ABSTRACT
Charcot-Marie-Tooth disease (CMT), the most common hereditary neuropathy, has been classified into two types, demyelinating and axonal types. We previously analyzed the genes causing dominant demyelinating CMT in 227 Japanese patients to identify the genetic background, but could not find any mutations in 110 patients. To investigate the frequency of patients with autosomal recessive demyelinating CMT (CMT4) mutations, we analyzed the coding sequence of known causative genes of CMT4 in 103 demyelinating CMT patients, excluding seven patients owing to lack of specimens. We found one patient with a GDAP1 mutation, one patient with an MTMR2 mutation, two patients with SH3TC2/KIAA1985 mutations and three patients with FGD4 mutations. Twelve patients, including five previously detected patients with PRX mutations, were diagnosed as CMT4, accounting for 5.5% of demyelinating CMT. In the patient with GDAP1 mutation, only one mutation inherited from his mother was detected by genomic sequencing. Analysis by reverse transcription polymerase chain reaction using messenger RNA (mRNA) from the patient's leukocytes revealed the absence of transcription from the allele inherited from his father, suggesting the existence of one more mutation leading to a lack or destabilization of mRNA. Most patients carrying CMT4 gene mutations present with early-onset and slowly progressive symptoms, which may be associated with the function of mutants. We could not identify the disease-causing gene in 96 patients (about 45%). Further studies including studies with next-generation sequencers will be required to identify the causative gene in Japanese CMT.
Subject(s)
Charcot-Marie-Tooth Disease/genetics , Demyelinating Diseases/genetics , Genes, Recessive , Adolescent , Adult , Aged , Alternative Splicing , Child , Child, Preschool , Female , Gene Frequency , Genotype , Humans , Japan , Male , Middle Aged , Mutation , Nerve Tissue Proteins/genetics , Phenotype , Young AdultABSTRACT
PURPOSE: To report a case of cancer-associated retinopathy associated with invasive thymoma. DESIGN: Interventional case report. METHOD: A 41-year-old Japanese woman was observed between February 1998 and May 2001. Ophthalmologic examinations and systemic examinations were performed. The patient received treatment including corticosteroid pulse therapy, plasmapheresis, and thymectomy. RESULTS: The patient developed progressive visual dysfunction including bilateral visual acuity loss, concentric contraction of visual fields, and color vision loss. In both eyes, retinal vessel attenuation and retinal pigment epithelium degeneration were observed with fundus ophthalmoscopy and fluorescein angiography. Response in electroretinogram was reduced, suggesting both rod and cone dysfunction. Autoantibody against 23-kD cancer-associated retinopathy (CAR) antigen (antirecoverin antibody) was detected in the patient's serum. A mediastinal tumor that was histopathologically diagnosed as invasive thymoma was detected and was surgically resected. During more than 3 years of follow-up, no other malignancy was detected despite extensive systemic evaluation. The patient also suffered from subclinical myasthenia gravis. Although temporary improvement of visual function was observed after treatment with steroid pulse therapy and plasmapheresis' light perception of each eye was lost in the end. CONCLUSIONS: The patient was diagnosed as having CAR. Invasive thymoma was considered to be the causative tumor because there had been no evidence that suggested other systemic malignancy during more than 3 years of follow-up.
