Table: 1.

Summary of the tissue specific symptoms of the repeat expansion diseases with the disease-associated gene

Defected mRNA region	Disease	Defected Gene	Tissue-specific clinical symptoms
			Neuronal Tissues	Other Tissues
5’UTR	FXTAS	FMR1 [158]	Ataxia [159], brain atrophy, white matter lesions [160, 161], cognitive decline, parkinsonism [160], peripheral neuropathy, autonomic dysfunction and short-term memory loss [162].	Premature ovarian failure, hypothyroidism in female [159], limb proximal muscle weakness [160]
	FXS	FMR1 [14]	Autism [163], mental retardation, developmental delay and increased susceptibility to seizures [15].	Macroorchidism [15], cardiac murmur [164], hyperflexible joints, hernias, flat feet [165]
	SCA12	PPP2R2B [166]	Ataxia, cerebral and/or cerebellar atrophy [167], seizures [22].	Dysarthria, action tremors in upper limbs [167].
Intron	DM2	ZNF9 [168]	Cognitive impairment [169], intellectual disability, sleepiness and fatigue [170], brain atrophy, white and grey matter abnormalities [171, 172].	Myotonia, muscle dysfunction, cardiac arrhythmia [40, 173], hypertrophy calf muscles [174].
	ALS	C9orf72 [28, 29]	Motor neuron degeneration, frontotemporal lobar dysfunction, dementia and cognitive impairment [175].	Progressive spasticity, muscle wasting, weakness and muscle atrophy [28]
	FTD	C9orf72 [28, 29]	Frontotemporal lobar dysfunction, motor neuron dysfunction [176], changes in personality, behavior, and language ability, dementia [175].	Fasciculation, muscle atrophy, weakness [177].
Coding Region	Polyglutamine (PolyQ) diseases
	SBMA	AR [21]	Lower motor neuron degeneration [178], androgen insensitivity [22].	Muscle weakness, gynecomastia and reduced fertility [22, 178]
	HD	HTT [179]	Cognitive decline and dementia [22], dystonia [180].	Chorea [22], movement disorder [181].
	DRPLA	ATN1 [182–184]	White matter lesion, neural loss, ataxia, seizures, choreoathetosis, dementia [22, 185], myoclonus, epilepsy [184].	Chorea, incoordination [185]
	SCA 1,2,3,6,7,17	Ataxin 1 [186, 187], Ataxin 2 [188–190], Ataxin 3 [191], CACNA1A [192], Ataxin 7 [193], TBP [194]	Ataxia, tremor, and dysarthria, parkinsonism (SCA3), retinal dystrophy (SCA7), seizures (SCA17) [22].	Slurred speech (SCA1); Hyporeflexia (SCA2) Cardiac dysfunction (SCA7) [22].
	Poly Alanine (Poly A) diseases
	OPMD (OPMD)	PABPN1 [195]	-(no data)	Eyelid ptosis and dysphagia [195], involuntary muscle weakness [196].
	XLMR	ARX [197]	Cognitive impairment [198], mental retardation [199], dysarthria [200].	Involuntary hand movements (MRXS), growth abnormality [200].
3’UTR	DM1	DMPK [37]	Neuropsychiatric disturbances, cognitive defeats, sleepiness and fatigue; brain atrophy [169], white and grey matter abnormalities [201], mood disorder, emotion problem and memory problem.	Myotonia, muscle wasting, cardiac arrhythmias, insulin resistance, gastrointestinal dysfunctions, posterior iridescent cataracts [54]
	SCA8	ATXN8 [202]	Cerebellar atrophy[203], progressive ataxia[204].	Limb ataxia, dysarthria, nystagmus, spasticity [22].

Abbreviations: Fragile X associated tremor/ataxia syndrome (FXTAS); Fragile X Syndrome (FXS); Spinocerebellar ataxia type 12 (SCA12); Myotonic Dystrophy type 2 (DM2); Amyotrophic lateral sclerosis (ALS); Frontotemporal degeneration (FTD); Spinal and Bulbar Muscular Atrophy (SBMA); Huntington disease (HD); Dentatorubral pallidoluysian Atrophy (DRPLA); Spinocerebellar Ataxias (SCA); Polyalanine (PolyA) diseases; Oculopharyngeal muscular dystrophy (OPMD); Syndromic and non-syndromic X-linked mental retardation (XLMR); Myotonic Dystrophy type 1 (DM1)