Clinical Neuroscience

[The modifying effect a PMP22 deletion in a family with Charcot-Marie-Tooth type 1 neuropathy due to an EGR2 mutation]

REMÉNYI Viktória1, INCZÉDY-FARKAS Gabriella1,2, GÁL Anikó1, BEREZNAI Benjámin1, PÁL Zsuzsanna3, KARCAGI Veronika4, MECHLER Ferenc5, MOLNÁR Mária Judit1

NOVEMBER 28, 2014

Clinical Neuroscience - 2014;67(11-12)

[Background - Mutations of both the PMP22 and EGR2 genes cause Charcot-Marie-Tooth (CMT) disease type 1. Deletion of the PMP22 gene, results in hereditary neuropathy with liability to pressure palsies. More publications exist about the interaction of PMP22 duplication and other CMTcausing gene mutations. In these cases the intrafamiliar discordant phenotypes draw the attention to the possible role of modifying genes. The gene-gene interactions between the PMP22 and EGR2 genes are not well understood. Case report - We report two brothers with late onset CMT1 due to a c. 1142 G>A (Arg381His) heterozygous substitution in the EGR2 gene. Additionally, the older brother with the less severe symptoms harbored the PMP22 gene deletion also. Conclusion - The coexistence of the two genetic alterations did not aggravate the clinical symptoms. Moreover, the PMP22 deletion appeared to have a beneficial modifying effect, thus implying potential gene-gene interaction of PMP22 and EGR2. PMP22 deletion may increase Schwann cells proliferation and compensate the dominant-negative effect of the Arg381His substitution in the EGR2 gene.]

AFFILIATIONS

  1. Institute of Genomic Medicine and Rare Disorders, Semmelweis University, Hungary
  2. Zucker Hillside Hospital North Shore - LIJ Health System, Glen Oaks, NY, USA
  3. Department of Neurology, Semmelweis University, Hungary
  4. National Institute of Environmental Health, Department of Molecular Genetics
  5. Department of Neurology, University of Debrecen, Hungary

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