Azzedine et al. (2003) detected a homozygous nonsense mutation in the MTMR13 gene of a female with Charcot-Marie-Tooth neuropathy type 4B2 (CMT4B2) with early-onset glaucoma. Two other sibs, one females and one male, were also affected with CMT4B2 and early-onset glaucoma. The three affected sibs were the product of a consanguineous marriage. The affected sibs, their parents, and one other normal brother were genotyped with microsatellite markers. Also, linkage analysis, sequencing of the MTMR13 gene, RT-PCR, and polygenic analysis and protein domain prediction were performed. A nonsense mutation [2875C->T (Gln956Stop)] in exon 23 was identified in an affected female that was not presented in the normal control. That mutation was predicted to result in a truncated protein with deletion of the PTPc/DSPc and SID homology domains. Truncation of approximately half of the protein might also result in instability. MTMR13 was thought to be the first pseudophosphatase mutated in human disorders. Because there was apparently no complementation of MTMR13 loss of function by pseudophosphatase homologues in the target tissues, Azzedine et al. (2003) suggested that MTMR13 had a specific function in the peripheral nervous system and eye or that the level or pattern of expression of myotubularins differed.

Azzedine et al. (2003) identified a homozygous nonsense mutation in the MTMR13 gene of a female with Charcot-Marie-Tooth neuropathy type 4B2 (CMT4B2) and early-onset glaucoma. By studying the pedigree, three other females were also affected with CMT4B2 and early-onset glaucoma. The four affected females were the product of consanguineous marriages. The patients and other 15 normal family members were genotyped with microsatellite markers. Also, linkage analysis, sequencing of the MTMR13 gene, RT-PCR, and polygenic analysis and protein domain prediction were performed. A nonsense mutation [3586C->T (Arg1196 Stop)] in exon 27 was identified in an affected female that was not presented in the normal control. That mutation was predicted to result in a truncated protein with deletion of the PTPc/DSPc and SID homology domains. Truncation of approximately half of the protein might also result in instability.