Objective To perform prenatal diagnosis for a fetus with hydrocephalus and congenital heart disease by whole exome se-quencing ( WES) , and then provide genetic counseling for the next pregnancy. Methods DNAs from amniotic fluid cells of the fetus and peripheral blood of his/her parents were extracted, respectively, and then performed WES. After the process of library construc-tion, hybrid capture and sequencing, the obtained data were compared with the database from human genome and literatures and ana-lyzed by software. The pathogenic mutations were searched based on the American College of Medical Genetics and Genomics ( ACMG, 2015) guideline and verified by the Sanger sequencing. Results The WES results found that the compound heterozygous mutations ex-isted in POMT1 gene of the fetus, which were inherited from the splice site mutation c.605+1G>A( IVS7) of his/her mother and the frameshift mutation c.1367 c.1368 ( exon 15) insGA, p. L456Lfs?80 of his/her father, respectively. The Sanger sequencing results were consistent with that of WES. The fetus was affected by Walker-Warburg syndrome, and his/her parents decided to terminate the pregnancy finally. Conclusion The WES may diagnose Walker-Warburg syndrome rapidly and accurately, which may play an impor-tant role in clinical management and genetic counseling.

This article reported a case of pyruvate dehydrogenase E1-α deficiency suggested by abnormal brain development during prenatal ultrasound imaging. Prenatal ultrasound revealed a mild enlargement of bilateral cerebral ventricles and the possibility of intracranial hemorrhage in the fetus at 25 +1 weeks of gestation. MRI showed the fetus with absent corpus callosum, enlarged bilateral cerebral ventricles and paraventricular cysts. After genetic counseling and careful consideration, the couple opted for pregnancy termination. To clarify the cause of the disease, whole-exome sequencing was performed on the fetal skin to detect possible variants, and which revealed a frameshift mutation c.924_930dup(p.R311Gfs*5) in exon 10 of the PDHA1 gene. Sanger sequencing confirmed the mutation was a de novo pathogenic variant, indicating that the fetus was affected by pyruvate dehydrogenase E1-α deficiency.

OBJECTIVE: To explore the genetic basis for fetuses with renal anomalies. METHODS: Genomic DNA of four fetuses and their parents was extracted from amniotic fluid and peripheral blood samples and subjected to whole genome sequencing. Candidate variants were predicted according to the American College of Medical Genetics and Genomics (ACMG) guidelines and validated by SNP-array and Sanger sequencing. RESULTS: Two fetuses were found to carry a 1.45 Mb pathogenic microdeletion in 17q12 and a pathogenic 1.85 Mb microduplication at 1q21.1-21.2, respectively. One fetus was found to harbor compound heterozygous variants c.8301del (p.Asn2768Thrfs*18) and c.4481del (p.Asn1494Thrfs*6) of the PKHD1 gene, which were predicted to be pathogenic. And one fetus has harbored homozygous c.1372dup (p.Thr458Asnfs*5) variants of the BBS12 gene, which was predicted to be likely pathogenic. All variants were validated by Sanger sequencing. CONCLUSION Whole genome sequencing can enable efficient prenatal diagnosis for fetuses with renal anomalies with high accuracy.
Female ; Fetus/abnormalities* ; Humans ; Pregnancy ; Prenatal Diagnosis ; Whole Genome Sequencing