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. TheASPM(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 theASPMgene 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 theASPMgene 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 theASPMgene underlying the disorder. The identified respective mutations were ruled out in 100 healthy control samples. In conclusion, we found three novel mutations in theASPMgene 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.