Periaxin mutation causes early-onset but slow-progressive Charcot-Marie-Tooth disease

Kijima, Kazuki; Numakura, Chikahiko; Shirahata, Emi; Sawaishi, Yukio; Shimohata, Mitsuteru; Igarashi, Shuichi; Tanaka, Tomohiro; Hayasaka, Kiyoshi

doi:10.1007/s10038-004-0162-3

Cited by 47 publications

(46 citation statements)

References 16 publications

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“…Cases PRX-1, 2 and 3 Cases PRX-1, 2 and 3 had early onset symptoms but slow or no progression, and were homozygous for the R1070X mutation, as described in our previous reports (Sawaishi et al 1995;Kijima et al 2004). …”

Section: Patientsmentioning

confidence: 59%

“…Similar clinical manifestations are observed in patients carrying mutations in different genes, while variable presentations are present even in patients with an identical mutation in the same gene. Recently, there have been several reports that the periaxin (PRX) mutations were detected in the patients showing early onset of symptoms, but with slow or no progression (Boerkoel et al 2001;Guilbot et al 2001;Takashima et al 2002;Kijima et al 2004). We found heterozygous R1070X and L132fsX153 compound mutations of PRX in another patient showing early onset but no progressive clinical symptoms.…”

Section: Introductionmentioning

confidence: 59%

“…We found heterozygous R1070X and L132fsX153 compound mutations of PRX in another patient showing early onset but no progressive clinical symptoms. We further performed haplotype analysis at the PRX locus in four Japanese families, three of which had been previously reported (Kijima et al 2004). …”

Section: Introductionmentioning

confidence: 99%

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Periaxin mutation in Japanese patients with Charcot-Marie-Tooth disease

et al. 2006

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Periaxin (PRX) plays an important role in the myelination of the peripheral nerve and consequently in the pathogenesis of Charcot-Marie-Tooth disease (CMT). To date, nine nonsense or frameshift PRX mutations have been reported in eight families with CMT. The patients with PRX mutations appeared to show characteristic clinical features with early onset but slow or no progression, a common result of mutations that lead to missing a C-terminal acidic domain. Here, we report a Japanese CMT patient with these characteristic clinical features, who was a compound heterozygote for PRX R1070X and L132FsX153 mutations. We previously reported that three Japanese isolated families also had the homozygous R1070X mutation. To examine the potential founder effect of the R1070X mutation in the Japanese population, we performed haplotype analysis and found that each R1070X allele lay on a different haplotype background in these four families. Therefore, the high frequency of the R1070X mutation among the Japanese population is not likely the consequence of a founder effect, but probably a result of a mutation hot spot.

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Section: Patientsmentioning

confidence: 59%

Section: Introductionmentioning

confidence: 59%

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Periaxin mutation in Japanese patients with Charcot-Marie-Tooth disease

et al. 2006

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“…14 A number of PRX variants have been described in the literature, 6,7,9 including the variant we identified (R1070*). 8,10,11 To date the R1070* variant has been found in a number of Japanese CMT4F patients and in one Turkish patient but this is the first report of variant in a patient of Bangladeshi origin.…”

Section: Discussionmentioning

confidence: 77%

“…The mutation lies within the PRX domain of the protein and has previously been described in the literature (chr19.hg19:g.40901051; rs104894708) to cause Charcot-Marie-Tooth disease type 4 F (CMT4F) and Dejerine-Sottas disease. [6][7][8][9][10][11] Sanger sequencing confirmed the PRX mutation and showed it segregated with disease in the family in a recessive manner (Figure 1). …”

Section: Multipoint Linkage Analysis Identified Four Regions Of Linkamentioning

confidence: 94%

The use of whole-exome sequencing to disentangle complex phenotypes

Hurst

Ocaka

et al. 2015

Eur J Hum Genet

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The success of whole-exome sequencing to identify mutations causing single-gene disorders has been well documented. In contrast whole-exome sequencing has so far had limited success in the identification of variants causing more complex phenotypes that seem unlikely to be due to the disruption of a single gene. We describe a family where two male offspring of healthy first cousin parents present a complex phenotype consisting of peripheral neuropathy and bronchiectasis that has not been described previously in the literature. Due to the fact that both children had the same problems in the context of parental consanguinity we hypothesised illness resulted from either X-linked or autosomal recessive inheritance. Through the use of whole-exome sequencing we were able to simplify this complex phenotype and identified a causative mutation (p.R1070*) in the gene periaxin (PRX), a gene previously shown to cause peripheral neuropathy (Dejerine-Sottas syndrome) when this mutation is present. For the bronchiectasis phenotype we were unable to identify a causal single mutation or compound heterozygote, reflecting the heterogeneous nature of this phenotype. In conclusion, in this study we show that whole-exome sequencing has the power to disentangle complex phenotypes through the identification of causative genetic mutations for distinct clinical disorders that were previously masked.

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Charcot–Marie–Tooth Disease and Associated Peripheral Neuropathies

Espinós

2011

Encyclopedia of Life Sciences

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Charcot–Marie–Tooth (CMT) disease, a hereditary motor and sensory neuropathy, is the most frequent inherited neuromuscular disorder. According to electrophysiological and nerve biopsy criteria, CMT is classified into three categories: demyelinating, axonal and intermediate. Mutations in more than 30 genes/loci result in CMT phenotype. The main demyelinating CMT form is a 1.4‐Mb duplication, which affects the PMP22 (70%) gene, followed by mutations in the GJB1 (6%) and MPZ (3–5%) genes. Regarding axonal CMT, the commonest form is due to mutations in the MFN2 (20%) gene. Other neuropathies that share clinical similarities and genetic basis with CMT include Déjérine–Sottas syndrome, congenital hypomyelinating neuropathy and hereditary neuropathy with liability to pressure palsies. During the last decade advances have allowed to get insight of the molecular bases of this group of peripheral neuropathies and in most cases, an accurate genetic diagnosis is possible. Key Concepts: The Charcot–Marie–Tooth (CMT) disease, a hereditary motor sensory neuropathy, is the most frequent inherited neurological disease. According to electrophysiological and histopathological criteria, CMT can be classified into three forms: demyelinating, axonal and intermediate. Genes involved in Déjérine–Sottas syndrome, congenital hypomyelinating neuropathy and hereditary neuropathy with liability to pressure palsies are also associated with CMT. CMT is characterised by a wide genetic heterogeneity because more than 30 genes/loci are related to this disease and also because all the Mendelian patterns can be found in this group of diseases. The duplication of 1.4 Mb which affects the PMP22 gene (CMT1A duplication) is the most prevalent cause of Charcot–Marie–Tooth disease with a percentage of 43% of the total CMT. Once the most frequent genes related to CMT ( PMP22 , MPZ , GJB1 , MFN2 and GDAP1 ) have been ruled out, mutations in the remaining known genes occur in less than 1% of CMT cases. The complexity of CMT genetics makes difficult to identify the disease‐causing mutation in many cases and therefore, the next‐generation sequencing (NGS) technologies facilitate the genetic diagnosis.

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Periaxin mutation causes early-onset but slow-progressive Charcot-Marie-Tooth disease

Cited by 47 publications

References 16 publications

Periaxin mutation in Japanese patients with Charcot-Marie-Tooth disease

Periaxin mutation in Japanese patients with Charcot-Marie-Tooth disease

The use of whole-exome sequencing to disentangle complex phenotypes

Charcot–Marie–Tooth Disease and Associated Peripheral Neuropathies

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