Infantile demyelinating neuropathy associated with a de novo point mutation on Ser72 in PMP22 and basal lamina onion bulbs in skin biopsy.

Codon 72 has been designated as a hot spot for distinct missense mutations in the peripheral myelin protein 22 (PMP22) gene. Ser72Leu substitution was associated with Dejerine-Sottas syndrome (DSS) in four patients and with congenital hypomyelination neuropathy (CHN) in one patient. Our objective was to report one other DSS patient with Ser72Leu substitution in PMP22 and to concurrently illustrate how less invasive procedures such as skin biopsy could provide a rapid and reliable alternative to conventional sural nerve biopsy for the characterization of histophenotypic features. A skin biopsy was carried out in a 2 4/12-year-old girl with muscle atrophy, hypotonia and weakness, as well as generalized areflexia and absent sensory and motor nerve responses. Standard electron microscope techniques were used. PMP22 was screened by automated direct nucleotide sequencing analysis. Morphological examination revealed basal lamina onion bulbs surrounding a de- or hypomyelinated axon in all nerve bundles. Mutation analysis demonstrated a missense point mutation in codon 72 of the PMP22 gene leading to a Ser72Leu substitution. Further genotype-phenotype correlations will have to determine whether morphologically distinct phenotypes can be correlated with specific mutations. For this purpose, cutaneous nerve bundles could serve as an alternative tool to help identify and classify subtypes in this heterogeneous syndrome.