Familial Spinal Cerebellar Ataxia11 In China

Background:Spinal cerebellar ataxia 11(SCA11)is a rare disease,characterized by progressive cerebellar ataxia,abnormal eye sign.The diagnosis of SCA11 was determined by molecular genetic detection of heterozygous pathogenic variants in TTBK2.Five families have been reported in the past.We report the first family with spinocerebellar ataxia 11 in China.Methods:A careful investigation of the clinical manifestations,brain imaging,electrophysiological and exome and Sanger sequencing were utilized to identify pathogenic genetic variants in a three-generation pedigree that includes 5 affected individuals.The clinical manifestations,brain imaging,electrophysiological and genetic characteristics of the family were analyzed retrospectively.ResultsThe proband and affected members began to develop cerebellar ataxia,dysarthria,nystagmus,and strabismus at approximately age 40 for no apparent reason.Brain MRIs showed cerebellar atrophy and slight atrophy of the bulbar medulla.Electromyography showed extensive neurogenic damage.Sensory evoked potentials of lower limbs showed damage to the spinal-brainstem-cortical conduction pathway.Genetic analysis revealed a novel point mutation(c.3290T>C)in the TTBK2 gene encoding tau-microtubule kinase 2,which led to an amino acid exchange(p.Val1097Ala).The missense mutation segregated with the phenotype.The mutation has a very low mutation rate in the population,the variant amino acids are highly conserved among species,and protein function damage prediction at the mutation site is detrimental and is highly likely to cause protein damage.The pathogenicity prediction of the mutation site shows that it is likely to cause disease.This variation is consistent with the diagnosis of SCA11.Conclusions:The first SCA11-affected family in China had gait instability,dyspraxia and dysarthria,significant cerebellar atrophy,slight atrophy of the medulla oblongata,and some affected individuals with peripheral nerve damage.The pathogenic allele was a c.3290T>C mutation in the TTBK2 gene.