Lupski et al. (2010) reported a 3-generation family with variable severity of a peripheral neuropathy. The family was ascertained through 4 sibs with a phenotype consistent with autosomal recessive CMT4C caused by compound heterozygous mutations in the SH3TC2 ... Lupski et al. (2010) reported a 3-generation family with variable severity of a peripheral neuropathy. The family was ascertained through 4 sibs with a phenotype consistent with autosomal recessive CMT4C caused by compound heterozygous mutations in the SH3TC2 gene: R954X (608206.0005) and Y169H (608206.0008). Three additional family members who were heterozygous for the R954X mutation, resulting in loss of function, had a subtle mild mononeuropathy of the median nerve (MNMN) consistent with carpal tunnel syndrome. This involvement of the median nerve was also seen in the patients with CMT4C. Lupski et al. (2010) concluded that haploinsufficiency of SH3TC2 may confer susceptibility to carpal tunnel syndrome. Two additional family members who were heterozygous for the Y169H mutation had an apparently autosomal dominant patchy axonal polyneuropathy, as shown by electrophysiologic studies. They had a definite median nerve mononeuropathy at the wrist associated with evidence of a more widespread axonal neuropathy. The phenotype was similar to that of hereditary neuropathy with liability to pressure palsies (HNPP; 162500). The authors postulated a toxic gain of function for the Y169H-mutant protein. Lupski et al. (2010) commented on the subtle, apparently autosomal dominant phenotypes segregating independently with the respective SH3TC2 mutations.