Tottori J. Clin. Res. 9(2), 190-204, 2017

An autopsy case of the Kennedy-Alter-Sung type offamilial spinal and bulbar muscular atrophy:
Demonstration of a CAG repeat in the androgen receptor geneusing whole genome amplification
Yoshihiro Konishi1)* Kiho Araki1) Ichiko Yoshida1) Kaori Morimoto1) Yumako Miura1)
Yasumasa Monobe2) Yuko Saito3) Ikuko Aiba3) Hirotake Nishimura4)
1) Department of Clinical Research, NHO Tottori Medical Center2) Department of Pathology, Kawasaki Hospital, Kawasaki Medical School3) Department of Neurology, NHO Higashi-Nagoya Hospital4) Department of Pathology 1, Kawasaki Medical School*Correspondence: ykonishi@tottori-iryo.hosp.go.jp
Abstract
Spinal and bulbar muscular atrophy (SBMA) is an X-linked recessive trinucleotide, polyglutamine (polyQ)
disease, caused by the abnormal expansion of a polymorphic CAG tandem-repeat in the first exon of theandrogen receptor (AR) gene. SBMA was first reported by Kennedy, Alter, and Sung; therefore, this disease isoften referred to as Kennedy-Alter-Sung syndrome. Spada, Fischbeck, and colleagues discovered SBMA iscaused by an unstable CAG repeat expansion in the first exon of the AR gene. Thereafter, the complete
diagnosis of SBMA is generally made possible by genetic analysis of patient-derived tissues or peripheral bloodcells; however, when an extremely insufficient amount of unfixed biopsy tissue or postmortem tissue isavailable, genetic analysis by the standard PCR method reported by Spada, Fischbeck, and colleagues may beimpossible. To address this issue, whole genome amplification (WGA) technology was applied. With thistechnology, we have verified successfully the expansion of a polymorphic CAG tandem-repeat in the first exonof the AR gene, using a trace amount of genomic DNA. This DNA originated from only two sections of unfixed,unstained muscle tissue specimens obtained by biopsy from a patient 24 years prior. The muscle tissue
specimens had been subjected to long-term storage at room temperature (RT). They were of 10 micrometer
thickness weighing 1–2 mg, and were the only tissue samples available for genetic analysis at that time. Forcomparison, frozen postmortem brain tissues obtained from another patient with SBMA were processed in asimilar manner. Tottori J. Clin. Res. 9(2), 190-204, 2017
Key words: spinal and bulbar muscular atrophy (SBMA), Kennedy-Alter-Sung (KAS) syndrome, androgen
receptor (AR), CAG repeat, polyglutamine (polyQ), whole genome amplification (WGA)
Introduction
SBMA is an adult-onset (third to fifth decadeof life), X-linked recessive trinucleotide, polyQ
disease, caused by the abnormal expansion of apolymorphic CAG tandem-repeat in the firstexon of the AR gene, which is mapped tochromosome Xq11-q12. This disorder was firstreported by Kennedy, Alter, and Sung1) in 1968;
therefore, this disease is often called

Kennedy-Alter-Sung syndrome (also known as
Kennedy’s disease). SBMA is characterized by
the following: proximal limb, facial, masseter,
and bulbar muscular atrophy, weakness withcontraction fasciculation, fine finger tremor,
muscle cramps, hoarseness, rhinolalia aperta,
dysphagia, dysarthria, diminished deep tendon
reflex without pathological reflex, and an
impaired sense of vibration2). The muscle weakn-