Jan 22, 2011

Exome sequencing allows for rapid gene identification in a Charcot-Marie-Tooth family

Annals of Neurology
Gladys MontenegroStephan Züchner


Charcot-Marie-Tooth (CMT) disease comprises a large number of genetically distinct forms of inherited peripheral neuropathies. The relative uniform phenotypes in many patients with CMT make it difficult to decide which of the over 35 known CMT genes are affected in a given patient. Genetic testing decision trees are therefore broadly based on a small number of major subtypes (eg, CMT1, CMT2) and the observed mutation frequency for CMT genes. Since conventional genetic testing is expensive many rare genes are not being tested for at all. Whole-exome sequencing has recently been introduced as a novel and alternative approach. This method is capable of resequencing a nearly complete set of coding exons in an individual. We performed whole-exome sequencing in an undiagnosed family with CMT. Within over 24,000 variants detected in 2 exomes of a CMT family, we identified a nonsynonymous GJB1 (Cx32) mutation. This variant had been reported previously as pathogenic in X-linked CMT families. Sanger sequencing confirmed complete cosegregation in the family. Affected individuals had a marked early involvement of the upper distal extremities and displayed a mild reduction of nerve conduction velocities. We have shown for the first time in ...Continue Reading

Mentioned in this Paper

GJB1 gene
Charcot-Marie-Tooth Disease
Pathogenic Organism
Genetic Screening Method
Inherited Peripheral Neuropathy
Limb Structure
DNA Resequencing

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