Table 3.

SACS mutations discovered in Asia. “hm” means mutation carried the homozygous form, “c het” means mutation had compound heterozygous allele. “rs” means respectively.

Mutation	Exon	Domain	AOO	Clinical Symptoms	Neurological Changes	Country (Ethnicity)	References
p.3774C>T, p.Q1198X, c.het	10	XPCB & SIRPT1, rs	9 yrs	spastic gait in at 9 yrs old in her 30s, unsteadiness in gait hand clumsiness pes cavus optokinetic nystagmus	vermian atrophy in pyramidal system	Japan (Japanese)	[78]
c.2951_2952delAG(p.Q984GfsX986)+3922delT(p.1308LfsX1326), c. het	10	SIRPT1 + between SIRPT3 & XPBC, rs	15–20 yrs	gait & speech dysfunctions nystagmus pes caves cerebellar ataxia	atrophy in cerebellum cervical & thoracic cord progressive neuropathy, no hypermyelinated retinal fibers		[81]
c.32627-32636delACACTGTTAC(p.W395-fsX407), c.31760delT (p.V687-fsX713), c.het	8	SIRPT1	under 10 yrs	spasticity weakness in lower extremities limb & truncal ataxia pes caves pes vares	cerebellar atrophy (upper vermis) no retinal hypermyelination		[79]
c.6543delA, (p.R2002X), hm	10	SIRPT2	early childhood	spastic tetraplegia weakness & amyotrophy in limbs nystagmus ataxic speech pes cavus dementia	atrophy in superior vermis & thin corpus callosum no retinal myelinated fibers		[80]
c.5988-9del CT, hm	10	SIRPT2	early childhood	limb & truncal ataxia gait slurred speech limb deformities initial leg spasticity disappeared	cerebellar superior vermian atrophy decreased blood flow in cerebellum neuropathies hypermyelinated fibers in retinal optic nerve		[81]
c. 987C>T (p.F304S), hm	8	SIRPT1	before 10 yrs	gait in childhood worsened in their 20s no spasticity mild limb ataxia slurred speech	cerebellar atrophy myelinated retinal fibers		[82]
c. 6355C>T (p.R2119X), hm	10	SIRPT2	20s	nystagmus, ataxic speech truncal & limb ataxia limb deformities but no spasticity	cerebellar atrophy atrophy in mega cisterna magna & cervical cord, but not in cervical cord no retinal optic nerve hypermyelination		[83]
c.482delA (p.L802P), c.2405T>C (p.N161fsX175), c-het	10 & 7 rs	SIRPT1	late 10s- early 20s	mental retardation gait & speech disturbance nystagmus pes cavus no spasticity	progressive peripheral neuropathy cerebellar & cervical cord atrophy no myelinated retinal fibers		[85]
c.12976A/G (p.K4326Q), c.4233-4236 delACTT (p.L1412Kfs*16), c-het	10	DNAJ + SIRPT2, rs	~22 yrs	progressive gait disturbances saccadic eye movement nystagmus scanning speech cerebellar ataxia no spasticity	atrophy in cerebellar & cervical spinal cord area polyneuropathy no myelinated retinal fibers		[85]
c.3769 G>T (p.G1257X)+11361–2insT(p.R3788SfsX3820), c-het	10	SIRPT2 & SIRPT3, rs	12 yrs	cerebellar ataxia hyperreflexia, spasticity	cerebellar atrophy neuropathy myelinated retinal fibers		[86]
c.414 C>G (p.Y138X) +5263–4delAA (p.K1755VfsX1775), c-het	7 & 10, rs	SIRPT1 & SIRPT2, rs	12–19 yrs	cerebellar ataxia hyperreflexia spasticity unstable gait foot deformities stiffness spasticity in lower extremities ataxia in upper extremities muscle atrophy	cerebellar atrophy cervical cord atrophy spinal cord neuropathy loss of myelinated nerve fibers no myelinated retinal fibers		[87,88]
c.4756_4760del (p.N1586Yfs*3)+ putative noncoding mutation, c-het	10	SIRPT2	early childhood	slow progressive gait disturbance & dysarthria limb deformities pes cavus ataxia in limb spastic gait ataxia	hypointense stripes vertical hyperintensities in lateral pons atrophy in superior cerebellar vermis & cervical spinal cord myelinated retinal fibers	Korea (Korean)	[89]
c.8844delT (p.I2949Ffs*4) + c.11781_11782dupGC (p.P3928Rfs*17), c-het	10	SIRPT3 +between XPCB & DNAJ, rs	~20 yrs	early onset cerebellar ataxia gait disturbances weakness in lower extremities	cerebellar & spinal cord atrophy retinal nerve thickening		[90]
c.7272C>A (p.C2424X), c.11319_11321del (p.R3774del), c-het	10	SIRPT3 +XPCB, rs	~10 yrs	gait disturbances dysarthria & dysphagia	cerebellar atrophy retinal striations thickened retinal nerve fiber layer		[91]
c.11803C>T (p.Q3935X)+ 1.33Mb deletion, c-het	10	between SIRPT3 & XPCB	6 yrs	muscle atrophy weakness in distal extremities horizontal gaze nystagmus	cerebellar & spinal cord atrophy thickened retinal nerve fiber layer	China (Chinese)	[92]
c.12637 _12638delGA (p.Q4213Rfs*3)+ c.11274_11276delAAC (p.I3758_ TdelinsM), c-het	10	between XPCB & DNAJ + XPCB, rs	10’s	ataxia limb deformities	sensory–motor neuropathy thickened retinal nerve fibers		[93]
c. 8000T>C (p.F2667S), c. 10685_10689del (p.F3562X), c-het	10	SIRPT3 + between XPCB & DNAJ + XPCB, rs	early childhood	progressive cerebellar symptoms primarily affecting gait dysarthria dysmetria steppage gait pes cavus no spasticity	cerebellar atrophy & thinning of corpus callosum axonal neuropathy mild atrophy in cerebral cortex		[94]
c.5236dupA (p.T1746fs)+ c.13085T/G (p.I4362R), c-het	10	SIRPT2 +DNAJ, rs	NA	typical ARSACS ocular symptoms hearing loss	NA		[96]
c.9019C>T, p.P3007S and c.10174_10183del, p.H3392fs	10	SIRPT2 + between XPCB & DNAJ	early childhood	cerebellar ataxia pyramidal tract signs (lower limbs) dystocia at birth unstable gait incontinence epilepsy limb deformities	sensorimotor neuropathy dysplasia of corpus callosum upper cerebellar vermis atrophy thinning spinal cord swollen papilla		[95]
c.1773C>A (p.S578X) + c.8088_8089 insCA (p.M2697Q fs*43), c-het	8 & 10, rs	SIRPT1 + SIRPT3, rs	6 yrs	cerebellar ataxia reduced muscle strength	peripheral neuropathy cerebellar vermis atrophy hypo-intensities in pons
c.5692 G>T, p.E1898X; c.12673-12677 del TATCA, p.Y4225D fs*6-c-het	10	SIRPT1 +DNAJ, rs	Early childhood	early onset cerebral ataxia slow speech, gait epilepsy limb deformities	Positive Babinski sign mild cerebral & severe cerebellar atrophy thinning spinal cord sensorimotor neuropathy		[97]
c.1773C>A, p.S578X; c.8088-8089 in. CA, p.M2697Q fs*4	10	SIRPT1 + SIRPT3, rs	6 yrs	unstable gait speech disturbances muscle weakness	moderate cerebellar atrophy neuropathy
c.382_383del (p.Q128Sfs*2), hm	7	SIRPT1	2 yrs	nystagmus scanning speech finger dysmetria wide-based gait lower limb spasticity	hypermyelinated nerve fibers spinocerebellar cerebellar atrophy	Thailand (Thai)	[98]
c.5824_5827delTACT (p.Y1942Mfs*9), hm	10	SIRPT2	early teens	cerebellar ataxia limb deformities	demyelination & axonal loss cerebellar atrophy thinning corpus callosum	Kuwait (Kuwait)	[99]
c.429_430delTT (p.W144VfsX39), hm	7	SIRPT1	3 yrs	ataxic gait & dysarthria episodic muscle cramps mirror movements hypokinesia/bradykinesia rigidity	axonal–demyelinating sensorimotor neuropathy	Iran (Iranian)	[100]
c.4117_4118delGCinsAG (p.A1373R), hm	10	SIRPT2	early childhood	progressive muscle weakness poor growth initial diagnosis: SMA-II	NA		[101]
c.14329fs*2725 (p.R707Kfs*6), hm	10	SIRPT2SIRPT1	9–15 yrs	nystagmus pes cavus limb deformities postural tremor & instability no spasticity	sensory motor neuropathy no retinal fiber abnormality	India (Indian)	[102]
c.11690_11693dupGTGA (p.N3898QfsX2),hm	10	XPCB	4 yrs	delay in motor development speech was impaired dysmetria & ataxia in upper limbs loss of balance	cerebellar atrophy, “striped” pontine hypo-intensities myelinated nerve fibers in retina		[103]
c.8605delT (p.C2869VfsX15), hm	10	SIRPT3	14 mths	lowly progressive spastic–ataxic disorder mild intellectual disability	hypointense pontine stripes hyperintense lateral pons thickened retinal nerve fibers		[104]
c.8793 delA, hm	10	SIRPT1	early childhood	delay in motor development slurred speech saccades & broken pursuit movements gaze-evoked nystagmus	striped pons thinning corpus callosum bithalamic stripes		[105]
c. 4232T>G + c.8132C>T, c-het	10	SIRPT2 + SIRPT3, rs	3 yrs	progressive gait ataxia low limb stiffness dysmetria spasticity dysdiachokinesia nystagmus cerebellar gait	cerebellar atrophy striped pons peripheral neuropathy		[106]
c.2656C>T (p.Q886*), hm	10	SIRPT1	11–12 yrs	ataxias spasticity cognitive decline aggressivity seizures rapid progression intellectual disabilities	retinal thickening possible cerebellar atrophy hyperintensities in pons atrophic cerebellar hem spheres	Pakistan (Pakistani)	[107]
c.4756_4760delAATCA (p.N1586Yfs*3), hm	10	SIRPT2	9–10 yrs	ataxia spasticity slight cognitive decline intellectual disabilities	retinal thickening possible linear hypo-intensities in the pons
c.9119dupA (p.N3040Kfs*4), hm	10	SIRPT3	1.5 yrs	spasticity spastic–ataxic gait bradykinesia mild dys tonic postures of upper limbs muscular atrophy	vermal & paravermal cerebellar atrophy thinning of corpus callosum global subcortical atrophy		[108]
p.N2380K & p.D3269N, c-het	10	SIRPT2 + SIRPT3, rs	16 mths	developmental delay nystagmus hearing impairment speech delay brisk deep tendon reflexes decrease in the number of cell mitochondria	retinal degeneration	Israel (Ashkenazi Jews)	[109]