title: Utilization of amplicon-based targeted sequencing panel for the massively parallel sequencing of sporadic hearing impairment patients from Saudi Arabia.
abstract: BACKGROUND
  Hearing Impairment (HI) can have genetic or environmental causes and in some cases, an interplay of both. Genetic causes are difficult to determine as mutations in more than 90 genes have been shown recently to be responsible for HI. Providing a genetic diagnostic test for HI is therefore a challenge especially for ethnic groups where GJB2 mutations are shown to be rare.
  
  
  RESULTS
  Here we show the design and implementation of an amplicon-based targeted sequencing panel that allows the simultaneous sequencing of 87 HI genes. Mutations identified included known pathogenic mutations and novel variants with unknown significance. The diagnostic rate of this panel is 28 % when only pathogenic variants were reported. However, an additional 28 % harbored recurrent combinations of novel or rare single nucleotide variants in the OTOF or PCDH15 genes. Such combinations were not identified in healthy individuals.
  
  
  CONCLUSIONS
  Targeted sequencing approach is a very useful strategy for the identification of mutations affecting the HI genes because of its relatively fast turn-around time and cost effectiveness compared to whole-exome sequencing. Further novel or rare variants could be identified by implementing a large-scale screening of HI using our panel which will eventual lead to a higher diagnostic rate.
authors: Center of Innovations in Personalized Medicine, King Abdulaziz University, P.O. Box 80216, Jeddah, 21589, Kingdom of Saudi Arabia. adallol@kau.edu.sa.|Center of Excellence in Genomic Medicine Research, King Abdulaziz University, Jeddah, Kingdom of Saudi Arabia. adallol@kau.edu.sa.
authors: Ashraf
authors: A
authors: Dallol
authors: Center of Excellence in Genomic Medicine Research, King Abdulaziz University, Jeddah, Kingdom of Saudi Arabia.
authors: Kamal
authors: K
authors: Daghistani
authors: Center of Innovations in Personalized Medicine, King Abdulaziz University, P.O. Box 80216, Jeddah, 21589, Kingdom of Saudi Arabia.
authors: Aisha
authors: A
authors: Elaimi
authors: Center of Innovations in Personalized Medicine, King Abdulaziz University, P.O. Box 80216, Jeddah, 21589, Kingdom of Saudi Arabia.
authors: Wissam A
authors: WA
authors: Al-Wazani
authors: King Abdulaziz University Hospital, King Abdulaziz University, Jeddah, Kingdom of Saudi Arabia.
authors: Afaf
authors: A
authors: Bamanie
authors: Jeddah Institute for Speech and Hearing, Jeddah, Kingdom of Saudi Arabia.
authors: Malek
authors: M
authors: Safiah
authors: King Fahad General Hospital, Jeddah, Kingdom of Saudi Arabia.
authors: Samira
authors: S
authors: Sagaty
authors: Faculty of Applied Medical Sciences, King Abdulaziz University, Jeddah, Kingdom of Saudi Arabia.
authors: Layla
authors: L
authors: Taha
authors: Center of Innovations in Personalized Medicine, King Abdulaziz University, P.O. Box 80216, Jeddah, 21589, Kingdom of Saudi Arabia.
authors: Rawabi
authors: R
authors: Zahed
authors: Center of Innovations in Personalized Medicine, King Abdulaziz University, P.O. Box 80216, Jeddah, 21589, Kingdom of Saudi Arabia.|King Abdulaziz University Hospital, King Abdulaziz University, Jeddah, Kingdom of Saudi Arabia.
authors: Osama
authors: O
authors: Bajouh
authors: Center of Excellence in Genomic Medicine Research, King Abdulaziz University, Jeddah, Kingdom of Saudi Arabia.
authors: Adeel Gulzar
authors: AG
authors: Chaudhary
authors: Center of Excellence in Genomic Medicine Research, King Abdulaziz University, Jeddah, Kingdom of Saudi Arabia.
authors: Mamdooh Abdullah
authors: MA
authors: Gari
authors: King Abdulaziz University Hospital, King Abdulaziz University, Jeddah, Kingdom of Saudi Arabia.
authors: Rola
authors: R
authors: Turki
authors: Center of Excellence in Genomic Medicine Research, King Abdulaziz University, Jeddah, Kingdom of Saudi Arabia.
authors: Mohammed Hussein
authors: MH
authors: Al-Qahtani
authors: Center of Innovations in Personalized Medicine, King Abdulaziz University, P.O. Box 80216, Jeddah, 21589, Kingdom of Saudi Arabia.|Center of Excellence in Genomic Medicine Research, King Abdulaziz University, Jeddah, Kingdom of Saudi Arabia.|Faculty of Applied Medical Sciences, King Abdulaziz University, Jeddah, Kingdom of Saudi Arabia.
authors: Adel Mohammed
authors: AM
authors: Abuzenadah
mesh_terms: D000293:Adolescent; D000328:Adult; D000070585:Cadherin Related Proteins; D015820:Cadherins / Q000235:genetics; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D004247:DNA / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism; D030541:Databases, Genetic; D005260:Female; D005838:Genotype; D034381:Hearing Loss / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D059014:High-Throughput Nucleotide Sequencing / Q000379:methods* / Q000592:standards; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D015203:Reproducibility of Results; D012529:Saudi Arabia; D055815:Young Adult
chemical_list: C498835:CDHR15, human; D000070585:Cadherin Related Proteins; D015820:Cadherins; D008565:Membrane Proteins; C118457:OTOF protein, human; D004247:DNA
keywords: Hearing impairment; NGS; Saudi Arabia; Targeted sequencing