Type 1A and Mutations Research from Brazil

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Abstract from Brazilian Journal Med Biol Res. 2003 Oct;36(10):1403-7.

Thr(118)Met amino acid substitution in the peripheral myelin protein 22

does not influence the clinical phenotype of Charcot-Marie-Tooth disease

type 1A due to the 17p11.2-p12 duplication.

Marques Jr W, Sweeney MG, Wood NW.

Departamento de Neurologia, Faculdade de Medicina de Ribeir o Preto,

Universidade de S o o, Ribeir o Preto, SP, Brasil.

The Thr(118)Met substitution in the peripheral myelin protein 22 (PMP22)

gene has been detected in a number of families with demyelinating

Charcot-Marie-Tooth (CMT1) neuropathy or with the hereditary neuropathy

with liability to pressure palsy, but in none of

them has it consistently segregated with the peripheral neuropathy. We

describe here a CMT1 family (a 63-year-old man, his brother and his

niece) in which two mutations on different chromosomes were found in the

PMP22 gene, the 17p duplication, detected by fluorescent

semiquantitative polymerase chain reaction (PCR) of microsatellite

markers localized within the duplicated region on chromosome

17p11.2-p12, and the Thr(118)Met substitution, detected by direct

sequencing the four coding exons of the PMP22 gene. A genotype/phenotype

correlation study showed that the neuropathy

segregates with the duplication and that the amino acid substitution

does not seem to modify the clinical characteristics or the severity of

the peripheral neuropathy. We did not find any evidence to characterize

this substitution as a polymorphism in the population studied and we

propose that the high frequency reported for this point

mutation in the literature suggests that the Thr(118)Met substitution

may be a hotspot for mutations in the PMP22 gene.