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Updated: Jun 21, 2026
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Targeted Next-generation Sequencing and Bioinformatics Pipeline to Evaluate Genetic Determinants of Constitutional Disease
Published on: April 4, 2018
RNU4ATAC-opathy: Clinical, molecular, and transcriptomic insights from a large cohort
Dena R Matalon1, Angela L Duker2, Taylor M Arriaga3
1Division of Medical Genetics, Department of Pediatrics, Stanford University, Stanford, CA.
Summary
RNU4ATAC-opathy presents a wide spectrum of genetic and clinical features, including microcephaly and developmental delay. RNA sequencing aids in classifying variants and highlights challenges in detecting noncoding gene mutations.
Area of Science:
- Genetics
- Molecular Biology
- Clinical Medicine
Background:
- RNU4ATAC-related disorders are rare genetic conditions.
- Understanding the full spectrum of genotype and phenotype is crucial for diagnosis and management.
Purpose of the Study:
- To delineate the genotype-phenotype spectrum of RNU4ATAC-opathy.
- To assess the role of RNA sequencing in variant classification for this condition.
- To identify challenges in detecting variants within the noncoding RNU4ATAC gene.
Main Methods:
- Recruitment of 60 individuals with molecularly confirmed RNU4ATAC-opathy.
- Clinical and molecular data collection from international centers.
- RNA sequencing performed on seven affected individuals.
Main Results:
- Reported findings for 60 individuals, including 42 new cases and 33 distinct RNU4ATAC variants (13 novel).
- Identified core features: microcephaly, short stature, skeletal anomalies, developmental delay, cerebral anomalies, skin conditions, and immune deficiency.
- RNA sequencing revealed consistent minor intron retention and reclassified variants of uncertain significance to likely pathogenic in six cases.
Conclusions:
- RNU4ATAC-opathy exhibits significant variability in phenotypes and genotypes.
- Clinical laboratories must ensure robust analysis pipelines for noncoding genes like RNU4ATAC.
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