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Kennedy's disease: genetic diagnosis of an inherited form of motor neuron disease
Author(s) -
Choi WT.,
MacLean H. E.,
Chu S.,
Warne G. L.,
Zajac J. D.
Publication year - 1993
Publication title -
australian and new zealand journal of medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.596
H-Index - 70
eISSN - 1445-5994
pISSN - 0004-8291
DOI - 10.1111/j.1445-5994.1993.tb01815.x
Subject(s) - spinal and bulbar muscular atrophy , motor neuron , medicine , disease , spinal muscular atrophy , asymptomatic , heterozygote advantage , lower motor neuron , androgen receptor , allele , genetics , gene , biology , prostate cancer , cancer
:Kennedy's disease (X‐linked spinal and bulbar muscular atrophy) is an inherited form of motor neuron disease that may be diagnosed genetically using the polymerase chain reaction (PCR). This form of motor neuron disease principally affects the proximal limb girdle muscles as well as those involved with deglutition and phonation. Onset is usually late, in the fourth to fifth decades of life, and progression is slow. Moderate gynecomastia and testicular atrophy are usually present, suggesting a defect in androgen receptor function. Being inherited in an X‐linked recessive manner, only males are affected, with females as the unaffected carriers. The genetic abnormality that causes Kennedy's disease is an enlargement of the androgen receptor (AR) gene, which is located on the proximal long arm of the X chromosome. In patients with this disease, a region in the gene containing repeated CAG triplet nucleotides is approximately twice the size of that found in normal people. Using PCR to amplify this region of the AR gene, this study confirms this genetic mutation in 12 males from eight different families. All these families live on the east coast of Australia. This mutation was not found in five patients with other forms of motor neuron disease. Twelve heterozygote females, the daughters of affected males and carrier females, have also been identified. In addition, there are 14 asymptomatic and as yet untested sons of carriers, ranging in age from less than one year to over 40 years of age. Each has a 50% chance of inheriting the abnormal gene from his mother and thus developing Kennedy's disease. This study shows that Kennedy's disease may be diagnosed genetically using whole blood, and discusses the ethics of prenatal and presymptomatic testing, particularly in males under 16. (Aust NZ J Med 1993; 23: 187–192.)