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Paediatric Laboratory Medicine

Spinal and Bulbar Muscular Atrophy: AR Trinucleotide Repeat Analysis

Clinical Significance

Spinal and bulbar muscular atrophy (SBMA or Kennedy disease) is an X-linked recessive motor neuron disease that occurs in one in 50,000 males. It is characterized by slowly progressive muscle weakness associated with mild insensitivity to the hormone androgen. Symptoms typically begin between the ages of 20 and 50 years with difficulty walking and a tendency to fall. Some patients have muscle cramps, while others complain of action tremors. Patients often show breast development, testicular atrophy and reduced fertility due to androgen insensitivity. The vast majority of patients with SBMA have a normal life expectancy and do not die from direct complications of their disease.

The principal mutation causing SBMA is an increase in the number of CAG repeats within the androgen receptor (AR) gene located on the X chromosome (specifically Xq11-q12). The normal gene contains a three base pair sequence that is repeated on each X chromosome (called a CAG trinucleotide repeat). Although variable in the general population, the number of repeats is usually inherited without change from generation to generation. In unaffected individuals, this region ranges in size from 9 to 34 repeats, whereas individuals affected with SBMA have 36-66 repeats (full mutation).

Males normally have one X chromosome in each cell. If that X chromosome carries the expansion mutation in the AR gene, the boy will have SBMA. Affected males who are fertile pass the expanded gene to each daughter. As a result, all daughters of affected fathers are carriers. Males do not pass an X chromosome to their sons. As a result, the sons of affected fathers do not receive the expanded gene, and are not affected. Females normally have two X chromosomes in each cell. If one X chromosome carries the mutation in the AR gene and the other one does not, the girl will be a carrier of SBMA. Carriers do not have and will not develop SBMA. Carrier females may, however, transmit the repeat expansion in the AR gene to their children. Each son of a carrier mother has a 50 per cent risk of being affected. Each daughter of a carrier mother has a 50 per cent risk of being a carrier.

Test Name

Spinal and Bulbar Muscular Atrophy: AR Trinucleotide Repeat Analysis

Alternate Name/ Synonym

  • SBMA
  • Kennedy's disease

Gene Name

  • AR

Test Code

SBMA

Division

Molecular Genetics

Method

AR exon 1 trinucleotide (CAG) repeat analysis

External Proficiency Testing

CAP

Turn Around Time

2 weeks (Prenatal samples), 2-3 weeks (Pregnancy/Urgent samples), 4-6 weeks (Routine)

Protein

Androgen receptor

Disease/Condition

Spinal and Bulbar Muscular Atrophy

Specimen Type

Blood; gDNA.

For details about specimen requirements, please refer to: Specimen Type & Requirements (PDF).

Minimum Specimen Requirements

5-10 mL EDTA or ACD, 0.5 mL EDTA (neonate); minimum 10 ug in 100 uL low TE (pH8.0)

Storage/Transportation

Room Temperature

Special Requirements

Special Instructions for Genome Diagnostics Samples

If sample shipment >48 hours, ship on ice.

Approval is not required

CPT Codes

81401

Shipping and Contact Information

The Hospital for Sick Children
Rapid Response Laboratory
170 Elizabeth Street, Room 3642
Toronto, ON
M5G 2G3
Canada
Phone: 416-813-7200
Phone: 1-855-381-3212

Interpretation

Interpretation is provided in report