Abstract
Charcot–Marie–Tooth disease is a heterogeneous group of inherited distal symmetric polyneuropathies associated with mutations in genes encoding components essential for normal functioning of the Schwann cell and axon. TRIM2, encoding a ligase that ubiquitinates the neurofilament light chain, was recently associated with early-onset neuropathy in a single patient. We report a TRIM2 homozygous missense mutation (c.2000A>C; p.D667A) in a patient with peripheral neuropathy and bilateral vocal cord paralysis, allowing for further delineation of the associated phenotypic spectrum.
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Acknowledgments
We thank the family for their participation in this study. Supported in part by the US National Human Genome Research Institute (NHGRI)/National Heart Lung and Blood Institute (NHLBI) Grant No. U54HG006542 to the Baylor-Hopkins Center for Mendelian Genomics. J.R.L. has stock ownership in 23andMe and Lasergen, Inc., is a paid consultant for Regeneron and, is a coinventor on multiple United States and European patents related to molecular diagnostics for inherited neuropathies, eye diseases, and bacterial genomic fingerprinting. The Department of Molecular and Human Genetics at Baylor College of Medicine derives revenue from the chromosomal microarray analysis and clinical exome sequencing offered in the Baylor Miraca Medical Genetics Laboratory (http://www.bcm.edu/geneticlabs/). T.H. is supported by the Medical Genetics Research Fellowship Program NIH/NIGMS NIH T32 GM07526.
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Supplementary material 1 (PDF 858 kb) Supplementary Figure 1. Absence of heterozygosity (AOH) mapping of chromosome 4. Gray shaded areas indicate AOH regions. Vertical red line indicates the location of TRIM2 which is within the ~18 Mb AOH region
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Pehlivan, D., Coban Akdemir, Z., Karaca, E. et al. Exome sequencing reveals homozygous TRIM2 mutation in a patient with early onset CMT and bilateral vocal cord paralysis. Hum Genet 134, 671–673 (2015). https://doi.org/10.1007/s00439-015-1548-3
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DOI: https://doi.org/10.1007/s00439-015-1548-3