2023 ACMG Annual Clinical Genetics Meeting Digital Edition: Poster Gallery-Prenatal Detection of a Novel Pathogenic Missense Variant in <em>COL11A1 </em>Leads to a Familial Diagnosis of Stickler Syndrome Type II

Prenatal Detection of a Novel Pathogenic Missense Variant in COL11A1 Leads to a Familial Diagnosis of Stickler Syndrome Type II

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Pdf Summary

This study reports on the prenatal detection of a novel pathogenic missense variant in the COL11A1 gene, leading to a familial diagnosis of Stickler Syndrome Type II. The case involves a 36-year-old pregnant female who underwent an ultrasound at 18 weeks, revealing micrognathia in the fetus. Genetic counseling indicated a possible connective tissue disorder on the paternal side of the family, with symptoms including myopia, congenital cataracts, and retinal detachment. A custom genetic sequencing panel was performed, which identified a missense variant in COL11A1. Further segregation studies confirmed that the variant was pathogenic and caused Stickler Syndrome Type II in affected family members. The proband presented with lens subluxation, micrognathia/Pierre Robin sequence, and cleft palate at birth, confirming the diagnosis. The variant is located in a critical region of the protein and previous research has shown the importance of glycine residues in collagen formation. The evidence strongly supports the classification of the variant as likely pathogenic. The study highlights the importance of rapid follow-up familial testing after prenatal diagnosis, thorough genetic counseling, and deep phenotyping in identifying both prenatal and familial diagnoses of genetic disorders.

Asset Subtitle

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

Meta Tag

Clinical History

Genetic Testing

Genotype-Phenotype Correlations

Phenotype

Prenatal Diagnosis

Variant Detection

Co-Author Amiee B. Potter, PhD

Co-Author Sarah McCabe, B.S.

Co-Author Arpita Kulkarni, M.S.

Co-Author Sue Richards, PhD, FACMG

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

Presenting Author Timothy D. O'Brien, PhD

Keywords

prenatal detection

novel pathogenic missense variant

COL11A1 gene

Stickler Syndrome Type II

ultrasound

micrognathia

genetic counseling

connective tissue disorder

genetic sequencing panel

pathogenic variant