Detection of PLEKHG2 Mutation in Microcephaly: A Case Report

Introduction: Human microcephaly comprises a heterogeneous group of conditions that are characterized by afailure of normal brain growth. Congenital microcephaly is frequently inherited, usually as recessive traits, andare associated with mental retardation and sometimes epilepsy. Some of the genes are likely to control importantaspects of neural development in congenital microcephaly. Here, we present a family with congenitalmicrocephaly followed by molecular genetic evaluation.Methods: A seven-month old girl referred for genetic counselling after complete neurological assessment.Parents were first cousin and there was no history of similar disorder in their first and second degrees’ familymembers. Genomic DNA was evaluated through whole exome sequencing. Based on bioinformatics analysis ofcandidate variant, segregation study was done for parents and healthy child.Results: One homozygote variant, c.1448-2A> C, on PLEKHG2 gene has been detected. The frequencies of thisvariant in normal population are very low. It is predicted to be damaging by fathmm and Mutation Taster.PLEKHG2 -related Leukodystrophy and acquired microcephaly with or without dystonia. Disease is inherited inan autosomal recessive manner. Segregation analysis showed that parents and healthy child were heterozygotefor the variant.Conclusion: These findings strengthen the putative role of Next Generation Sequencing techniques inneurodevelopmental disorders. Although several candidate genes have been identified, this condition is clearlygenetically and clinically heterogeneous. More molecular assessment is needed to confirm the pathogenic effectof these variants on neurodevelopmental process.

Keywords:

Microcephaly , Neurogenetics , Next Generation Sequencing