Prenatal genetic testing in 19 fetuses with corpus callosum abnormality

Abstract

Background Corpus callosum abnormality (CCA) can lead to epilepsy, moderate severe neurologic or mental retardation. The prognosis of CCA is closely related to genetic etiology. However, copy number variations (CNVs) associated with fetal CCA are still limited and need to be further identified. Only a few scattered cases have been reported to diagnose CCA by whole exome sequencing (WES). Methods Karyotyping analysis, copy number variation sequencing (CNV‐seq), chromosomal microarray analysis (CMA) and WES were parallelly performed for prenatal diagnosis of 19 CCA cases. Results The total detection rate of karyotyping analysis, CMA (or CNV‐seq) and WES were 15.79% (3/19), 21.05% (4/19) and 40.00% (2/5), respectively. Two cases (case 11 and case 15) were diagnosed as aneuploidy (47, XY, + 13 and 47, XX, + 21) by karyotyping analysis and CNV‐seq. Karyotyping analysis revealed an unknown origin fragment (46,XY,add(13)(p11.2)) in case 3, which was further confirmed to originate from p13.3p11.2 of chromosome 17 by CNV‐seq. CMA revealed arr1q43q44 (238923617–246964774) × 1(8.04 Mb) in case 8 with a negative result of chromosome karyotype. WES revealed that 2 of 5 cases with negative results of karyotyping and CNV‐seq or CMA carried pathogenic genes ALDH7A1 and ARID1B. Conclusion Parallel genetic tests showed that CNV‐seq and CMA are able to identify additional, clinically significant cytogenetic information of CCA compared to karyotyping; WES significantly improves the detection rate of genetic etiology of CCA. For the patients with a negative results of CNV‐seq or CMA, further WES test is recommended.

Molecular Approaches in Fetal Malformations, Dynamic Anomalies and Soft Markers: Diagnostic Rates and Challenges—Systematic Review of the Literature and Meta-Analysis

“…Concerning CNS, in a cohort of fetuses presenting isolated anomalies, the diagnostic rate was 45% [236]; while in another cohort of isolated and non-isolated CNS anomalies, the diagnostic rate was 50% [230]; and in a third cohort of fetuses presenting with isolated and not isolated cerebellar vermis defects and Dandy-Walker malformation, the diagnostic rate was 42% [98]. In two cohorts of fetuses presenting corpus callosum anomalies [227,228], the diagnostic rate scored 40% and 19%, whereas the VUS rate of 10% was reported in only one paper [228]. In a cohort of fetuses presenting isolated and non-isolated genitourinary anomalies, the diagnostic rate was 12% [235], whereas in another paper, the diagnostic rate was 7% [237].…”

Prenatal diagnosis of Coffin‐Siris syndrome: What are the fetal features?

“…She et al. detected two cases of monogenic conditions in five fetuses of isolated ACC without a causal anomaly on microarray, including one with a pathogenic ARID1B variant 10 . In our small series, 2/4 cases of CSS with ACC had an ARID1B variant.…”

“…9 causal anomaly on microarray, including one with a pathogenic ARID1B variant. 10 In our small series, 2/4 cases of CSS with ACC had an ARID1B variant. However, it seems that ACC is also common in other CSS-causing genes.…”

Additional diagnostic value of CNV‐seq over conventional karyotyping in prenatal diagnosis: A systematic review and meta‐analysis

“…The search identified 257 articles; 54 of these articles were reviewed fully, and 8 which met the final inclusion criteria were selected to be included in the meta-analysis. [12][13][14][15][16][17][18] Forty-six studies were excluded because their cases were less than 5, or focused on a certain chromosome abnormality, or full data unavailable. Table 1 summarized the characteristics of the studies included in the review including the first author, study period, content, gestational age et al All the studies were carried in China from 2013 to 2020.…”