Copy number variations are a rare cause of non-CMT1A Charcot-Marie-Tooth disease

Huang, Jian; Wu, Xingyao; Montenegro, Gladys; Price, Justin; Wang, Gaofeng; Vance, Jeffery M.; Shy, Michael E.; Züchner, Stephan

doi:10.1007/s00415-009-5401-2

Cited by 22 publications

(18 citation statements)

References 18 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, we did not find any quantitative alteration in major-causative genes other than PMP22 by MLPA analysis. Huang et al 34 did not find any copy number variation in CMT-causing genes other than PMP22 on comparative genomic hybridization microarrays. This suggests that quantitative alteration of disease-causing genes other than PMP22 is not likely a major cause of CMT.…”

Section: Discussionmentioning

confidence: 95%

Molecular diagnosis and clinical onset of Charcot–Marie–Tooth disease in Japan

et al. 2011

View full text Add to dashboard Cite

To study the genetic background of Japanese Charcot-Marie-Tooth disease (CMT) patients, we analyzed qualitative and quantitative changes in the disease-causing genes mainly by denaturing high performance liquid chromatography and multiplex ligation-dependent probe analysis in 227 patients with demyelinating CMT and 127 patients with axonal CMT. In demyelinating CMT, we identified 53 patients with PMP22 duplication, 10 patients with PMP22 mutations, 20 patients with MPZ mutations, eight patients with NEFL mutations, 19 patients with GJB1 mutations, one patient with EGR2 mutation, five patients with PRX mutations and no mutations in 111 patients. In axonal CMT, we found 14 patients with MFN2 mutations, one patient with GARS mutation, five patients with MPZ mutations, one patient with GDAP1 mutation, six patients with GJB1 mutations and no mutations in 100 patients. Most of the patients carrying PMP22, MPZ, NEFL, PRX and MFN2 mutations showed early onset, whereas half of the patients carrying PMP22 duplication and all patients with GJB1 or MPZ mutations showing axonal phenotype were adult onset. Our data showed that a low prevalence of PMP22 duplication and high frequency of an unknown cause are features of Japanese CMT. Low prevalence of PMP22 duplication is likely associated with the mild symptoms due to genetic and/or epigenetic modifying factors.

show abstract

Section: Discussionmentioning

confidence: 95%

Molecular diagnosis and clinical onset of Charcot–Marie–Tooth disease in Japan

et al. 2011

View full text Add to dashboard Cite

show abstract

“…6 However, CNVs of other neuropathy genes are rarely reported. 7 In this article, we describe a family with an intragenic duplication CNV in one of the autosomal-recessive (AR)–CMT genes, NDRG1 , with three affected individuals born to consanguineous parents from a first-degree cousin marriage. To the best of our knowledge, this is the first report of AR duplication CNV causing a CMT disease phenotype and only the third mutation reported in the NDRG1 gene.…”

Section: Introductionmentioning

confidence: 99%

Exonic duplication CNV of NDRG1 associated with autosomal-recessive HMSN-Lom/CMT4D

Okamoto

Goksungur

Pehlivan

et al. 2014

Genetics in Medicine

View full text Add to dashboard Cite

Purpose Copy-number variations as a mutational mechanism contribute significantly to human disease. Approximately one-half of the patients with Charcot–Marie–Tooth (CMT) disease have a 1.4 Mb duplication copy-number variation as the cause of their neuropathy. However, non-CMT1A neuropathy patients rarely have causative copy-number variations, and to date, autosomal-recessive CMT disease has not been associated with copy-number variation as a mutational mechanism. Methods We performed Agilent 8 × 60K array comparative genomic hybridization on DNA from 12 recessive Turkish families with CMT disease. Additional molecular studies were conducted to detect breakpoint junctions and to evaluate gene expression levels in a family in which we detected an intragenic duplication copy-number variation. Results We detected an ~6.25 kb homozygous intragenic duplication in NDRG1, a gene known to be causative for recessive HMSNL/CMT4D, in three individuals from a Turkish family with CMT neuropathy. Further studies showed that this intragenic copy-number variation resulted in a homozygous duplication of exons 6–8 that caused decreased mRNA expression of NDRG1. Conclusion Exon-focused high-resolution array comparative genomic hybridization enables the detection of copy-number variation carrier states in recessive genes, particularly small copy-number variations encompassing or disrupting single genes. In families for whom a molecular diagnosis has not been elucidated by conventional clinical assays, an assessment for copy-number variations in known CMT genes might be considered.

show abstract

“…However, CMT has been associated with mutations in over 35 genes. Occurrence of CNV in other forms of CMT was investigated by Huang and co-workers [8]. The study cohort included 97 patients and the analysis consisted of a custom CGH microarray for 34 genomic regions harbouring known genes for CMT.…”

Section: Genotypic Analysis Of Congenital Myasthenic Syndromementioning

confidence: 99%