DOI QR코드

DOI QR Code

Association of the X-linked Androgen Receptor Leu57Gln Polymorphism with Monomelic Amyotrophy

  • Park, Young-Mi (Asan Institute for Life Sciences, Asan Medical Center) ;
  • Lim, Young-Min (Department of Neurology, University of Ulsan College of Medicine, Asan Medical Center) ;
  • Kim, Dae-Seong (Department of Neurology, Pusan National University Hospital) ;
  • Lee, Jong-Keuk (Asan Institute for Life Sciences, Asan Medical Center) ;
  • Kim, Kwang-Kuk (Department of Neurology, University of Ulsan College of Medicine, Asan Medical Center)
  • Accepted : 2011.04.11
  • Published : 2011.06.30

Abstract

Monomelic amyotrophy (MA), also known as Hirayama disease, occurs mainly in young men and manifests as weakness and wasting of the muscles of the distal upper limbs. Here, we sought to identify a genetic basis for MA. Given the predominance of MA in males, we focused on candidate neurological disease genes located on the X chromosome, selecting two X-linked candidate genes, androgen receptor (AR ) and ubiquitin-like modifier activating enzyme 1 (UBA1). Screening for genetic variants using patients' genomic DNA revealed three known genetic variants in the coding region of the AR gene: one nonsynonymous single-nucleotide polymorphism (SNP; rs78686797) encoding Leu57Gln, and two variants of polymorphic trinucleotide repeat segments that encode polyglutamine (CAG repeat; rs5902610) and polyglycine (GGC repeat; rs3138869) tracts. Notably, the Leu57Gln polymorphism was found in two patients with MA from 24 MA patients, whereas no variants were found in 142 healthy male controls. However, the numbers of CAG and GGC repeats in the AR gene were within the normal range. These data suggest that the Leu57Gln polymorphism encoded by the X-linked AR gene may contribute to the development of MA.

Keywords

References

  1. Di Guglielmo, G., Brahe, C., Di Muzio, and A., and Uncini, A. (1996). Benign monomelic amyotrophies of upper and lower limb are not associated to deletions of survival motor neuron gene. J. Neurol. Sci. 141, 111-113. https://doi.org/10.1016/0022-510X(96)00154-2
  2. Gamez, J., Also, E., Alias, L., Corbera-Bellalta, M., Barcelo, M.J., Centeno, M., Raquer, N., Gratacos, M., Baiget, M., and Tizzano, E.F. (2007). Investigation of the role of SMN1 and SMN2 haploinsufficiency as a risk factor for Hirayama's disease: clinical, neurophysiological and genetic characteristics in a Spanish series of 13 patients. Clin. Neurol. Neurosurg. 109, 844-848. https://doi.org/10.1016/j.clineuro.2007.07.019
  3. Gourie-Devi, M., and Nalini, A. (2003). Long-term follow-up of 44 patients with brachial monomelic amyotrophy. Acta. Neurol. Scand. 107, 215-220. https://doi.org/10.1034/j.1600-0404.2003.02142.x
  4. Gucuyener, K., Aysun, S., Topaloglu, H., Inan, L., and Varli, K. (1991). Monomelic amyotrophy in siblings. Pediat. Neurol. 7, 220-222. https://doi.org/10.1016/0887-8994(91)90089-4
  5. Hirayama, K. (1972). Juvenile non-progressive muscular atrophy localized in the hand and forearm: observations in 38 cases. Rinsho Shinkeigaku 12, 313-324.
  6. Hirayama, K., and Tokumaru, Y. (2000). Cervical dural sac and spinal cord in juvenile muscular atrophy of distal upper extremity. Neurology 54, 1922-1926. https://doi.org/10.1212/WNL.54.10.1922
  7. Hirayama, K., Tomonaga, M., Kitano, K., Yamada, T., Kojima, S., and Arai, K. (1987). Focal cervical poliopathy causing juvenile muscular atrophy of distal upper extremity: a pathological study. J. Neurol. Neurosurg. Psychiat. 50, 285-290. https://doi.org/10.1136/jnnp.50.3.285
  8. Hirayama, K., Toyokura, Y., and Tsubaki, T. (1959). Juvenile muscular atrophy of unilateral upper extremity: a new clinical entity. Psychiatr. Neurol. Japan. 61, 2190-2197.
  9. Jeannet, P.Y., Kuntzer, T., Deonna, T., and Roulet-Perez, E. (2005). Hirayama disease associated with a severe rhythmic movement disorder involving neck flexions. Neurology 64, 1478-1479. https://doi.org/10.1212/01.WNL.0000158678.17161.1B
  10. Kalita, J., Misra, U.K., Mishra, D.K., Thangaraj, K., Mittal, R.D., and Mittal, B.R. (2007). Nonprogressive juvenileonset spinal muscular atrophy: a clinic-radiological and CAG repeat study of androgen receptor gene. J. Neurol. Sci. 252, 24-28. https://doi.org/10.1016/j.jns.2006.09.023
  11. La Spada, A.R., Wilson, E.M., Lubahn D.B., Harding, A.E., and Fischbeck, K.H. (1991). Androgen receptor gene mutations in X-linked spinal and bulbar muscular atrophy. Nature 352, 77-79. https://doi.org/10.1038/352077a0
  12. Lee, D.K., and Chang, C. (2003). Endocrine mechanisms of disease: expression and degradation of androgen receptor: mechanism and clinical implication. J. Clin. Endocrinol. Metab. 88, 4043-4054. https://doi.org/10.1210/jc.2003-030261
  13. Lieberman, A.P., and Robins D.M. (2008). The androgen receptor's CAG/glutamine tract in mouse models of neurological disease and cancer. J. Alzheimers Dis. 14, 247-255. https://doi.org/10.3233/JAD-2008-14212
  14. McPhaul, M.J., Marcelli, M., Zoppi, S., Wilson, C.M., Griffin, J.E., and Wilson, J.D. (1992). Mutations in the ligand-binding domain of the androgen receptor gene cluster in two regions of the gene. J. Clin. Invest. 90, 2097-2101. https://doi.org/10.1172/JCI116093
  15. Misra, U.K., Kalita, J., Mishra, V.N., Kesari, A., and Mittal, B. (2005). A clinical, magnetic resonance imaging, and survival motor neuron gene deletion study of Hirayama disease. Arch. Neurol. 62, 120-123. https://doi.org/10.1001/archneur.62.1.120
  16. Misra, U.K., Kalita, J., Mishra, V.N., Phadke, R.V., and Hadique, A. (2006). Effect of neck flexion on F wave, somatosensory evoked potentials, and magnetic resonance imaging in Hirayama disease, J. Neurol. Neurosurg. Psychiatry 77, 695-698. https://doi.org/10.1136/jnnp.2005.082362
  17. Nalini, A., Lokesh, L., and Ratnavalli, E. (2004). Familial monomelic amyotrophy: a case report from India. J. Neurol. Sci. 220, 95-98. https://doi.org/10.1016/j.jns.2004.02.015
  18. Rigamonti, A., Usai, S., Curone, M., D'Amico, D., and Bussone, G. (2004). Hirayama disease: description of an Italian case. Neurol. Sci. 25, 102-103. https://doi.org/10.1007/s10072-004-0239-y
  19. Rusmini, P. Bolzoni, E., Crippa, V., Onesto, E., Sau, D., Galbiati, M., Piccolella, M., Poletti, A. (2010). Proteasomal and autophagic degradative activities in spinal and bulbar muscular atrophy. Neurobiol. Dis. 40, 361-369. https://doi.org/10.1016/j.nbd.2010.06.016
  20. Schlegel, U., Jerusalem, F., Tackmann, W., Cordt, A., and Tsuda, Y. (1987). Benign juvenile focal muscular atrophy of upper extremities: a familial case. J. Neurol. Sci. 80, 351-353. https://doi.org/10.1016/0022-510X(87)90169-9
  21. Singh, N., Sachdev, K.K., and Susheela, A.K. (1980). Juvenile muscular atrophy localized to arms. Arch. Neurol. 37, 297-299. https://doi.org/10.1001/archneur.1980.00500540075011
  22. Sobue, I., Saito, N., Iida, M., and Ando, K. (1978). Juvenile type of distal and segmental muscular atrophy of upper extremities. Ann. Neurol. 3, 429-432. https://doi.org/10.1002/ana.410030512