Abstract
INTRODUCTION: TPP1 variants have been identified as a causative agent of neuronal ceroid lipofuscinosis 2 disease, that ataxia is one of its clinical features. Therefore, here, molecular study of TPP1 variants is presented in an Iranian cohort and a novel pathogenic variant is described. METHODS: This investigation was conducted as a cross-sectional study in a tertiary referral hospital, Children's Medical Center, Pediatrics Center of Excellence. Clinical presentations and pedigrees were documented. Patients with cerebellar ataxia were enrolled in this study. Next-generation sequencing was applied to confirm the diagnosis. Segregation and bioinformatics analyses were also done for the variants using Sanger sequencing. RESULTS: Forty-five patients were included in our study. The mean age of onset was 104 (+55.60) months (minimum = 31 months, maximum = 216 months). The majority of cases (73.3%) were born to consanguineous parents and only 1 patient (2.2%) had an affected sibling. Of the 45 patients, only 1 patient with a novel pathogenic variant (c.1425_1425+1delinsAT, p.A476Cfs*15) in the TPP1 gene was identified. DISCUSSION: The main strength of current study is the relatively large sample size. Besides, a novel pathogenic variant could be important toward the diagnosis and management of this condition. With significant advances in various therapies, early diagnosis could improve the treatments using personalized-based medicine.