2023 ACMG Annual Clinical Genetics Meeting Digital Edition: Poster Gallery-RNASeq Analysis Identifies the Pathogenicity of Inherited Synonymous Splice-Region Variant in <em>NEB,</em> Confirming a Diagnosis of Neonatal Nemaline Myopathy 2

RNASeq Analysis Identifies the Pathogenicity of Inherited Synonymous Splice-Region Variant in NEB, Confirming a Diagnosis of Neonatal Nemaline Myopathy 2

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This article reports on a case study that used RNA sequencing (RNASeq) analysis and automated natural language processing (NLP) based phenotype review to confirm a diagnosis of neonatal nemaline myopathy 2 (NM2) in an infant. The case involved a two-day-old male infant with hypotonia, absent gag reflex, decreased muscle mass, and bilateral talipes equinovarus. Whole genome sequencing (WGS) identified two maternal variants and one paternal variant in the NEB gene, but their pathogenicity was uncertain. To further investigate, a muscle biopsy was performed, followed by RNASeq analysis, which provided evidence of altered splicing and nonsense-mediated decay of the paternal allele of NEB, confirming it as the pathogenic variant. Automated NLP-based phenotype review ruled out other potential gene candidates. This study highlights the value of combining RNASeq and automated NLP-based phenotype review to facilitate a molecular diagnosis when whole genome analysis is inconclusive. The authors also provide additional genomic and phenotype analysis data supporting their findings. Overall, this study demonstrates the utility of RNASeq analysis and automated NLP-based phenotype review in confirming the diagnostic status of putative splice-region variants in neonatal medical cases.

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Presenting Author - Barry Moore, MS; Co-Author - Thomas J. Nicholas; Co-Author - Rong Mao, MD; Co-Author - Brian J. Shayota, MD, MPH; Co-Author - Steven E. Boyden, PhD; Co-Author - Chelsea Solorzano, BSN, RN; Co-Author - Rachel Palmquist, MS, CGC; Co-Author - Pinar Bayrak-Toydemir; Co-Author - Katherine Noble, PHD; Co-Author - Andrew Farrell, PHD; Co-Author - Edgar J. Hernandez, PhD; Co-Author - Shawn Rynearson, BS; Co-Author - Carson Holt, PHD; Co-Author - Alistair N. Ward, MA, MSci, MS, PhD; Co-Author - Eric Fredrickson, PhD; Co-Author - Kelsey Nicholson, BS; Co-Author - David Pattison, MS; Co-Author - Jian M. Zhao, PhD; Co-Author - Makenzie L. Fulmer, PhD; Co-Author - Lucilla Pizzo, PhD; Co-Author - Ting Wen, PHD, MBBS; Co-Author - John M. O'Shea, PhD; Co-Author - Robert G. Lewis, PhD; Co-Author - Hayley M. Reynolds, BS; Co-Author - Betsy Ostrander, MD; Co-Author - Hunter Best, Ph.D.; Co-Author - Luca Brunelli, MD, PhD, FAAP; Co-Author - Mark Yandell, PhD; Co-Author - Gabor Marth, DSc; Co-Author - Aaron R. Quinlan, PhD; Co-Author - John C. Carey, MD; Co-Author - Martin Tristani-Firouzi, MD; Co-Author - Joshua L. Bonkowsky, MD; Co-Author - Sabrina Malone Jenkins, MD;

Meta Tag

Bioinformatics

Genetic Testing

Genome sequencing

Genomic Methodologies

Genotype-Phenotype Correlations

Identification of Disease Genes

NextGen Sequencing

Phenotype

Co-Author Thomas J. Nicholas

Co-Author Rong Mao, MD

Co-Author Brian J. Shayota, MD, MPH

Co-Author Steven E. Boyden, PhD

Co-Author Chelsea Solorzano, BSN, RN

Co-Author Rachel Palmquist, MS, CGC

Co-Author Pinar Bayrak-Toydemir

Co-Author Katherine Noble, PHD

Co-Author Andrew Farrell, PHD

Co-Author Edgar J. Hernandez, PhD

Co-Author Shawn Rynearson, BS

Co-Author Carson Holt, PHD

Co-Author Alistair N. Ward, MA, MSci, MS, PhD

Co-Author Eric Fredrickson, PhD

Co-Author Kelsey Nicholson, BS

Co-Author David Pattison, MS

Co-Author Jian M. Zhao, PhD

Co-Author Makenzie L. Fulmer, PhD

Co-Author Lucilla Pizzo, PhD

Co-Author Ting Wen, PHD, MBBS

Co-Author John M. O'Shea, PhD

Co-Author Robert G. Lewis, PhD

Co-Author Hayley M. Reynolds, BS

Co-Author Betsy Ostrander, MD

Co-Author Hunter Best, Ph.D.

Co-Author Luca Brunelli, MD, PhD, FAAP

Co-Author Mark Yandell, PhD

Co-Author Gabor Marth, DSc

Co-Author Aaron R. Quinlan, PhD

Co-Author John C. Carey, MD

Co-Author Martin Tristani-Firouzi, MD

Co-Author Joshua L. Bonkowsky, MD

Co-Author Sabrina Malone Jenkins, MD

Presenting Author Barry Moore, MS

Keywords

RNA sequencing

RNASeq analysis

automated natural language processing

NLP

neonatal nemaline myopathy 2

NM2

pathogenic variant

muscle biopsy

whole genome sequencing

phenotype review