title: Early onset and novel features in a spinal and bulbar muscular atrophy patient with a 68 CAG repeat.
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.
authors.affiliation: Neurogenetics Branch, National Institute of Neurological Disorders and Stroke, NIH, Bethesda, MD 20892, USA. Electronic address: christopher.grunseich@nih.gov.
authors.forename: Christopher
authors.initials: C
authors.lastname: Grunseich
authors.affiliation: Neurogenetics Branch, National Institute of Neurological Disorders and Stroke, NIH, Bethesda, MD 20892, USA.
authors.forename: Ilona R
authors.initials: IR
authors.lastname: Kats
authors.affiliation: 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.
authors.forename: Laura C
authors.initials: LC
authors.lastname: Bott
authors.affiliation: Neurogenetics Branch, National Institute of Neurological Disorders and Stroke, NIH, Bethesda, MD 20892, USA.
authors.forename: Carlo
authors.initials: C
authors.lastname: Rinaldi
authors.affiliation: Neurogenetics Branch, National Institute of Neurological Disorders and Stroke, NIH, Bethesda, MD 20892, USA.
authors.forename: Angela
authors.initials: A
authors.lastname: Kokkinis
authors.affiliation: Neurogenetics Branch, National Institute of Neurological Disorders and Stroke, NIH, Bethesda, MD 20892, USA.
authors.forename: Derrick
authors.initials: D
authors.lastname: Fox
authors.affiliation: Neurogenetics Branch, National Institute of Neurological Disorders and Stroke, NIH, Bethesda, MD 20892, USA.
authors.forename: Ke-Lian
authors.initials: KL
authors.lastname: Chen
authors.affiliation: Neurogenetics Branch, National Institute of Neurological Disorders and Stroke, NIH, Bethesda, MD 20892, USA.
authors.forename: Alice B
authors.initials: AB
authors.lastname: Schindler
authors.affiliation: Neurogenetics Branch, National Institute of Neurological Disorders and Stroke, NIH, Bethesda, MD 20892, USA.
authors.forename: Ami K
authors.initials: AK
authors.lastname: Mankodi
authors.affiliation: Rehabilitation Medicine Department, Clinical Center, NIH, Bethesda, MD 20892, USA.
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Shrader
authors.affiliation: Electromyography Section, National Institute of Neurological Disorders and Stroke, NIH, Bethesda, MD 20892, USA.
authors.forename: Daniel P
authors.initials: DP
authors.lastname: Schwartz
authors.affiliation: Electromyography Section, National Institute of Neurological Disorders and Stroke, NIH, Bethesda, MD 20892, USA.
authors.forename: Tanya J
authors.initials: TJ
authors.lastname: Lehky
authors.affiliation: Radiology and Imaging Sciences, Clinical Center, NIH, Bethesda, MD 20892, USA.
authors.forename: Chia-Ying
authors.initials: CY
authors.lastname: Liu
authors.affiliation: Neurogenetics Branch, National Institute of Neurological Disorders and Stroke, NIH, Bethesda, MD 20892, USA.
authors.forename: Kenneth H
authors.initials: KH
authors.lastname: Fischbeck
mesh_terms: D000328:Adult; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D018908:Muscle Weakness / Q000209:etiology; D020966:Muscular Disorders, Atrophic / Q000150:complications / Q000235:genetics*; D009412:Nerve Fibers / Q000473:pathology; D011944:Receptors, Androgen / Q000235:genetics*; D018911:Trinucleotide Repeats / Q000235:genetics*
chemical_list: D011944:Receptors, Androgen
keywords: Androgen receptor; Genetics; Kennedy’s disease; Motor neuron disease; Spinal bulbar muscular atrophy