Congenital hypomyelinating neuropathy due to the association of a truncating mutation in PMP22 with the classical HNPP deletion

Neuromuscul Disord. 2016 Apr-May;26(4-5):316-21. doi: 10.1016/j.nmd.2016.01.004. Epub 2016 Apr 5.

Abstract

Congenital hypomyelinating neuropathy appears early in life, resulting in a delay of motor and sensory development. Mutations involve genes such as myelin protein zero (MPZ), peripheral myelin protein 22 (PMP22), and early growth response 2 (EGR2). We present a patient with two compound mutations in PMP22: a point mutation causing a premature STOP codon in exon 3 was inherited from the mother on the first allele, and the "typical" PMP22 deletion in the 17p11.2-p12 region was inherited from the father on the other allele. A sural biopsy was performed at age four. The patient has been followed from 28 months to 21 years of age; he presented significant sensory disturbances, with a slight motor deficit. PMP22 mRNA quantitation showed a severe decrease of PMP22 protein. No myelin sheaths were observed in the biopsy; mesaxons failed to form. The absence of PMP22 provides new insights into the role of this protein.

Keywords: CMT; Congenital hypomyelinating neuropathy; Nerve biopsy; PMP22.

Publication types

  • Case Reports

MeSH terms

  • Biopsy
  • Charcot-Marie-Tooth Disease / genetics*
  • Charcot-Marie-Tooth Disease / pathology
  • Charcot-Marie-Tooth Disease / physiopathology
  • Child, Preschool
  • Humans
  • Male
  • Myelin Proteins / genetics*
  • Myelin Proteins / metabolism
  • Neural Conduction / genetics
  • Point Mutation*
  • RNA, Messenger / metabolism
  • Sequence Deletion*
  • Sural Nerve / pathology
  • Sural Nerve / physiopathology
  • Young Adult

Substances

  • Myelin Proteins
  • PMP22 protein, human
  • RNA, Messenger

Supplementary concepts

  • Charcot-Marie-Tooth disease, Type 4E