Maternal Germline Mosaicism of a de Novo TUBB2B Mutation Leads to Complex Cortical Dysplasia in Two Siblings

Abstract

Introduction: Complex cortical dysplasia with other brain malformations-7 (a.k.a. polymicrogyria) caused by mutations in TUBB2B gene is a clinically heterogeneous condition. Case report: We report two siblings with polymicrogyria. Brain MRI showed polymicrogyria, small brainstem, thin corpus callosum and fused basal ganglia. Karyotypes and chromosomal microarray analysis were normal. By whole exome sequencing, there were a de novo variant of c.728C > T (p.P243L) in both siblings and a common single nucleotide polymorphism (SNP) (c.718C > T) in both siblings and the mother. Seminal DNA analysis obtained from father was normal. Conclusion: Maternal germline mosaicism was considered because the sequencing result of the father’s sperm was normal, two siblings had the same disease, and both patients and mother had the same SNP.

Keywords:

• Microtubules
• tubulin
• TUBB2B
• polymicrogyria
• germline mosaicism

Acknowledgments

Thanks to Assoc. Prof. Dr. Erkan GÖKÇE from Tokat Gaziosmanpaşa University Faculty of Medicine, Department of Radiology due to the help to the radiological evaluation of the patients and Dr. Hasan ŞİMŞEK from Diyarbakır Gazi Yaşargil Training and Research Hospital Department of Medical Genetics for his support in in-silico analysis and writing the article.

Declaration of interest statement

The authors report no conflicts of interest.