Analysis of TUBB2B gene variant in a fetus with complex cortical dysplasia with other brain malformations-7 / 中华医学遗传学杂志

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.

Analysis of non-invasive prenatal testing in 14 047 cases of advanced age pregnant women / 中华医学遗传学杂志

OBJECTIVE@#To assess the value of non-invasive prenatal testing (NIPT) for the diagnosis of fetal chromosomal aneuploidies among women with advanced gestational age.@*METHODS@#14 047 pregnant women have voluntarily accepted the NIPT test. The results of NIPT and amniocytic karyotyping analysis were compared, and the outcome of pregnancy was followed up.@*RESULTS@#NIPT has identified 104 cases with a high risk for trisomies 21, 18 and 13, and 44 cases with a high risk for sex chromosome abnormalities. After genetic consultation, 87 of 104 cases have accepted amniocyte chromosomal karyotyping. 63 cases of fetal chromosome abnormality were confirmed, including 46 cases of 21 trisomy, 11 cases of 18 trisomy and 6 cases of 13 trisomy. The positive predictive value was 83.64% (46/55), 61.11% (11/18), and 42.86% (6/14), the specificity was 99.93%, 99.95%, 99.94%, and the sensitivity was 100%. Among the 44 cases, 34 received amniocytic chromosomal karyotyping analysis, 11 cases were confirmed, the positive predictive value was only 32.35%. No aneuploidy was found in the low-risk cases. The negative predictive value was 100%.@*CONCLUSION@#As a prenatal screening method for women with advanced gestational age, NIPT has the highest positive predictive value for trisomy 21 and trisomy 18, but a lower positive predictive value for sex chromosome abnormalities. NIPT has a very low rate of missed diagnosis of trisomies 21, 18 and 13, which can significantly reduce the number of women undergoing invasive prenatal diagnosis.