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Abstract
Objective: To identify the genetic cause of an autosomal recessive demyelinating Charcot-Marie-Tooth disease type 4B (CMT4B) family.
Methods: We enrolled 14 members of a Korean family in which 3 individuals had demyelinating CMT4B phenotype and obtained distal sural nerve biopsies from all affected participants. We conducted exome sequencing on 6 samples (3 affected and 3 unaffected individuals).
Results: One pair of heterozygous missense mutations in the SET binding factor 1 (SBF1) gene (22q13.33), also called MTMR5, was identified as the underlying cause of the CMT4B family illness. Clinical phenotypes of affected study participants with CMT4B were similar, to some extent, to patients with CMT4B1 and CMT4B2. We found a similar loss of large myelinated fibers and focally folded myelin sheaths in our patients, but the actual number of myelinated fibers was different from CMT4B1 and CMT4B2.
Conclusions: We suggest that the compound heterozygous mutations in SBF1 are the underlying causes of a novel CMT4B subtype, designated as CMT4B3. We believe that this study will lead to mechanistic studies to discover the function of SBF1 and to the development of molecular diagnostics for CMT disease.
GLOSSARY
- CMAP=
- compound muscle action potential;
- CMT=
- Charcot-Marie-Tooth;
- MF=
- myelinated fiber;
- MNCV=
- motor nerve conduction velocity;
- SBF1=
- SET binding factor 1;
- siRNA=
- small interfering RNA;
- SNP=
- single nucleotide polymorphism;
- SNV=
- single nucleotide variant;
- WES=
- whole exome sequencing
Footnotes
Go to Neurology.org for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.
Supplemental data at www.neurology.org
- Received December 13, 2012.
- Accepted in final form March 19, 2013.
- © 2013 American Academy of Neurology
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- SBF1 Mutation Causes Autosomal Recessive Charcot-Marie-Tooth Disease with Microcephaly, Strabismus and Syndactyly
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