Molecular and clinical correlation in five Indian families with spinocerebellar ataxia 12

Abstract

Spinocerebellar ataxia 12 (SCA12) is a recently identified form of autosomal dominant cerebellar ataxia associated with the expansion of an unstable CAG repeat in the 5' untranslated region of the gene PPP2R2B. We analyzed 77 Indian families with autosomal dominant cerebellar ataxia phenotype and confirmed the diagnosis of SCA12 in 5 families, which included a total of 6 patients and 21 family members. The sizes of the expanded alleles ranged from 55 to 69 CAG repeats, and the sizes of the normal alleles ranged from 7 to 31 repeats. We believe our study is the first to demonstrate that SCA12 may not be as rare in some populations as previously thought.

Evidence of a Common Founder for SCA12 in the Indian Population

“…The repeat length ranged from 8-23 triplets in normal individuals. Anticipation, which was not detected in previous analyses (Fujigasaki et al 2001;O'Hearn et al 2001;Srivastava et al 2001;Holmes et al 2003), was also not observed in this larger study. The age at onset of the disease ranged from 26 to 56 years (mean 40.2 years) and the duration of illness at the time of examination varied from 1 to 22 years.…”

“…The 20 Indian families also included 5 families we reported in an earlier study (Srivastava et al 2001). As two unrelated affected individuals were present in one of the families (AT164), the Indian dataset included 21 unrelated expanded chromosomes.…”

“…This has been attributed to the ethnicity, diversity and inherent genetic differences between sub-populations. SCA12, first reported in a large American pedigree of German descent (Holmes et al 1999;O'Hearn et al 2001) has been subsequently reported only in Indian families (Fujigasaki et al 2001;Srivastava et al 2001). In an earlier study, expansion in the PPP2R2B gene was reported in 6 patient, and 3 asymptomatic at-risk individual, in 5 Indian families (Srivastava et al 2001), which suggested that SCA12 is not rare in India.…”

“…Gait abnormalities are typically mild or absent. Other signs may include slow saccades, broken pursuits, horizontal nystagmus, facial myokymia and axial dystonia Srivastava et al 2001).…”

Frequencies of spinocerebellar ataxia subtypes in Thailand: window to the population history?

“…On the contrary, apart from the studies carried out in West Bengal, which reported the relative frequency of SCA3/MJD of approximately 36%, 24 the reported relative frequency of SCA3/MJD ranged from 0 to about 14% in most studies in Indian populations. 19,20,21,23 The West Bengal study is in fact an interesting exception, as earlier studies have shown a genetic relationship between the population in this area and the Tibeto-Burman speakers from Southeast and East Asia. [26][27][28][29] Also, interestingly, in Singaporeans who a are mixture of ethnic Chinese, Malays and Indians, the relative frequency of SCA3/MJD was even lower than that in ours, at about 13%.…”