2023 ACMG Annual Clinical Genetics Meeting Digital Edition: Poster Gallery-Identification of Novel Variant in WT1 Gene in African-American Girl with Denys-Drash Syndrome

Pdf Summary

A novel variant in the WT1 gene has been discovered in a female of African-American descent with Denys-Drash Syndrome (DDS), a condition associated with Wilms tumor, congenital nephrotic syndrome, and XY pseudohermaphroditism in males. Wilms tumor is the most common renal tumor in children and is genetically heterogeneous, with a significant portion of cases linked to variants in the WT1 gene. The WT1 gene is responsible for encoding a protein involved in kidney cell growth and development. In this case, a de novo variant was found in the WT1 gene that has not been previously observed in large populations. The variant causes a frameshift mutation, resulting in a loss of gene function. The patient also had a risk allele in the APOL1 gene for end-stage renal disease and focal segmental glomerulosclerosis, as well as other variants of uncertain significance. The patient's clinical course included a diagnosis of Wilms tumor at a young age, nephrectomy, chemotherapy, radiation therapy, development of FSGS and chronic kidney disease, renal transplant, and subsequent diagnoses of renovascular hypertension, hypertriglyceridemia, insulin-dependent Type 2 Diabetes Mellitus, and anemia. This is the first report of the novel variant in the WT1 gene in a patient with Wilms tumor. Further studies may investigate the association of this variant with DDS and earlier onset of the disease.

Asset Subtitle

Presenting Author - Berrin Monteleone, MD; Co-Author - Meghan McGath, MS; Co-Author - Berrin Monteleone, MD;

Meta Tag

Cancer Syndromes

Cardiac/circulatory disorders

Chromosomal Abnormalities

Clinical Cytogenetics

Genitourinary malformations

Co-Author Meghan McGath, MS

Co-Author Berrin Monteleone, MD

Presenting Author Berrin Monteleone, MD

Keywords

WT1 gene

variant

African-American descent

Denys-Drash Syndrome

DDS

Wilms tumor

congenital nephrotic syndrome

XY pseudohermaphroditism

renal tumor

genetic heterogeneity