2023 ACMG Annual Clinical Genetics Meeting Digital Edition: Poster Gallery-WGS/WES as Unique Diagnostic Tool for the Genetic Screening of Patients with Craniosynostosis

Pdf Summary

The poster summarizes a study evaluating the use of whole-genome sequencing (WGS) and whole-exome sequencing (WES) as a diagnostic tool for genetic screening of patients with craniosynostosis (CS). CS is the premature closure of skull sutures, leading to craniofacial and neuropsychologic complications.<br /><br />The study included 59 patients with CS, specifically focusing on nonsyndromic forms of CS (NCS) which represent 70% of cases. WGS was performed in 54 cases, and WES in 5 cases. The samples were analyzed using an in-silico CS-related gene-panel and Human Phenotype Ontogeny (HPO)-driven analysis.<br /><br />The results showed that syndromic forms of CS (SCS) were present in 51% of the families, with multisuture synostosis being the most common type. Causal or potentially causal variants were detected in 38% of SCS cases. Variants of unknown clinical significance (VUSs) were detected in 87% of the remaining families, with an enrichment of variants in developmental genes, TGF-βeta pathway genes, and ciliopathy-related genes.<br /><br />The study highlights that WGS/WES can be a unique diagnostic tool for genetic screening in CS. It allows for customized analysis, starting with targeted in-silico analysis and progressing to wide genome/exome analysis, depending on the phenotypic presentation.<br /><br />The suggested diagnostic workflow in CS involves using WGS/WES to identify causal variants and potential therapeutic targets, which can aid in personalized treatment approaches for patients with CS.<br /><br />Overall, the study emphasizes the importance of genetic screening in CS and demonstrates the potential of WGS/WES as a valuable tool for accurate diagnosis and tailored treatment strategies.

Asset Subtitle

Presenting Author - Alexandra Topa, MD, PhD; Co-Author - Anna Rohlin, PhD; Co-Author - André Fehr, PhD; Co-Author - Lovisa Lovmar, MD, PhD; Co-Author - Göran Stenman, PhD; Co-Author - Peter Tarnow, MD, PhD; Co-Author - Giovanni Maltese, MD, PhD; Co-Author - Madiha Bhatti-Søfteland, MD, PhD; Co-Author - Lars Kölby, MD, PhD;

Meta Tag

Bone/Joint Abnormalities

Brain/Nervous System

Chromosomal Abnormalities

Dysmorphology

Etiology

Exome sequencing

Genome sequencing

Identification of Disease Genes

Malformation

Methodology

NextGen Sequencing

Phenotype

Phenotypic delineation of disorders

Sequencing

Co-Author Anna Rohlin, PhD

Co-Author André Fehr, PhD

Co-Author Lovisa Lovmar, MD, PhD

Co-Author Göran Stenman, PhD

Co-Author Peter Tarnow, MD, PhD

Co-Author Giovanni Maltese, MD, PhD

Co-Author Madiha Bhatti-Søfteland, MD, PhD

Co-Author Lars Kölby, MD, PhD

Presenting Author Alexandra Topa, MD, PhD

Keywords

whole-genome sequencing

whole-exome sequencing

diagnostic tool

genetic screening

craniosynostosis

skull sutures

nonsyndromic forms

syndromic forms

causal variants

therapeutic targets