and Arg residues are absent [7].

Other interactions of SBF2

• The authors report a Japanese family segregating autosomal recessive Charcot-Marie-Tooth disease (CMT) with focally folded myelin, juvenile-onset glaucoma, and a nonsense mutation of SET binding factor 2 (SBF2) [6].

Analytical, diagnostic and therapeutic context of SBF2

• Here, we describe the molecular cloning and the expression pattern of Sbf2 [8].
• In situ hybridization, Northern blots and RT-analysis revealed a very broad pattern of Sbf2 expression [8].

References