Genetics of Ataxia

Many forms of ataxia are due to inheritance of a gene that carries a mutation. A gene is the cell's instructions for making a specific protein. In some cases, the mutation causes the protein not to be made at all, or to be useless (a "loss-of-function" mutation). In other cases, the mutation causes the protein to take on some new function which is bad for the cell (a "toxic-gain-of-function" mutation).

The chart shows the known genetic forms of ataxia, the name of the mutated gene and its protein product, and important clinical features. It also indicates the pattern of inheritance (see "Inheritance Patterns" on the next page), where the gene is located on the chromosomes (locus), the type of mutation, and whether genetic testing is available.

The number of recognized genetic ataxias has grown considerably due to advances in gene discovery methods. Most forms are quite rare.

designation	gene/gene product	mean age at onset	prominent features	inheritance	locus	mutation	genetic testing available	comments
SCA1	ATXN1/ataxin-1	4th decade	Bulbar, corticospinal, extrapyramidal signs	AD	6p23	CAG repeat	yes	6% of all AD cerebellar ataxia
SCA2	ATXN2/ataxin-2	4th decade	slow saccades, neuropathy, dementia	AD	12q24	CAG repeat	yes	13% of all AD cerebellar ataxia
SCA3 Machado-Joseph disease	ATXN3/ataxin-3; MJD protein 1	4th decade	bulging eyes, facial fasciculations		14q24.3-q31	CAG repeat	yes	23% of all AD cerebellar ataxia
SCA4	Q9H7K4/puratrophin-1		sensory neuropathy		16q22.1		yes
SCA5	SPTBN2/spectrin beta chain, brain 2	4th decade			11q13		yes
SCA6	CACNA1A/voltage-dependent P/Q-type calcium channel alpha-1A subunit	6th decade			19p13	CAG repeat	yes
SCA7	ATXN7/ataxin-7	4th decade			3p21.1-p12	CAG repeat	yes
SCA8	KLHL1AS	5th decade			13q21		yes
SCA9
SCA10	ATXN10/ataxin-10; E46L	4th decade	isolated ataxia		22q13		yes
SCA11		3rd decade			15q14-q21.3
SCA12	PPP2R2B/brain-specific regulatory subunit of protein phosphatase 2A	4th decade			5q31-q33		yes
SCA13		Childhood			19q13.3-q13.4
SCA14	PRKCG/protein kinase C, gamma subtype	3rd decade			19q13.4		yes
SCA15		3rd decade			3p26.1-p25.3
SCA16		5th decade			8q22.1-q24.1
SCA17	TBP/TATA-box binding protein	4th decade			6q27		yes
SCA18		2nd decade			7q22-q32
SCA19		4th decade			1p21-q21
SCA20		5th decade			11p13-q11
SCA21		2nd decade			7p21.3-p15.1
SCA22					1p21-q21
SCA23					20p13-p12.3
SCA24
SCA25					2p21-p13
SCA26					19p13.3
SCA27	FGF14/fibroblast growth factor 14	2nd decade			13q34		yes
SCA28					18p11.22-q11.2
Friedreich's ataxia	frataxin	mainly childhood, but 25% adult	Areflexia, pes cavus, cardiomyopathy	AR		GAA repeat
DRPLA	DRPLA/atrophin1-related protein	4th decade	Chorea, myoclonus, seizures, dementia		12p13.31	CAG repeat	yes
EA1	KCNA1/potassium voltage-gated channel component		episodic ataxia, myokymia		12p13		yes
EA2	CACNA1A/voltage-dependent P/Q-type calcium channel alpha-1A subunit		episodic ataxia		19p13
FXTAS	FMR-1		tremor, ataxia	X-linked	Xq27.3	CGG repeat		usually male relatives of boys with fragile X syndrome

SCA=spinocerebellar ataxia; DRPLA=dentatorubral pallidoluysian atrophy; EA=episodic ataxia; FXTAS=fragile X-associated tremor ataxia syndrome; AD=autosomal dominant; AR=autosomal recessive

	Inheritance Patterns