Mutations in ATXN2 cause spinocerebellar ataxia type 2 (SCA2). The autosomal dominant cerebellar ataxias (ADCA) are a heterogeneous group of neurodegenerative disorders characterized by progressive degeneration of the cerebellum, brain stem and spinal cord. Clinically, ADCA has been divided into three groups: ADCA types I-III. ADCAI is genetically heterogeneous, with five genetic loci, designated spinocerebellar ataxia (SCA) 1, 2, 3, 4 and 6, being assigned to five different chromosomes. ADCAII, which always presents with retinal degeneration (SCA7), and ADCAIII often referred to as the `pure' cerebellar syndrome (SCA5), are most likely homogeneous disorders. Several SCA genes have been cloned and shown to contain CAG repeats in their coding regions. SCA2 is caused by the expansion of a CAG repeat in the coding region of the ATXN2 gene producing an elongated polyglutamine tract in the corresponding protein. The expanded repeats are variable in size and unstable, usually increasing in size when transmitted to successive generations. The function of the ataxins is not known. This locus has been mapped to chromosome 12, and it has been determined that the disease allele usually contains 34-52 CAG repeats, but can contain as few as 32 or more than 100. Normal alleles usually have 22 or 23 repeats, but can contain up to 31 repeats. A potential transcript variant, missing an internal coding exon, has been described; however, its full-length nature is not certain.
^Gispert S, Twells R, Orozco G, Brice A, Weber J, Heredero L, Scheufler K, Riley B, Allotey R, Nothers C; et al. (Sep 1993). "Chromosomal assignment of the second locus for autosomal dominant cerebellar ataxia (SCA2) to chromosome 12q23-24.1". Nat Genet4 (3): 295–9. doi:10.1038/ng0793-295. PMID8358438.
^Margolis RL, Abraham MR, Gatchell SB, Li SH, Kidwai AS, Breschel TS, Stine OC, Callahan C, McInnis MG, Ross CA (Jul 1997). "cDNAs with long CAG trinucleotide repeats from human brain". Hum Genet100 (1): 114–22. doi:10.1007/s004390050476. PMID9225980.
Stevanin G, Dürr A, Brice A (2000). "Clinical and molecular advances in autosomal dominant cerebellar ataxias: from genotype to phenotype and physiopathology.". Eur. J. Hum. Genet.8 (1): 4–18. doi:10.1038/sj.ejhg.5200403. PMID10713882.
Pulst SM, Nechiporuk A, Nechiporuk T; et al. (1996). "Moderate expansion of a normally biallelic trinucleotide repeat in spinocerebellar ataxia type 2.". Nat. Genet.14 (3): 269–76. doi:10.1038/ng1196-269. PMID8896555.
Sanpei K, Takano H, Igarashi S; et al. (1996). "Identification of the spinocerebellar ataxia type 2 gene using a direct identification of repeat expansion and cloning technique, DIRECT.". Nat. Genet.14 (3): 277–84. doi:10.1038/ng1196-277. PMID8896556.
Imbert G, Saudou F, Yvert G; et al. (1996). "Cloning of the gene for spinocerebellar ataxia 2 reveals a locus with high sensitivity to expanded CAG/glutamine repeats.". Nat. Genet.14 (3): 285–91. doi:10.1038/ng1196-285. PMID8896557.
Sahba S, Nechiporuk A, Figueroa KP; et al. (1998). "Genomic structure of the human gene for spinocerebellar ataxia type 2 (SCA2) on chromosome 12q24.1.". Genomics47 (3): 359–64. doi:10.1006/geno.1997.5131. PMID9480749.
Huynh DP, Figueroa K, Hoang N, Pulst SM (2000). "Nuclear localization or inclusion body formation of ataxin-2 are not necessary for SCA2 pathogenesis in mouse or human.". Nat. Genet.26 (1): 44–50. doi:10.1038/79162. PMID10973246.
Choudhry S, Mukerji M, Srivastava AK; et al. (2002). "CAG repeat instability at SCA2 locus: anchoring CAA interruptions and linked single nucleotide polymorphisms.". Hum. Mol. Genet.10 (21): 2437–46. doi:10.1093/hmg/10.21.2437. PMID11689490.
Pang JT, Giunti P, Chamberlain S; et al. (2002). "Neuronal intranuclear inclusions in SCA2: a genetic, morphological and immunohistochemical study of two cases.". Brain125 (Pt 3): 656–63. doi:10.1093/brain/awf060. PMID11872620.