Genetic epidemiology of Charcot–Marie–Tooth in the general population

Braathen, Geir J.; Sand, Jette C; Lobato, Ana Christina de Lacerda; Høyer, Helle; Russell, Michael Bjørn

doi:10.1111/j.1468-1331.2010.03037.x

Cited by 144 publications

(143 citation statements)

References 36 publications

(47 reference statements)

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“…20 Our results showing complete exclusion of 17 known CMT2 disease genes in 12 unrelated Finnish families with autosomal dominant inheritance supports this hypothesis. With our population history of isolation and bottlenecks, we expect to find new disease genes with founder mutations in these families.…”

Section: Discussionsupporting

confidence: 69%

Targeted next-generation sequencing reveals further genetic heterogeneity in axonal Charcot–Marie–Tooth neuropathy and a mutation in HSPB1

et al. 2013

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Charcot-Marie-Tooth disease (CMT) is a group of hereditary peripheral neuropathies. The dominantly inherited axonal CMT2 displays striking genetic heterogeneity, with 17 presently known disease genes. The large number of candidate genes, combined with lack of genotype-phenotype correlations, has made genetic diagnosis in CMT2 time-consuming and costly. In Finland, 25% of dominant CMT2 is explained by either a GDAP1 founder mutation or private MFN2 mutations but the rest of the families have remained without molecular diagnosis. Whole-exome and genome sequencing are powerful techniques to find disease mutations for CMT patients but they require large amounts of sequencing to confidently exclude heterozygous variants in all candidate genes, and they generate a vast amount of irrelevant data for diagnostic needs. Here we tested a targeted nextgeneration sequencing approach to screen the CMT2 genes. In total, 15 unrelated patients from dominant CMT2 families from Finland, in whom MFN2 and GDAP1 mutations had been excluded, participated in the study. The targeted approach produced sufficient sequence coverage for 95% of the 309 targeted exons, the rest we excluded by Sanger sequencing. Unexpectedly, the screen revealed a disease mutation only in one family, in the HSPB1 gene. Thus, new disease genes underlie CMT2 in the remaining families, indicating further genetic heterogeneity. We conclude that targeted next-generation sequencing is an efficient tool for genetic screening in CMT2 that also aids in the selection of patients for genome-wide approaches.

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Section: Discussionsupporting

confidence: 69%

Targeted next-generation sequencing reveals further genetic heterogeneity in axonal Charcot–Marie–Tooth neuropathy and a mutation in HSPB1

et al. 2013

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“…The X-linked form of CMT (CMT1X) is the second most common form among all CMT patients with a frequency of 7-18% (average 12% internationally) (Nicolaou et al, 2010;Braathen et al, 2011). CMT1X is caused by Ͼ400 different mutations in the GJB1 gene that encodes the gap junction (GJ) protein connexin32 (Cx32).…”

Section: Introductionmentioning

confidence: 99%

The Role of Gap Junctions in Charcot-Marie-Tooth Disease

Kleopa¹

2011

J. Neurosci.

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“…Some 20 genes for axon proteins and myelin have been implicated in CMT, and allow the classification into specific subtypes of the disease. Frequently affected of these genes are peripheral myelin protein 22 (pmp22) and myelin protein zero (MPZ) which are mutated in a majority of cases (Braathen et al, 2011). CMT subtype 1A (CMT1A) is the most predominant disease type being associated with a duplication of the pmp22 gene (Wise et al, 1993;Magyar et al 1996).…”

Section: Introductionmentioning

confidence: 99%

Muscle-Targeted Gene Therapy of Charcot Marie-Tooth Disease is Dependent on Muscle Activity

Klossner¹,

Giraud²,

Oliver³

et al. 2011

Targets in Gene Therapy

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Genetic epidemiology of Charcot–Marie–Tooth in the general population

Abstract: CMT is the most common inherited neuropathy. At present, 43 CMT genes are known, and an examination of all known genes would probably only identify mutations in approximately 50% of those with CMT. Thus, it is probable that at least 30-50 CMT genes are yet to be identified.

Cited by 144 publications

References 36 publications

Targeted next-generation sequencing reveals further genetic heterogeneity in axonal Charcot–Marie–Tooth neuropathy and a mutation in HSPB1

Targeted next-generation sequencing reveals further genetic heterogeneity in axonal Charcot–Marie–Tooth neuropathy and a mutation in HSPB1

The Role of Gap Junctions in Charcot-Marie-Tooth Disease

Muscle-Targeted Gene Therapy of Charcot Marie-Tooth Disease is Dependent on Muscle Activity

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