Compound heterozygous mutations in the TPP1 gene causes the rare Autosomal recessive spinocerebellar ataxia type 7 : A case report and review

Abstract Background: Spinocerebellar ataxia type (SCA) type 7 is an inherited neurological disorder that can be inherited as autosomal dominant, autosomal recessive, X-linked, or mitochondrial. In clinical practice, the most common type of SCA7 is autosomal dominant, and the autosomal recessive spinocerebellar ataxia 7 (SCAR7) has been rarely reported. Here, we report the first case of SCAR7 from China with compound heterozygous missense mutations in the Tripeptidyl peptidase-I (TPP1) gene. Case presentation: A 25-year-old female patient presented with difficulty in walking, easy falling, accompanied by limb shaking, unstable holding objects, slurred speech, choking and coughing when drinking water, palpitations, easy hunger, and hyper-eating without obvious causes 12 years ago. She was admitted to a tertiary general hospital for a cranial MRI examination, which showed cerebellar atrophy. The patient had dysarthria, and had horizontal nystagmus in both eyes for left vision. She was not stable and precise enough in the bilateral finger-nose test and heel and knee shin test and showed Romberg's sign (+). Wechsler Adult intelligence test suggested mild intelligence defect. Genetic testing showed that there were two compound heterozygous mutations in the TPP1 gene. The patient was diagnosed as SCAR7. Conclusions: The results of autosome testing and sequencing showed that the SCAR7 case was caused by compound heterozygous mutations of the TPP1 gene (c.1468G>A p.Glu490Lys and c.1417G>A p.Gly473Ary). This mutation has not been reported in the Chinese population and is a rare novel mutation. This finding provides a new starting point for the study of the SCAR7 gene.