Androgen receptor gene (CAG)n repeat analysis in the differential diagnosis between Kennedy disease and other motoneuron disorders

Abstract

An increase in the number of (CAG)n repeats in the first coding exon of the androgen receptor (AR) gene has been strongly associated with Kennedy disease (KD) (spinal and bulbar muscular atrophy). This is an X-linked hereditary disorder characterized by motoneuron degeneration occurring in adults together with gynecomastia and hyperestrogenemia. We have performed AR gene molecular analysis in several members of a large family with KD as well as in 25 sporadic patients suffering from heterogeneous motoneuron disease (MND). An increase in the length of the (CAG)n repeats was detected, as expected, in all the affected males and in obligatory carrier females, some of which had minor signs of lower motoneuron involvement. There was only one possible exception, one young male with initial signs of the disease, who had an apparent normal length allele. An increased pathological allele was also found in 3 patients with MND. This indicates that the analysis of (CAG)n repeats of the AR gene plays a role in the differential diagnosis of this heterogeneous group of neurological diseases.

Castration Restores Function and Neurofilament Alterations of Aged Symptomatic Males in a Transgenic Mouse Model of Spinal and Bulbar Muscular Atrophy

“…Despite this dominant toxic property, women rarely show symptoms of the disease, although some mild cases have been reported (Ferlini et al, 1995).…”

Atrofia muscular bulbo espinhal recessiva ligada ao cromossomo X (doença de Kennedy): estudo de uma família

“…Esses achados indicam que a análise por PCR do gene do receptor androgênico dos trinucleotídeos repetidos desempenha um papel preciso no diagnóstico diferencial entre doença de Kennedy e outras síndromes clinicamente similares neste grupo heterogêneo de doenças neurológicas 16,17 . Do ponto de vista clínico, nossos três pacientes são típicos de doença de Kennedy.…”

Molecular Analysis of the Androgen Receptor Gene in Kennedy’s Disease

“…In our experience, the diagnosis of SBMA was suspected in several patients but was then ruled out by molecular analysis showing normal CAG number. Recently, Jobsis et al [20] and Ferlini et al [21] showed the role now played by the analysis of (CAG)n repeats of the AR gene in the differential diagnosis of Kennedy's dis ease among motoneuron diseases.…”