2023 ACMG Annual Clinical Genetics Meeting Digital Edition: Poster Gallery-Missense Variants and a Mild Non-lethal Form of TARP?

Pdf Summary

This article discusses the phenotypic spectrum of TARP syndrome, an X-linked recessive disorder characterized by a tetrad of diagnostic characteristics: Talipes equinovarus, Atrial septal defect, Robin sequence, and Persistent left superior vena cava. Early genetic reports associated this syndrome with truncating loss of function variants in the RBM10 gene and neonatal/early lethality. However, recent evidence suggests that there may be a milder non-lethal form of TARP syndrome lacking some of the originally described features. The severity of the syndrome appears to be influenced by the location and functional impact of the variant in the RBM10 gene.<br /><br />The article presents a case study of a 5-year-old male with global developmental delay, feeding difficulties, muscular hypotonia, and various craniofacial and skeletal anomalies. Whole exome sequencing identified a de novo novel missense variant in the RBM10 gene, which was determined to be likely pathogenic and causative of a mild form of TARP syndrome. The missense variant affected a critical functional domain of RBM10 involved in alternative splicing.<br /><br />The findings of this case support the idea that missense variants in RBM10 can cause a milder non-lethal form of TARP syndrome. These variants appear to broaden the clinical phenotype and mutational classes associated with the syndrome. The article also includes a table summarizing different RBM10 variants reported in TARP patients and their associated clinical features.<br /><br />Overall, this study highlights the importance of genetic testing in accurately diagnosing patients with TARP syndrome and understanding the spectrum of phenotypic variations associated with RBM10 variants.

Asset Subtitle

Presenting Author - Amiee B. Potter, PhD; Co-Author - Timothy D. O'Brien, PhD; Co-Author - Arpita Kulkarni, M.S.; Co-Author - Sarah McCabe, B.S.; Co-Author - Karen Kovak, M.S., CGC; Co-Author - Caleb Rogers, MD, FACMG; Co-Author - Sue Richards, PhD, FACMG; Co-Author - Stephen R. Moore, MBA, PHD, FACMG;

Meta Tag

Dysmorphology

Genetic Testing

Genotype-Phenotype Correlations

NextGen Sequencing

Phenotype

Sequencing

Variant Detection

Co-Author Timothy D. O'Brien, PhD

Co-Author Arpita Kulkarni, M.S.

Co-Author Sarah McCabe, B.S.

Co-Author Karen Kovak, M.S., CGC

Co-Author Caleb Rogers, MD, FACMG

Co-Author Sue Richards, PhD, FACMG

Co-Author Stephen R. Moore, MBA, PHD, FACMG

Presenting Author Amiee B. Potter, PhD

Keywords

TARP syndrome

phenotypic spectrum

X-linked recessive disorder

Talipes equinovarus

Atrial septal defect

Robin sequence

Persistent left superior vena cava

RBM10 gene

missense variant

alternative splicing