OBJECTIVE: To explore the genetic basis for a fetus with dysgenesis of corpus callosum and other brain malformations. METHODS: Whole exome sequencing was carried out for the fetus and its parents. Suspected pathogenic variants were verified by Sanger sequencing. RESULTS: A novel de novo missense variant c.758T>A (p.L253Q) of the TUBB2B gene was identified, which was unreported previously. Based on the guidelines from the American College of Medical Genetics, the c.758T>A variant was predicted to be likely pathogenic. Bioinformatics analysis predicted that the leucine at position 253 was highly conserved among various species, and the c.758T>A variant may impact the formation of hydrogen bonds between Leu253 and Asp249 and Met257 residues, which in turn may affect the combination of GTP/GDP and function of the TUBB2B protein. CONCLUSION The c.758T>A variant of the TUBB2B gene probably underlay the fetal malformations in this Chinese family. Above discovery has enriched the spectrum of TUBB2B gene variants and provided a basis for genetic counseling and prenatal diagnosis.
Brain ; Female ; Fetus/abnormalities* ; Humans ; Malformations of Cortical Development/genetics* ; Pregnancy ; Prenatal Diagnosis ; Tubulin/genetics* ; Whole Exome Sequencing