title: Severe phenotypes in a Charcot-Marie-Tooth 1A patient with PMP22 triplication.
abstract: Charcot-Marie-Tooth disease (CMT) is a genetically and clinically heterogeneous hereditary motor and sensory neuropathy signified by a distal symmetric polyneuropathy. The most frequent subtype is type 1A (CMT1A) caused by duplication in chromosome 17p12 that includes PMP22. This study reports a woman with a family history of CMT1A due to PMP22 duplication. However, she presented with a more severe phenotype than her sibling or ancestors and was found to have a PMP22 triplication instead of the duplication. This was caused by de novo mutation on her affected mother's duplication chromosome. Her lower limb magnetic resonance imaging revealed severe diffused atrophy and fatty replacement. However, her affected sister with typical PMP22 duplication showed almost intact lower limb. Triplication patient's median motor nerve conduction velocity was far lower compared with her sister. Her onset age was faster (8 years) than her sister (42 years). CMT1A triplication might be generated by a female-specific chromosomal rearrangement mechanism that is different from the frequent paternal-originated CMT1A duplication. It also suggests that the wide phenotypic variation of CMT1A might be partly caused by unstable genomic rearrangement, including PMP22 triplication.
authors.affiliation: Department of Biological Science, Kongju National University, Gongju, Korea.
authors.forename: Sung Min
authors.initials: SM
authors.lastname: Kim
authors.affiliation: Department of Neurology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Jinho
authors.initials: J
authors.lastname: Lee
authors.affiliation: Department of Biological Science, Kongju National University, Gongju, Korea.
authors.forename: Bo Ram
authors.initials: BR
authors.lastname: Yoon
authors.affiliation: Department of Biological Science, Kongju National University, Gongju, Korea.
authors.forename: Ye Jin
authors.initials: YJ
authors.lastname: Kim
authors.affiliation: Department of Neurology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Byung-Ok
authors.initials: BO
authors.lastname: Choi
authors.affiliation: Department of Biological Science, Kongju National University, Gongju, Korea.
authors.forename: Ki Wha
authors.initials: KW
authors.lastname: Chung
mesh_terms: D000328:Adult; D017668:Age of Onset; D002607:Charcot-Marie-Tooth Disease / Q000235:genetics* / Q000473:pathology; D002886:Chromosomes, Human, Pair 17 / Q000235:genetics; D004252:DNA Mutational Analysis; D005192:Family Health; D005260:Female; D018628:Gene Dosage; D020440:Gene Duplication; D006801:Humans; D008297:Male; D008875:Middle Aged; D009185:Myelin Proteins / Q000235:genetics*; D010375:Pedigree; D010641:Phenotype; D012720:Severity of Illness Index
chemical_list: D009185:Myelin Proteins; C073687:PMP22 protein, human