Seyedeh Sedigheh Abedini - Genetics Research Center, University of Social Welfare & Rehabilitation Sciences, Tehran, Iran
Luciana Musante - Department of Human Molecular Genetics, Max-Planck Institute for Molecular Genetics, Berlin, Germany.
Hao Hu - Department of Human Molecular Genetics, Max-Planck Institute for Molecular Genetics, Berlin, Germany.
Masoumeh Hosseini - Genetics Research Center, University of Social Welfare & Rehabilitation Sciences, Tehran, Iran.

Introduction: Autosomal recessive primary microcephaly (MCPH) is a congenital disorder caused by impaired neurogenic mitosis lead to defect in brain development. This disorder is heterogeneous genetically and characterized by reduced head circumference (-2 SD or more) under age and sex-based mean and mild to severe intellectual disability.So far, 12 genetic loci (MCPH1-12) with twelve corresponding genes (MCPH1, WDR62, CDK5RAP2, CASC5, ASPM,CENPJ, STIL, CEP135, CEP152, ZNF335, PHC1 and CDK6) have been identified for this disease. Using whole-exomesequencing (WES) as a new pioneer technology and diagnostic tool, we can provide an opportunity for identifying the causal mutations with more efficient and cost-effectiveness in Iranian patients with autosomal recessive primary microcephaly. Case presentation: We report an Iranian family with two affected individuals with moderate intellectual disability, large toes and primary microcephaly with consanguineous marriage. We performed WES for one affected and focused on genesassociated with microcephaly and homozygous variants. We identified a homozygous novel frameshift mutation inCDK5RAP2 in the affected individual. Sanger sequencing confirmed the presence of the homozygous mutation in the other affected and heterozygous state for parents and normal siblings. Discussion: WES led to cost-effectiveness and rapid identification of novel frameshift deletion in CDK5RAP2 in Iranianfamily with primary microcephaly. We can facilitate genetic counseling for this family. To date, only five different mutations have been reported for CDK5RAP2 gene which most of them were from Pakistan. Moreover, this study implies that WES is a suitable diagnostic tool for identifying mutations responsible for MCPH families.

Primary Microcephaly, CDK5RAP2, Whole exome sequencing, Iranian family