Early onset and novel features in a spinal and bulbar muscular atrophy patient with a 68 CAG repeat

doi:10.1016/j.nmd.2014.06.441

Case Reports

. 2014 Nov;24(11):978-81.

doi: 10.1016/j.nmd.2014.06.441. Epub 2014 Jul 3.

Early onset and novel features in a spinal and bulbar muscular atrophy patient with a 68 CAG repeat

Affiliations

¹ Neurogenetics Branch, National Institute of Neurological Disorders and Stroke, NIH, Bethesda, MD 20892, USA. Electronic address: christopher.grunseich@nih.gov.
² Neurogenetics Branch, National Institute of Neurological Disorders and Stroke, NIH, Bethesda, MD 20892, USA.
³ Neurogenetics Branch, National Institute of Neurological Disorders and Stroke, NIH, Bethesda, MD 20892, USA; Department of Cell and Molecular Biology, Karolinska Institute, 17177 Stockholm, Sweden.
⁴ Rehabilitation Medicine Department, Clinical Center, NIH, Bethesda, MD 20892, USA.
⁵ Electromyography Section, National Institute of Neurological Disorders and Stroke, NIH, Bethesda, MD 20892, USA.
⁶ Radiology and Imaging Sciences, Clinical Center, NIH, Bethesda, MD 20892, USA.

PMID: 25047668
PMCID: PMC4252652
DOI: 10.1016/j.nmd.2014.06.441

Case Reports

Early onset and novel features in a spinal and bulbar muscular atrophy patient with a 68 CAG repeat

Christopher Grunseich et al. Neuromuscul Disord. 2014 Nov.

. 2014 Nov;24(11):978-81.

doi: 10.1016/j.nmd.2014.06.441. Epub 2014 Jul 3.

Affiliations

¹ Neurogenetics Branch, National Institute of Neurological Disorders and Stroke, NIH, Bethesda, MD 20892, USA. Electronic address: christopher.grunseich@nih.gov.
² Neurogenetics Branch, National Institute of Neurological Disorders and Stroke, NIH, Bethesda, MD 20892, USA.
³ Neurogenetics Branch, National Institute of Neurological Disorders and Stroke, NIH, Bethesda, MD 20892, USA; Department of Cell and Molecular Biology, Karolinska Institute, 17177 Stockholm, Sweden.
⁴ Rehabilitation Medicine Department, Clinical Center, NIH, Bethesda, MD 20892, USA.
⁵ Electromyography Section, National Institute of Neurological Disorders and Stroke, NIH, Bethesda, MD 20892, USA.
⁶ Radiology and Imaging Sciences, Clinical Center, NIH, Bethesda, MD 20892, USA.

PMID: 25047668
PMCID: PMC4252652
DOI: 10.1016/j.nmd.2014.06.441

Abstract

Spinal and bulbar muscular atrophy (SBMA) is an X-linked neuromuscular disease caused by a trinucleotide (CAG) repeat expansion in the androgen receptor gene. Patients with SBMA have weakness, atrophy, and fasciculations in the bulbar and extremity muscles. Individuals with CAG repeat lengths greater than 62 have not previously been reported. We evaluated a 29year old SBMA patient with 68 CAGs who had unusually early onset and findings not seen in others with the disease. Analysis of the androgen receptor gene confirmed the repeat length of 68 CAGs in both peripheral blood and fibroblasts. Evaluation of muscle and sensory function showed deficits typical of SBMA, and in addition the patient had manifestations of autonomic dysfunction and abnormal sexual development. These findings extend the known phenotype associated with SBMA and shed new insight into the effects of the mutated androgen receptor.

Keywords: Androgen receptor; Genetics; Kennedy’s disease; Motor neuron disease; Spinal bulbar muscular atrophy.

Published by Elsevier B.V.

PubMed Disclaimer

Figures

**Figure 1. Strength testing and muscle MRI findings**
Quantitative muscle strength testing in 12 different muscle groups shows the degree of muscle weakness (in kg) as compared to healthy controls matched for age, height, weight, and body side (A). STIR MRI image of the right thigh showing patchy areas of hyperintensity indicative of muscle injury and degeneration (B). T1 image of the same region shows muscle atrophy and evidence of increased fat signal within the muscle (C).

**Figure 2. Androgen receptor gene and protein**
PCR products from patient DNA were generated using primers that bracket the CAG expansion. Acrylamide gel electrophoresis shows the band shift relative to a 62 CAG sample from a different patient (A). Androgen receptor expression is equal in patient derived fibroblast cultures when compared to control samples on western blotting. Dihydrotestosterone (DHT) treatment results in similar upregulation of androgen receptor levels in all samples evaluated (B).

See this image and copyright information in PMC

Cited by

The metabolic and endocrine characteristics in spinal and bulbar muscular atrophy.
Rosenbohm A, Hirsch S, Volk AE, Grehl T, Grosskreutz J, Hanisch F, Herrmann A, Kollewe K, Kress W, Meyer T, Petri S, Prudlo J, Wessig C, Müller HP, Dreyhaupt J, Weishaupt J, Kubisch C, Kassubek J, Weydt P, Ludolph AC. Rosenbohm A, et al. J Neurol. 2018 May;265(5):1026-1036. doi: 10.1007/s00415-018-8790-2. Epub 2018 Feb 20. J Neurol. 2018. PMID: 29464380
Human adipose-derived mesenchymal stem cells as a new model of spinal and bulbar muscular atrophy.
Dossena M, Bedini G, Rusmini P, Giorgetti E, Canazza A, Tosetti V, Salsano E, Sagnelli A, Mariotti C, Gellera C, Navone SE, Marfia G, Alessandri G, Corsi F, Parati EA, Pareyson D, Poletti A. Dossena M, et al. PLoS One. 2014 Nov 13;9(11):e112746. doi: 10.1371/journal.pone.0112746. eCollection 2014. PLoS One. 2014. PMID: 25392924 Free PMC article.
Non-neural phenotype of spinal and bulbar muscular atrophy: results from a large cohort of Italian patients.
Querin G, Bertolin C, Da Re E, Volpe M, Zara G, Pegoraro E, Caretta N, Foresta C, Silvano M, Corrado D, Iafrate M, Angelini L, Sartori L, Pennuto M, Gaiani A, Bello L, Semplicini C, Pareyson D, Silani V, Ermani M, Ferlin A, Sorarù G; Italian Study Group on Kennedy's disease. Querin G, et al. J Neurol Neurosurg Psychiatry. 2016 Aug;87(8):810-6. doi: 10.1136/jnnp-2015-311305. Epub 2015 Oct 26. J Neurol Neurosurg Psychiatry. 2016. PMID: 26503015 Free PMC article.
A Crucial Role for the Protein Quality Control System in Motor Neuron Diseases.
Cristofani R, Crippa V, Cicardi ME, Tedesco B, Ferrari V, Chierichetti M, Casarotto E, Piccolella M, Messi E, Galbiati M, Rusmini P, Poletti A. Cristofani R, et al. Front Aging Neurosci. 2020 Jul 21;12:191. doi: 10.3389/fnagi.2020.00191. eCollection 2020. Front Aging Neurosci. 2020. PMID: 32792938 Free PMC article.
X-linked spinal and bulbar muscular atrophy (Kennedy's disease): the first case described in the Brazilian Amazon.
Alves CN, Braga TKK, Somensi DN, Nascimento BSVD, Lima JAS, Fujihara S. Alves CN, et al. Einstein (Sao Paulo). 2018 Jun 7;16(2):eRC4011. doi: 10.1590/S1679-45082018RC4011. Einstein (Sao Paulo). 2018. PMID: 29898093 Free PMC article.

See all "Cited by" articles

References

1. Kennedy WR, Alter M, Sung JH. Progressive proximal spinal and bulbar muscular atrophy of late onset: a sex-linked recessive trait. Neurology. 1968;18:671–680. - PubMed
1. Grunseich C, Rinaldi C, Fischbeck KH. Spinal and bulbar muscular atrophy: pathogenesis and clinical management. Oral Dis. 2014;20:6–9. - PMC - PubMed
1. Walcott JL, Merry DE. Ligand promotes intranuclear inclusions in a novel cell model of spinal and bulbar muscular atrophy. J Biol Chem. 2002;277:50855–50859. - PubMed
1. Li M, Miwa S, Kobayashi Y, et al. Nuclear inclusions of the androgen receptor protein in spinal and bulbar muscular atrophy. Ann Neurol. 1998;44:249–254. - PubMed
1. McCampbell A, Taylor JP, Taye AA, et al. CREB-binding protein sequestration by expanded polyglutamine. Hum Molec Genet. 2000;9:2197–2202. - PubMed

Publication types

Actions

MeSH terms

Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions

Substances

Actions

Grants and funding

Z99 NS999999/Intramural NIH HHS/United States

LinkOut - more resources

Full Text Sources
Other Literature Sources
- scite Smart Citations

[1] Kennedy WR, Alter M, Sung JH. Progressive proximal spinal and bulbar muscular atrophy of late onset: a sex-linked recessive trait. Neurology. 1968;18:671–680. - PubMed

[2] Kennedy WR, Alter M, Sung JH. Progressive proximal spinal and bulbar muscular atrophy of late onset: a sex-linked recessive trait. Neurology. 1968;18:671–680. - PubMed

[3] Grunseich C, Rinaldi C, Fischbeck KH. Spinal and bulbar muscular atrophy: pathogenesis and clinical management. Oral Dis. 2014;20:6–9. - PMC - PubMed

[4] Grunseich C, Rinaldi C, Fischbeck KH. Spinal and bulbar muscular atrophy: pathogenesis and clinical management. Oral Dis. 2014;20:6–9. - PMC - PubMed

[5] Walcott JL, Merry DE. Ligand promotes intranuclear inclusions in a novel cell model of spinal and bulbar muscular atrophy. J Biol Chem. 2002;277:50855–50859. - PubMed

[6] Walcott JL, Merry DE. Ligand promotes intranuclear inclusions in a novel cell model of spinal and bulbar muscular atrophy. J Biol Chem. 2002;277:50855–50859. - PubMed

[7] Li M, Miwa S, Kobayashi Y, et al. Nuclear inclusions of the androgen receptor protein in spinal and bulbar muscular atrophy. Ann Neurol. 1998;44:249–254. - PubMed

[8] Li M, Miwa S, Kobayashi Y, et al. Nuclear inclusions of the androgen receptor protein in spinal and bulbar muscular atrophy. Ann Neurol. 1998;44:249–254. - PubMed

[9] McCampbell A, Taylor JP, Taye AA, et al. CREB-binding protein sequestration by expanded polyglutamine. Hum Molec Genet. 2000;9:2197–2202. - PubMed

[10] McCampbell A, Taylor JP, Taye AA, et al. CREB-binding protein sequestration by expanded polyglutamine. Hum Molec Genet. 2000;9:2197–2202. - PubMed

Save citation to file

Email citation

Add to Collections

Add to My Bibliography

Your saved search

Create a file for external citation management software

Your RSS Feed

Early onset and novel features in a spinal and bulbar muscular atrophy patient with a 68 CAG repeat

Affiliations

Early onset and novel features in a spinal and bulbar muscular atrophy patient with a 68 CAG repeat

Authors

Affiliations

Abstract

Figures

Similar articles

Cited by

References

Publication types

MeSH terms

Substances

Grants and funding

LinkOut - more resources

Full Text Sources

Other Literature Sources

Abstract

Figures

Similar articles

Cited by

References

Publication types

MeSH terms

Substances

Related information

Grants and funding

LinkOut - more resources

Full Text Sources

Other Literature Sources