Comprehensive phenotype of the p.Arg420his allelic form of spinocerebellar ataxia type 13

Abstract

The p.Arg420His allelic form of spinocerebellar ataxia type 13 has been reported in a large Filipino kindred, as well as three European index cases, one with an affected offspring. Haplotype analysis has confirmed independent mutational events. All individuals share adult-onset, predominantly cerebellar signs and a slowly progressive course. However, a comprehensive phenotypic description has yet to be published on SCA13(p.Arg420His). In this study, we present the results of a detailed neurological clinical and diagnostic testing on 21 mutation-positive members of a four-generation Filipino family to further define this disease, aiding diagnosis and prognosis.

Fig. 1

Pedigree showing an extended SCA13 Filipino family. Filled black symbols are clinically affected individuals with known c.1259G>A genotype. Gray symbols represent asymptomatic examined individuals with known genotype. White insets indicate two wild-type alleles. Of the remaining 12 at-risk individuals, nine are c.1259G>A heterozygotes and three are wild type. They are not identified for privacy concerns. Bold numbers indicate the ages at examination and disease onset

Fig. 2

MR T1 midline sagittal and T2 axial sequences (inset) suggest progressive cerebellar atrophy with disease duration (dd) and SARA severity (ss) (a disease duration 5 years, SARA 8.5; d disease duration 25 years, SARA 11). Panels b and e (daughter) and c and f (mother) are repeated studies with a 5-year interval between initial and subsequent examination and imaging (a, b 33/38 years; c, d 68/73 years). There is little change in the degree of cerebellar vermian atrophy over 5 years though progression of disease was evident in an increased SARA from 2 to 10.5 (b, e) and from 27 to 32.5 (c, f). The brain stem and pons remain intact in spite of a 48-year disease duration (f)