Whole Exome Sequencing Identifies Three Novel Mutations in the ASPM Gene From Saudi Families Leading to Primary Microcephaly

Frontiers in Pediatrics

Hiba Alkhatabi¹  Angham Abdulrahman Abdulkareem²  Muhammad Imran Naseer³  Adeel G. Chaudhary⁴  Sameera Sogaty⁵  Sarah Almaghrabi⁶  Osama Yousef Muthaffar⁷ 

[1] Center of Excellence in Genomic Medicine Research, King Abdulaziz University, Jeddah, Saudi Arabia;College of Applied Medical Sciences, King Abdulaziz University, Jeddah, Saudi Arabia;Center of Excellence in Genomic Medicine Research, King Abdulaziz University, Jeddah, Saudi Arabia;Department of Biochemistry, Faculty of Science, King Abdulaziz University, Jeddah, Saudi Arabia;Center of Excellence in Genomic Medicine Research, King Abdulaziz University, Jeddah, Saudi Arabia;Department of Medical Laboratory Technology, Faculty of Applied Medical Sciences, King Abdulaziz University, Jeddah, Saudi Arabia;Center of Excellence in Genomic Medicine Research, King Abdulaziz University, Jeddah, Saudi Arabia;Department of Medical Laboratory Technology, Faculty of Applied Medical Sciences, King Abdulaziz University, Jeddah, Saudi Arabia;Center for Innovation in Personalized Medicine, King Abdulaziz University, Jeddah, Saudi Arabia;Department of Medical Genetics, King Fahed General Hospital, Jeddah, Saudi Arabia;Department of Medical Laboratory Technology, Faculty of Applied Medical Sciences, King Abdulaziz University, Jeddah, Saudi Arabia;Center for Innovation in Personalized Medicine, King Abdulaziz University, Jeddah, Saudi Arabia;Department of Pediatrics, King Abdulaziz University, Jeddah, Saudi Arabia;

关键词: ASPM;    primary microcephaly;    whole exom sequencing;    Saudi population;    MCPH;   

DOI  :  10.3389/fped.2020.627122

来源: Frontiers

【 摘 要 】

Autosomal recessive primary microcephaly (MCPH) is a neurodevelopmental defect that is characterized by reduced head circumference at birth along with non-progressive intellectual disability. Till date, 25 genes related to MCPH have been reported so far in humans. The ASPM (abnormal spindle-like, microcephaly-associated) gene is among the most frequently mutated MCPH gene. We studied three different families having primary microcephaly from different regions of Saudi Arabia. Whole exome sequencing (WES) and Sanger sequencing were done to identify the genetic defect. Collectively, three novel variants were identified in the ASPM gene from three different primary microcephaly families. Family 1, showed a deletion mutation leading to a frameshift mutation c.1003del. (p.Val335*) in exon 3 of the ASPM gene and family 2, also showed deletion mutation leading to frameshift mutation c.1047del (p.Gln349Hisfs*18), while in family 3, we identified a missense mutation c.5623A>G leading to a change in protein (p.Lys1875Glu) in exon 18 of the ASPM gene underlying the disorder. The identified respective mutations were ruled out in 100 healthy control samples. In conclusion, we found three novel mutations in the ASPM gene in Saudi families that will help to establish a disease database for specified mutations in Saudi population and will further help to identify strategies to tackle primary microcephaly in the kingdom.

【 授权许可】

CC BY