Exome sequencing is an efficient tool for genetic screening of Charcot-Marie-Tooth disease.
Charcot-Marie-Tooth disease (CMT) is one of the most common inherited neuropathies and is a genetically and clinically heterogeneous disorder with variable inheritance modes. As several molecules have been reported to have therapeutic effects on CMT, depending on the underlying genetic causes, exact genetic diagnostics have become very important for executing personalized therapy. Whole-exome sequencing has recently been introduced as an available method to identify rare or novel genetic defects from genetic disorders. Particularly, CMT is a model disease to apply exome sequencing because more than 50 genes (loci) are involved in its development with weak genotype-phenotype correlation. This study performed the exome sequencing in 25 unrelated CMT patients who revealed neither 17p12 duplication/deletion nor several major CMT genes. This study identified eight causative heterozygous mutations (32%). This detection rate seems rather high because each sample was tested before the study for major genetic causes. Therefore, this study suggests that the exome sequencing can be a highly exact, rapid, and economical molecular diagnostic tool for CMT patients who are tested for major genetic causes.
Department of Neurology, Ewha Womans University, School of Medicine, Seoul, Korea.
Byung-Ok
BO
Choi
Soo Kyung
SK
Koo
Mi-Hyun
MH
Park
Hwanseok
H
Rhee
Song-Ju
SJ
Yang
Kyoung-Gyu
KG
Choi
Sung-Chul
SC
Jung
Han Su
HS
Kim
Young Se
YS
Hyun
Khriezhanuo
K
Nakhro
Hye Jin
HJ
Lee
Hae-Mi
HM
Woo
Ki Wha
KW
Chung
D000293:Adolescent; D000328:Adult; D000595:Amino Acid Sequence; D001483:Base Sequence; D002607:Charcot-Marie-Tooth Disease / Q000145:classification / Q000175:diagnosis* / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D004247:DNA / Q000235:genetics; D004252:DNA Mutational Analysis; D059472:Exome; D005260:Female; D005820:Genetic Testing / Q000379:methods*; D006801:Humans; D054643:INDEL Mutation; D007223:Infant; D008297:Male; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000235:genetics; D016900:Neurofilament Proteins / Q000235:genetics; D010375:Pedigree; D020641:Polymorphism, Single Nucleotide; D017386:Sequence Homology, Amino Acid; D055815:Young Adult
C118663:GDAP protein; D009419:Nerve Tissue Proteins; D016900:Neurofilament Proteins; C044882:neurofilament protein L; D004247:DNA