neurogenetics

, Volume 14, Issue 1, pp 35–42

Clinical and histopathological study of Charcot-Marie-Tooth neuropathy with a novel S90W mutation in BSCL2

  • B.-O. Choi
  • M.-H. Park
  • K. W. Chung
  • H.-M. Woo
  • H. Koo
  • H.-K. Chung
  • K.-G. Choi
  • K. D. Park
  • H. J. Lee
  • Y. S. Hyun
  • S. K. Koo
Original Article

DOI: 10.1007/s10048-012-0346-5

Cite this article as:
Choi, BO., Park, MH., Chung, K.W. et al. Neurogenetics (2013) 14: 35. doi:10.1007/s10048-012-0346-5

Abstract

The objective of the study was to investigate the disease-causing mutation in an autosomal dominant Charcot-Marie-Tooth disease type 2 family and examine the clinical and histopathological evaluation. We enrolled a family of Korean origin with axonal Charcot-Marie-Tooth disease neuropathy (FC305; 13 males, six females) and applied genome-wide linkage analysis. Whole exome sequencing was performed for two patients. In addition, sural nerve biopsies were obtained from two patients. Through whole exome sequencing, we identified an average of 20,336 coding variants from two patients. We also found evidence of linkage mapped to chromosome 11p11-11q13.3 (LOD score of 3.6). Among these variants in the linkage region, we detected a novel p.S90W mutation in the Berardinelli-Seip congenital lipodystrophy 2 (BSCL2) gene, after filtering 31 Korean control exomes. Our p.S90W patients had frequent sensory disturbances, pyramidal tract signs, and predominant right thenar muscle atrophy in comparison with reported p.S90L patients. The phenotypic spectra were wide and demonstrated intrafamilial variability. Two patients with different clinical features underwent sural nerve biopsies; the myelinated fiber densities were increased slightly in both patients, which differed from two previous case reports of BSCL2 mutations (p.S90L and p.N88S). This report expands the variability of the clinical spectrum associated with the BSCL2 gene and describes the first family with the p.S90W mutation.

Keywords

Charcot-Marie-Tooth Exome sequencing Linkage analysis Mutation BSCL2 Histopathology 

Supplementary material

10048_2012_346_MOESM1_ESM.doc (40 kb)
ESM 1(DOC 40.5 kb)
10048_2012_346_MOESM2_ESM.doc (66 kb)
ESM 2(DOC 66 kb)
10048_2012_346_Fig3_ESM.jpg (45 kb)
ESM 3

(JPEG 44 kb)

10048_2012_346_MOESM3_ESM.tif (773 kb)
High Resolution ImageRight side-predominant thenar muscle atrophy in the proband (III-15). Arrow indicates the right thenar atrophy, and the arrowhead indicates left thenar atrophy (TIFF 772 kb)

Copyright information

© Springer-Verlag Berlin Heidelberg 2012

Authors and Affiliations

  • B.-O. Choi
    • 1
  • M.-H. Park
    • 2
  • K. W. Chung
    • 3
  • H.-M. Woo
    • 2
  • H. Koo
    • 4
  • H.-K. Chung
    • 1
  • K.-G. Choi
    • 1
  • K. D. Park
    • 1
  • H. J. Lee
    • 3
  • Y. S. Hyun
    • 3
  • S. K. Koo
    • 2
  1. 1.Department of NeurologyEwha Womans University School of MedicineSeoulKorea
  2. 2.Division of Intractable Diseases, Center for Biomedical SciencesNational Institute of HealthCheongwon-GunKorea
  3. 3.Department of Biological ScienceKongju National UniversityGongjuKorea
  4. 4.Department of PathologyEwha Womans University School of MedicineSeoulKorea

Personalised recommendations