Ataxia/Episodic Ataxia Disorders (NGS Panel and Copy Number Analysis + mtDNA + SCA Repeat Expansion Analysis)

Blood | Extracted DNA

Blood: Draw blood in a lavender top EDTA tube, Sample Stability: 5-7 days, Preferred volume: 4 ml, Minimum volume: 2 ml, DO NOT FREEZE. Extracted DNA: From leukocytes, muscle, or fibroblasts: Preferred quantity: 1 microgram, Minimum quantity: 800 nanograms. Genomic DNA should be eluted in sterile Dnase/Rnase free water or TE. The A260:A280 ratio should be 1.8-2.0.

Blood: Lavender-Top (EDTA) Tube, Extracted DNA: Sterile screw capped vial

Blood: Specimens should be shipped overnight in a secure container at room temperature. Extracted DNA: Should be shipped overnight at room temperature. If previously frozen, DNA can be shipped in an insulated container with wet or dry ice.

Blood - ship ASAP, but stable up to 5 days post-collection at room temperature. DO NOT FREEZE; Swab - 60 day post-collection room temperature stability; DNA - ship at room temperature after extraction; Fibroblasts - ship flask in insulated container at room temp or refigerated; Muscle - ship in insulated container with 5-7 lbs of dry ice

Room Temperature: Blood - 5 days, Swab - 60 days, DNA - 30 days, Muscle - 0 days, Fibroblasts - 2-3 days; Refrigerated: Blood - 5 days, Swab - 60 days, DNA - 30 days, Muscle - 0 days, Fibroblasts - 2-3 days; Frozen: Blood - DO NOT FREEZE, Swab - 60 days, DNA - Indefinitely, Muscle - Indefinitely, Fibroblasts - Indefinitely; Freeze/Thaw: None

Extracted DNA A260:A280 ratio of outside of 1.8-2.0 range; Frozen blood EDTA tube; Thawed and/or fatty muscle sample; Insufficient buccal cell collection

The hereditary ataxias are a group of genetic disorders characterized by slowly progressive incoordination of gait, and often associated with poor coordination of hands, speech, and eye movements. Frequently, atrophy of the cerebellum occurs. Inherited (genetic) forms of ataxia must be distinguished from the many acquired (non-genetic) causes of ataxia. The hereditary ataxias can be inherited in an autosomal dominant (AD), autosomal recessive (AR), X-linked, or mitochondrial manner, and multiple genes are involved. Early-onset ataxias, under 20 years of age, tend to be of autosomal recessive inheritance (e.g. Friedreich’s ataxia) whereas the spinocerebellar ataxias (SCAs) are autosomal dominant and tend to present mostly after 20 years of age; although both recessive and dominant can occur at any age. The prevalence of genetic childhood ataxia varies from 0.1 to 10 cases per 100,000 people. Ataxias due to mitochondrial disease may be an under-diagnosed cause of ‘inherited’ ataxia, but the pattern of inheritance may be complex, including maternal transmission, AD and AR inheritance. The diagnosis of hereditary ataxia is based upon detection and neurologic examination of typical clinical signs and symptoms, a positive family history, and molecular analysis. Hereditary ataxias can be subdivided first by mode of inheritance, and secondarily by the gene in which the pathogenic variants occur.

Maximum reportable sizing: ATN1 – 110 repeats, ATXN1 – 150 repeats, ATXN10 – 90 repeats, ATXN2 – 150 repeats, ATXN3 – 120 repeats, ATXN7 – 125 repeats, ATXN8OS/ATXN8 – 150 repeats, CACNA1A – 145 repeats, NOP56 – 65 repeats, PPP2R2B – 150 repeats, TBP – 120 repeats

SCA1 repeat expansion testing is unable to determine if an allele greater than 40 repeats contains CAT interruptions.

Next-Generation Sequencing

SINGLE Blood Genetic Testing