Yan Lulu, Lu Zhaier, Liu Yingwen, Han Chunxiao, Ying Hongjun, Bao Youwei, Xue Jiangyang, Li Haibo
The Central Laboratory for Birth Defect Prevention and Control, Ningbo Women and Children's Hospital Zhejiang 315012, China.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi. 2022 Mar 10;39(3):301-304. doi: 10.3760/cma.j.cn511374-20210331-00285.
To explore the genetic basis for a fetus with dysgenesis of corpus callosum and other brain malformations.
Whole exome sequencing was carried out for the fetus and its parents. Suspected pathogenic variants were verified by Sanger sequencing.
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.
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.
探讨一名患有胼胝体发育不全及其他脑畸形胎儿的遗传基础。
对该胎儿及其父母进行全外显子组测序。通过桑格测序验证疑似致病变异。
鉴定出TUBB2B基因一个新的从头错义变异c.758T>A（p.L253Q），此前未见报道。根据美国医学遗传学学会的指南，预测c.758T>A变异可能致病。生物信息学分析预测，253位的亮氨酸在不同物种间高度保守，c.758T>A变异可能影响Leu253与Asp249和Met257残基之间氢键的形成，进而可能影响GTP/GDP的结合及TUBB2B蛋白的功能。
TUBB2B基因的c.758T>A变异可能是这个中国家系中胎儿畸形的病因。上述发现丰富了TUBB2B基因变异谱，为遗传咨询和产前诊断提供了依据。
