The Turkish Journal of Pediatrics 2018 , Vol 60 , Num 3
GPR56 homozygous nonsense mutation p.R271* associated with phenotypic variability in bilateral frontoparietal polymicrogyria
Tülay Öncü-Öner 1 ,Aycan Ünalp 2 ,İlknur Porsuk-Doru 1 ,Sinem Ağılkaya 1 ,Handan Güleryüz 3 ,Aydan Saraç 4 ,Bekir Ergüner 5 ,Bayram Yüksel 4 ,Semra Hız-Kurul 6 ,Sultan Cingöz 1
1 Departments of Medical Biology and Genetics, Dokuz Eylül University Faculty of Medicine, İzmir, Turkey
2 Department of Pediatric Neurology, Dr. Behcet Uz Children’s Hospital, İzmir, Turkey
3 Departments of Pediatric Radiology, Dokuz Eylül University Faculty of Medicine, İzmir, Turkey
4 Genetic Engineering and Biotechnology Institute, TUBITAK Marmara Research Center
5 Advanced Genomics and Bioinformatics Research Center (İGBAM), The Scientific and Technological Research Council of Turkey (TUBITAK), BİLGEM, Kocaeli, Turkey
6 Departments of Pediatric Neurology, Dokuz Eylül University Faculty of Medicine, İzmir, Turkey
DOI : 10.24953/turkjped.2018.03.001 Öncü-Öner T, Ünalp A, Porsuk-Doru İ, Ağılkaya S, Güleryüz H, Saraç A, Ergüner B, Yüksel B, Hız-Kurul S, Cingöz S. GPR56 homozygous nonsense mutation p.R271* associated with phenotypic variability in bilateral frontoparietal polymicrogyria. Turk J Pediatr 2018; 60: 229-237.

Polymicrogyria is a disorder of neuronal migration characterized by excessive cortical folding and partially fused gyri separated by shallow sulci. Homozygous mutations in the GPR56 gene, which regulates migration of neural precursor cells, are associated with bilateral frontoparietal polymicrogyria (BFPP) syndrome including white matter changes, brainstem and cerebellar involvement. Herein, we describe three siblings of consanguineous parents with a homozygous germline mutation (p.R271*) located in the seventh exon of the GPR56 gene that was previously detected in only one Portuguese patient. Phenotypic/genotypic relationships were analysed according to the clinical characteristics in only index patient. While earlier reported patient was exhibiting seizures provoked by hot water, macrocephaly, cerebellar/brainstem hypoplasia and corpus callosum abnormalities, the index patient showed only hypoplasia of brainstem, focal onset bilateral tonic clonic seizure. Despite the phenotypic similarities in two patients, the potential causes of the variation in the expression of the p.R271* variant between the two affected families might be genetic or epigenetic factors beyond the GPR56 gene. Consequently, the present findings show that the same mutation in GPR56 gene can have different phenotypic effects. Therefore, additional functional studies are needed to detect the phenotypic spectrum of the p.R271* mutation in GPR56, and provide insight into the mechanism of normal cortical development and regional patterning of the cerebral cortex. Keywords : BFPP, GPR56 mutations, polymicrogyria, whole exome sequencing

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