Prenatal exome sequencing in fetuses with callosal anomalies

• Published in: Prenatal diagnosis Vol. 42; no. 6; pp. 744 - 752
• Main Authors: Lei, Ting‐ying, She, Qin, Fu, Fang, Zhen, Li, Li, Ru, Yu, Qiu‐xia, Wang, Dan, Li, Ying‐si, Cheng, Ken, Zhou, Hang, Yang, Xin, Pan, Min, Li, Dong‐zhi, Liao, Can
• Format: Journal Article
• Language: English
• Published: England Wiley Subscription Services, Inc 01.05.2022
• Subjects: Anomalies; Children; Chromosomes; Diagnostic systems; DNA microarrays; Fetuses; Genetic diversity; Genetic variance; Prognosis
• ISSN: 0197-3851; 1097-0223; 1097-0223
• DOI: 10.1002/pd.6107

Objective We aimed to investigate the value of exome sequencing (ES) in fetuses with callosal anomalies (CA) with or without other structural anomalies, but with normal findings by karyotyping and chromosome microarray analysis (CMA). Methods Cases with CA with or without other structural anomalies were screened for eligibility. Fetuses with abnormal karyotyping or CMA results were excluded. We performed ES on DNA samples from eligible fetus‐parental trios and identified diagnostic genetic variants based on the ultrasonographic features. Results A total of 50 eligible fetus‐parental trios were successfully analyzed by ES. We found 17 likely pathogenic or pathogenic variants in 14 genes from 17 fetuses, with a total proportion of diagnostic genetic variants equal to 34.0% (17/50). Of the 17 cases with a diagnosis, 10 (29.4%, 10/35) were isolated and 7 (43.8%, 7/15) were non‐isolated. Pregnancy outcome data showed that 70.0% (7/10) of the surviving isolated CA fetuses with negative ES results had a good prognosis in early childhood. Conclusions Our study used ES prenatally for CA and showed that ES can be used diagnostically to define the molecular defects that underlie unexplained CA. Most subjects with isolated CA with negative results for genetic causes will have a favorable prognosis in early childhood. Key points What is already known on this topic? CNVs and monogenic causes have been shown to be associated with callosal anomalies (CA). Approximately 28.8%–50% of children with CA experienced general intellectual, academic, executive, social and/or behavioral difficulties and approximately 20%–71.2% were functioning at a level comparable to typically developing children. What does this study add? This study analyzed the use of exome sequencing (ES) in a group of fetuses with CA and the total proportion of diagnostic genetic variants was 34.0%. Most subjects with isolated CA with negative results for genetic causes will have a favorable prognosis in early childhood.