Novel compound heterozygous mutations in WDR62 gene leading to developmental delay and Primary Microcephaly in Saudi Family

A novel compound heterozygous mutation in WDR62gen

  • Muhammad Imran Naseer King Abdulaziz University
  • Mahmood Rasool Center of Excellence in Genomic Medicine Research, King Abdulaziz University, 21589, Jeddah, Kingdom of Saudi Arabia.
  • Angham Abdulrahman Abdulkareem Center of Excellence in Genomic Medicine Research, King Abdulaziz University, 21589, Jeddah, Kingdom of Saudi Arabia.
  • Adeel G. Chaudhary Center of Excellence in Genomic Medicine Research, King Abdulaziz University, 21589, Jeddah, Kingdom of Saudi Arabia.
  • Syed Kashif Zaidi Center of Excellence in Genomic Medicine Research, King Abdulaziz University, 21589, Jeddah, Kingdom of Saudi Arabia.
  • Mohammad H. Al-Qahtani Center of Excellence in Genomic Medicine Research, King Abdulaziz University, 21589, Jeddah, Kingdom of Saudi Arabia.
Keywords: Compound heterozygous mutation, Primary Microcephaly, Saudi Family, WDR62

Abstract

Objective: Primary microcephaly (MCPH) is a rare autosomal recessive disorder characterized by impaired congenital reduction of brain size along with head circumference and intellectual disability. MCPH is a heterogeneous disorder and more than twenty four genes associated with this disease have been identified so far. The objective of this study was to find out the novel genes or mutations leading to the genetic defect in a Saudi family with primary microcephaly.

Methods: Whole exome sequencing was carried out to find the novel mutation and the results was further validated using Sanger sequencing analysis. This study was done in the Center of excellence in Genomic Medicine and Research, King Abdulaziz University under KACST project during 2017 and 2018.

Results: We report a novel compound heterozygous mutations c.797C>T in exon 7 and c.1102G>A in exon 9 of the WD repeat domain 62 (WDR62) (OMIM 604317) gene in two affected siblings in Saudi family with intellectual disability, speech impediments walking difficulty along with primary microcephaly. Two rare, missense variants were detected in heterozygous state in the WDR62 gene in these two affected individuals from the heterozygous parents.

Conclusions: A compound heterozygous mutations c.797C>T in exon 7 and c.1102G> A in exon 9 of the WDR62 gene was identified. WDR62 gene is very important gene and mutation can lead to neuro developmental defects, brain malformations, reduced brain and head size. These results should be taken into consideration during prognostic discussions and mutation spectrum with affected patients and their families in the Saudi population.

doi: https://doi.org/10.12669/pjms.35.3.36

How to cite this:
Naseer MI, Rasool M, Abdulkareem AA, Chaudhary AG, Zaidi SK, Al-Qahtani MH. Novel compound heterozygous mutations in WDR62 gene leading to developmental delay and Primary Microcephaly in Saudi Family. Pak J Med Sci. 2019;35(3):764-770.  doi: https://doi.org/10.12669/pjms.35.3.36

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Author Biographies

Mahmood Rasool, Center of Excellence in Genomic Medicine Research, King Abdulaziz University, 21589, Jeddah, Kingdom of Saudi Arabia.

Associate Professor

Adeel G. Chaudhary, Center of Excellence in Genomic Medicine Research, King Abdulaziz University, 21589, Jeddah, Kingdom of Saudi Arabia.

Professor

Syed Kashif Zaidi, Center of Excellence in Genomic Medicine Research, King Abdulaziz University, 21589, Jeddah, Kingdom of Saudi Arabia.

Associate Professor

Mohammad H. Al-Qahtani, Center of Excellence in Genomic Medicine Research, King Abdulaziz University, 21589, Jeddah, Kingdom of Saudi Arabia.

Professor

Published
2019-05-21
Section
Original Articles