2023 ACMG Annual Clinical Genetics Meeting Digital Edition: Poster Gallery-Prenatal Diagnosis of a <em>RNU4ATAC</em>-Related Disorder Detected by Whole Genome Sequencing Not Seen by Exome Sequencing on the Initial Proband.

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This document discusses a case report of prenatal diagnosis of a RNU4ATAC-related disorder using whole genome sequencing (WGS) that was not detected by exome sequencing. The case involves two pregnancies affected by RNU4ATAC variants, resulting in recurrent anomalies. The prenatal phenotype of RNU4ATAC-related disorders may be characterized by unique central nervous system (CNS) anomalies, such as microcephaly, midline interhemispheric cysts, agenesis of the corpus callosum, and absent cavum septum pellucidum. The report also mentions potential extra-CNS findings, but they may be related to concomitant trisomy 21. Skeletal features may be less apparent prenatally compared to the postnatal phenotype.<br /><br />The limitations of exome sequencing in diagnosing cases involving noncoding RNA genes, like RNU4ATAC, are discussed, highlighting the superiority of WGS in such cases. WGS may also be effective in cases where a dual diagnosis is suspected. Genetic testing revealed compound heterozygous RNU4ATAC variants in the affected pregnancies.<br /><br />The report emphasizes the diagnostic challenge of prenatal diagnosis for RNU4ATAC-related disorders, as the variants cannot be captured by exome-based platforms, and the prenatal phenotype is still not well-defined. The use of WGS in this case identified the RNU4ATAC variants and demonstrated the diagnostic utility of WGS in prenatal diagnosis.<br /><br />Overall, this case report highlights the unique and variable ultrasound findings related to RNU4ATAC pathogenic variants and emphasizes the importance of WGS as a diagnostic tool in prenatal diagnosis for cases involving noncoding RNA genes. The outcome for both pregnancies in this case was pregnancy termination.

Asset Subtitle

Presenting Author - Lisa Pilchman, MS LCGC; Co-Author - Beverly Coleman, MD, FACR; Co-Author - Allan Fisher, MD, FACMG, FACOG; Co-Author - Natasha Combs, MS LCGC; Co-Author - Kendall Kaufmann, MS; Co-Author - Julie Moldenhauer, MD, FACOG, FACMG; Co-Author - ERICA MA. SCHINDEWOLF, MS, LCGC;

Meta Tag

Chromosomal Abnormalities

Exome sequencing

Fetal Pathology

Genetic Testing

Genome sequencing

Genotype-Phenotype Correlations

NextGen Sequencing

Phenotype

Prenatal Diagnosis

Sequencing

Ultrasound

Co-Author Beverly Coleman, MD, FACR

Co-Author Allan Fisher, MD, FACMG, FACOG

Co-Author Natasha Combs, MS LCGC

Co-Author Kendall Kaufmann, MS

Co-Author Julie Moldenhauer, MD, FACOG, FACMG

Co-Author ERICA MA. SCHINDEWOLF, MS, LCGC

Presenting Author Lisa Pilchman, MS LCGC

Keywords

prenatal diagnosis

RNU4ATAC-related disorder

whole genome sequencing

exome sequencing

prenatal phenotype

central nervous system anomalies

extra-CNS findings

trisomy 21

skeletal features

diagnostic challenge