Genetic and phenotypic features of patients with childhood ataxias diagnosed by next-generation sequencing gene panel

The purpose of this prospective study was to identify the characteristics of pediatric recessive ataxias and the mutations leading to them.

Eighty-four pediatric patients aged 0-18 years presenting to our clinic, evaluated by means of imaging, metabolic or pathological investigation, or single-gene test, in whom Friedreich's ataxia was excluded, and predicted to carry the progressive autosomal recessive ataxia gene were included in the study. Patients' demographic, clinical, laboratory, and radiological characteristics were recorded. DNA and panel sequencing directed toward ataxia-related genes was performed using the next-generation sequencing method.

A molecular diagnosis was established in 21 (25%) of the 84 patients. Genetically, infantile neuroaxonal dystrophy (7/21), ataxia with oculomotor apraxia type 1 (5/21), neuronal ceroid lipofuscinosis type 5 (2/21), ataxia with oculomotor apraxia type 2 (1/21), Lafora disease (1/21), tremor ataxia syndrome accompanying central hypomyelination (1/21), Charlevoix-Saguenay ataxia (1/21), Marinesco-Sjögren syndrome (1/21), VLDRL-associated cerebellar hypoplasia (1/21), and TSEN54-related pontocerebellar hypoplasia (1/21) mutations were detected.

Approximately 25% of our patients were diagnosed. Novel mutations in the known genes were identified and are important in terms of phenotype-genotype correlation.