Background and Aims:

Since last few years genetic testing has become easily available. In developing countries where cost may forbid testing, evaluating clinical exome sequencing(CES) might be financially more feasible than whole exome sequencing (WES) for heterogenous mendelian disorders. However there are few studies to assess diagnostic yield of CES.

Our study looked at diagnostic yield of clinical exome panel for phenotypic subgroup of neurological disorder with a presumed genetic aetiology.

Methods:

Retrospective analysis of all patients who were subjected to CES between 2016 and 2019 at neurology department of KEM hospital was done. It was done in patients in whom clinical picture was highly suggestive of genetic aetiology. CES data was generated at standard genetic laboratory

Results:

Exome data from 95 adult and child neurological patients were analysed. Likely or definite causative variants were found in 52 individuals, achieving an overall diagnostic rate of 55%. Molecular diagnosis could be established in 34/47 (72%) patients with neuromuscular disease, 6/24 (25%) with epileptic disorders, 6/14 (43%) with movement disorders and 6/10 (60%) with suspected intellectul disability and delay. In 20(21%) patients the management changed in terms of specific drugs and diet.

Conclusions:

Diagnostic CES identified underlying genetic defect definitively or likely in 55% of neurological patients. Highest diagnostic yield was achieved in neuromuscular group (72%). Diagnostic yield was high because of stringent selection of patients. Confirmation of diagnosis by genetics paves way for genetic counselling, avoids invasive diagnostic tests and decreases economic burden to family.