Exome sequencing in diagnosis of rare neurogenetic disorders

Paria Najarzadeh torbati,1 Najmeh ahangari,2 Mehranbeiraghi toosi,3 Mohammad doosti,4 Ehsan ghayoor karimiani,5,*

1. Next Generation Genetic Polyclinic, Mashhad, Iran
2. Next Generation Genetic Polyclinic, Mashhad, Iran
3. Pediatric Neurology Department, Ghaem hospital, Mashhad University of Medical Sciences, Mashhad, Iran
4. Next Generation Genetic Polyclinic, Mashhad, Iran
5. Honorary Research Associate, University of Manchester, UK



Diagnostic courses for neurogenetic disorders often require the use of substantial time and resources.previous studies have shown exome sequencing increased diagnostic and clinical utility in medical genetics. although genetic heterogeneity in neurogenetic disorders has been an obstacle to phenotype-based diagnostic testing, exome sequencing improved the presumptive diagnostic rate in patients from 25% to 48%. our objective was to describe the role of exome sequencing in a group of patients with neurogenetic disorders.


Five families with at least two affected individuals and mendelian inheritance pattern compatible with genetic disorders such as intellectual disability, seizures, epilepsy, paralysis, speech difficulties, vision and hearing problem have been conducted. a complete clinical and paraclinical examination has been done by expertspecialists and clinical geneticist. genomic dna was extracted and evaluated through whole exome sequencing followed by bioinformatic analysis. parents and healthy offspring were assessed for the candidate gene variants.


We have found genetic variations in genes such as mfsd8, cln6, atm, clp1, atrx which have been reported previously or were novel variants based on computational prediction using bioinformatic tools. at the present time, powerful sequencing techniques are identifying large numbers of genetic variants associated with unique phenotypes.


We have demonstrated that exome sequencing as a high throughput molecular technique has rapidly become a component of the clinical approach that require a broad search for causal variants across the spectrum of genetically heterogeneous mendelian disorders.


Exome sequencing, genetics, neurogenetic disorders, diagnosis