Severe phenotype with cis-acting heterozygous PMP22 mutations

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Clin Genet. 2008 Nov 29.

Severe phenotype with cis-acting heterozygous PMP22 mutations.

Niedrist D, Joncourt F, Mátyás G, Müller A.

Institute of Medical Genetics, University of Zurich, Schwerzenbach,

Switzerland.

Niedrist D, Joncourt F, Mátyás G, Müller A. Severe phenotype with cis-

acting heterozygous PMP22 mutations. Clin Genet 2008.

We report on a 20-year-old male with severe Charcot-Marie-Tooth (CMT)

disease and a de novo deletion (c.281delG, p.G94AfsX17) on the

paternal PMP22 allele harboring c.353C>T (p.T118M).

RNA-based sequence analysis confirmed the absence of nonsense-

mediated decay and the presence of the mutant transcripts in Epstein-

Barr virus-transformed lymphoblastoid cells of our patient.

His clinical findings included early onset of polyneuropathy, loss of

muscle mass with distal pareses, hammer toes, and progressive

scoliosis.

There was no neuropsychological alteration. Our results suggest that

the deletion c.281delG alone is responsible for the severe CMT

phenotype.

To the best of our knowledge, this is the second report on a proven

paternal origin of a de novo single-base mutation in the PMP22 gene.