A Twins Case of Lissencephaly With GPR56 Compound Heterozygous Mutations and Literatures Review

Abstract Background: Lissencephaly (LIS) is a malformation of cortical development characterized by developmental delay and seizure in combination with wide gyrus, superficial sulcus, and thickened cortex. Up to date, 20 genes have been implicated in LIS. However, GRP56-related LIS has never been reported, which was considered one causative gene for bilateral frontoparietal polymicrogyria(BFPP). Methods: Genetic testing of the proband was performed by whole exome sequencing and mainly analyzed 662 genes related to brain hypoplasia, white matter abnormalities, and hypothalamic-pituitary axis abnormalities such us AAAS, AARS2, ABAT, ABCC8, etc.. And the candidate mutations were further confirmed by polymerase chain reaction (PCR) and Sanger sequencing. Though we did genetic testing on the twin sisters and their parents, we could only obtain the clinical data of the older sister.Results: We reported a case of LIS twins, form a nonconsanguineous family, both carried the novel compound heterozygous GPR56 mutations, p.F76fs and p.H607fs.The older sister manifested lissencephaly, seizures, and flathead deformity and the younger sister had lissencephaly. We summarized their clinical characteristics and reviewed all the literatures of LIS and GPR56 to further clarify the correlation between genotype and phenotype.Conclusion: The LIS twins with GPR56 mutations were the first reported. By reviewing the clinical manifestations of LIS and GPR56 mutations, we validated the association between them, and broaden the clinical manifestations of GPR56 related phenotypes, indicating the importance of GPR56 screening in LIS patients.