Two families with novel PMP22 point mutations: genotype–phenotype correlation

We report two novel PMP22 point mutations identified\udin two unrelated families with a moderate and\udslowly progressive Charcot-Marie-Tooth type 1 (CMT1)\udphenotype, with the exception of the proband of Family\ud2 who presented a clinical picture complicated\udby perinatal asphyxia. Nerve conduction study (NCS)\udrevealed very slow motor nerve conduction velocities\udand sural nerve biopsy, performed in one patient,\udshowed severe demyelination and hypomyelination.\udIn the first family, a missense mutation (Leu78Pro)\udwas identified, whereas in the second family a nonsense\udmutation (Gln103X) was found. Both families\udhad clinical and neurophysiological aspects overlapping\udbetween CMT1 and Dejerine-Sottas syndrome\ud(DSS). We point out that the type of PMP22 point\udmutations, the nature of the amino acid change, as\udwell as the position of the altered amino acid play a\udrole in determining the severity of the clinical picture.\udCharcot-Marie-Tooth disease (CMT) is the most\udcommon inherited peripheral neuropathy and it\udincludes a group of clinically and genetically\udheterogeneous disorders. CMT type 1A is the most\udcommon form of CMT and is caused by a duplication\udof a 1.5 Mb region on chromosome 17 that includes\udthe gene encoding the peripheral myelin protein 22\ud(PMP22). Point mutations in PMP22, far less common\udthan duplication, also cause CMT1A (Reilly, 2007).\udHerein, we describe clinical, electrophysiological,\udand molecular findings of two CMT1 families carrying\udtwo novel mutations of the PMP22 gene