Balkan Journal of Medical Genetics

THE UTILITY OF WHOLE EXOME SEQUENCING IN DIAGNOSING PEDIATRIC NEUROLOGICAL DISORDERS
Muthaffar OY
*Corresponding Author: Osama Y. Muthaffar, M.D., Department of Pediatrics, King Abdulaziz University, Jeddah, PO Box 80215, Jeddah 21589, Kingdom of Saudi Arabia. Tel.: +96-12-640-1000 (ext. 20208). Fax: 996-12-640-3975. E-mail: oymuthaffar@kau.edu.sa; osamam@hotmail.com
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DISCUSSION

The introduction of WES in medicine has changed the way of physician’s approach to patients. The number of newly diagnosed neurogenetic conditions and mutations are increasing. Multiple studies worldwide reviewed WES findings, however, few in the Middle East region. In Saudi Arabia, the Arabic ethnic background is the main population structure. Consanguinity is common in marriages. Thus, more metabolic and neurogenetic conditions are prevalent in our region. In this study, 19 patients (73.0%) out of 26 patients had genetically and phenotypically consistent findings. In the WES-positive group, consanguinity was present in 53.0% of the families whereas in the WES-negative it was 15.0%. Compared to other studies in the region [18,19] 43.0-49.0% of WES results showed clinically significant results in Saudi Arabia. Other studies from the United Arab Emirates and Qatar, reached 54.0-68.0% genetically confirmed diagnoses [14,15]. Larger studies including 2000-3000 WES samples from different ethnic regions, showed a lower diagnostic rate, around 25.0% from the USA [11], Care4Rare Canada [20] and Finding of Rare Disease Genes (FORGE) [21]. Consanguinity was positive in 18 families of the cohort (69.0%). In other studies, a similar rate of 66.0-75.0% of consanguinity was reported [12,14]. The most common features of WES results in the Middle East are a high percentage of consanguinity and a higher positivity rate of WES results [22,23]. Whole exome sequencing has a direct impact on management [24]. For example, patient number #5 (Table 3) had a positive BTD mutation classified as pathogenic. He was 7 years old when diagnosed with biotinidase deficiency. His symptoms were noticed by his parents since he was 3 years old. He had hearing problems, ataxia, convulsions and intermittent encephalopathy. He was in coma and ventilatory-dependent when WES was requested. Once started on biotin supplements, he gradually started to improve. Currently, he is off the ventilator. He is redeveloping motor gains with physical therapy. He has not experienced any more convulsions and his hearing has improved. Another patient in the cohort has a pathogenic RANBP2 gene mutation. He presented with acute necrotizing encephalopathy (ANE) (Figure 2). A few months after being diagnosed, his sister was also diagnosed with clinical ANE. Unfortunately, both siblings died despite aggressive immunotherapy. In conclusion, WES is an integral diagnostic tool in a pediatric neurology clinic. It is of great importance to unravel the diagnostic odyssey of many neurological and neurogenetic conditions. Family counseling, prevention of recurrence and treatment depends on proper genetic diagnoses. Pricing of WES is still a challenge at many centers and countries [25,26]. Sometimes, WES results can also take more than 2-3 months that can delay WES-focused medical care. The high yield of WES results in this study, though a small number of patients, is compatible with similar studies. This study promotes performing WES in childhood neurological disorders, especially when these is a similar family history and positive consanguinity. Declaration of Interest. The authors report no conflicts of interest. The authors alone are responsible for the content and writing of this article.

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