Multi affected pedigree with congenital microcephaly: WES revealed PNKP gene mutation

Microcephaly is a rare neurological disorder, occurs in both isolated and syndromic forms. This classification could be confusing in rare disorders with variable phenotypic characteristics. However, identification of the causative gene through genetic study would allow determining the definite diagnosis. Here we reported a novel missense variant c.1133A>C (p.Lys378Thr) on the 13th exon of PNKP gene identified by whole exome sequencing (WES) in an Iranian multi-affected family with microcephaly, seizures and developmental delay (MCSZ) disorder. Data analysis suggested this variant as a pathogenic mutation which is co-segregate with the disease in the pedigree. PNKP gene mutation is consistent with the clinical features of the affected family members. Regarding both genetic findings and clinical examinations, the reported pedigree can be considered as another affected family with MCSZ syndrome, which has been reported about 10 cases worldwide. This study proves the application of WES for determining the final diagnosis in complicated neurodevelopmental disorders.