Table 2.

Hereditary Ataxias Caused by Nucleotide Repeat Expansions: Molecular Genetics


Gene 1		% of Pathogenic VariantsNucleotide Repeat (Amino Acid)Repeat LocationNormal Repeat NumberFull-Penetrance Pathogenic Repeat NumberComment
ATN1 100CAG (Gln)Exon 56-35≥48
ATXN1 100CAG (Gln)Exon 86-35≥39
ATXN2 100CAG (Gln)Exon 1≤31≥33
ATXN3 100CAG (Gln)Exon 812-4460-87
ATXN7 100CAG (Gln)Exon 14-19≥36
ATXN8 100CAG (Gln)Exon 1~80Unknown
ATXN8OS 100CTG3' UTR15-50 CTA/CTG≥71-1300 CTA/CTG 2Penetrance is <100%. 2
ATXN10 100ATTCTIntron 910-32≥800Repeat interruptions are assoc w/presence of seizures.
BEAN1 100TGGAAIntron 602.5- to 3.8-kb insertion
CACNA1A 3>99CAG (Gln)Exon 7≤1820-33See Table 3 for phenotype assoc w/variants that are not nucleotide repeat disorders.
FGF14 100GAA (Glu)Intron 1<250>300
FMR1 >99CGG5' UTR5-44≥200Premutation alleles: 55-200 CGG repeats
FXN ~98GAAIntron 15-33≥66In about 5% of affected persons 1 FXN allele is an expanded GAA repeat & 1 is a pathogenic missense variant.
NOP56 100GGCCTGIntron 13-14≥650
PPP2R2B 100CAGPromoter7-3151-78
RFC1 100AAGGG 4Intron 2Unknown~400-~2000ACAGG repeat expansion has been reported in 3 persons from Asian & Asian Pacific populations. 4
TBP 100CAG or CAA (Gln)Exon 325-40≥49
1.

Genes are listed in alphabetic order.

2.

While penetrance less than 100% has been reported at all repeat sizes, higher penetrance is reported for CTA/CTG repeat sizes of 80-250 [Ranum et al 1999].

3.

The majority of CACNA1A pathogenic variants are CAG repeat expansions associated with spinocerebellar ataxia type 6. Heterozygous CACNA1A missense, nonsense, splice site, frameshift, and exon/multiexon deletions have been reported in individuals with episodic ataxia type 2 and progressive cerebellar ataxia.

4.

RFC1 intron 2 contains a microsatellite region with variable benign AAAAG repeats (range: 11-200 repeats) and/or benign AAAGG repeats (range: 40-1000 repeats). Interruption of the benign AAAAG/AAAGG repeated units with biallelic pathogenic AAGGG expansions has been identified in individuals with RFC1 CANVAS / spectrum disorder [Cortese et al 2019].

From: Hereditary Ataxia Overview

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