Rare among Rare: Phenotypes of Uncommon CMT Genotypes.

(1) Background: Charcot-Marie-Tooth disease (CMT) is the most frequent form of inherited chronic motor and sensory polyneuropathy. Over 100 CMT causative genes have been identified. Previous reports found , , , and as the most frequently involved genes. Other genes, such as , , , , , and autosomal dominant are responsible for only a minority of CMT cases. (2) Methods: we present here our records of CMT patients harboring a mutation in one of these rare genes (, , , , , autosomal dominant ). We studied 17 patients from 8 unrelated families. All subjects underwent neurologic evaluation and genetic testing by next-generation sequencing on an Ion Torrent PGM (Thermo Fischer) with a 44-gene custom panel. (3) Results: the following variants were found: c.263A > G p.Asn88Ser (eight subjects), c.1503A > T p.Gln501His (one subject), c.110G > C p.Arg37Pro (one subject), c.404C > G p.Pro135Arg (two subjects), c.1660G > A p.Asp554Asn (three subjects), c.374G > A p.Arg125Gln (two subjects). (4) Expanding the spectrum of CMT phenotypes is of high relevance, especially for less common variants that have a higher risk of remaining undiagnosed. The necessity of reaching a genetic definition for most patients is great, potentially making them eligible for future experimentations.