TITLE:
Whole Exome Sequencing: Novel Genetic Polymorphisms in Saudi Arabian Attention Deficit Hyperactivity Disorder (ADHD) Children
AUTHORS:
Neda Mostafa Bogari, Amr Ahmed Amin, Ashwag Aljohani, Ghida Dairi, Mahmoud Zaki El-Readi, Anas Dannoun, Udaya Raja, Mohammad Adil, Nermeen Qutub, Suhair Alhelfawi, Amal Alobaidi, Derar Alqudah, Hussain Banni, Safaa Yehia Eid, Huda Balto, Faisal Al-Allaf, Mohiuddin Taher, Hiba Saed Al-Amoodi, Ahmed Fawzy
KEYWORDS:
Next Generation DNA Sequencing, Single Nucleotide Polymorphisms, Saudi Children, Attention-Deficit Hyperactivity Disorder, ADHD
JOURNAL NAME:
Natural Science,
Vol.11 No.2,
February
28,
2019
ABSTRACT: Background:
Attention-deficit hyperactivity disorder (ADHD) is a widespread and
debilitating disorder with relatively high prevalence in Saudi Arabia.
Neuropsychological and radiological investigations have revealed that there are
some differences in the components of the brain regions in children with and
without ADHD. In this study we have performed whole exome sequencing (WES) in
four non-familial cases of ADHD from Makkah Region to identify the genetic
polymorphisms associated with the disease in our Saudi population. Methods: Exome
sequencing was carried out using Ion Proton with AmpliSeq Exome library
methods, and the data were analysed by Ion Reporter 5.6 software. Results: A
total of 33 variants were identified from 222 genes selected from the GWAS
catalogue for ADHD associated genes. However, the SNPs we identified in these
genes were not reported to be associated with ADHD in previous studies. We have
identified 2 novel missense variants; one in c.3451G > T; p. (Ala1151Ser) in
ITGA1 gene and another is c.988G > A; p. (Ala330Thr) in SPATA13 genes. The
variants rs928661, rs11150370 and rs386792899 were the only three variants that
appeared on all the 4 patients studied. Six missense variants, rs16841277,
rs2228209, rs2230283, rs3741883, rs1716 and rs2272606, were found in 3
different patients, respectively. However, the three documented variants are
rs13166360 with bipolar disorder, rs920829 with neuropathic pain, and rs6558702
with schizophrenia. Conclusion: We have identified 2 novel variants in ADHD
children. SIFT score of all variants indicates that these substitutions have
damaging effects on the protein function. Further screening studies are
recommended for confirmation.