Faculty, Staff and Student Publications

Language

English

Publication Date

3-1-2026

Journal

Molecular Genetics & Genomic Medicine

DOI

10.1002/mgg3.70205

PMID

41721485

PMCID

PMC12927969

PubMedCentral® Posted Date

2-20-2026

PubMedCentral® Full Text Version

Post-print

Abstract

Background: Tuberous sclerosis complex (TSC) is an autosomal dominant genetic disorder characterized by the formation of hamartomas in the brain, kidney, and heart, along with other complex clinical manifestations, including TSC-associated neuropsychiatric disorder (TAND). Development of genotype-phenotype correlations within TSC can aid clinicians in providing prognostic data and improve clinical management. We present here a multigenerational family who has a pathogenic variant in TSC2 displaying a severe renal phenotype.

Methods: A 23-year-old Caucasian male (Patient 1) was determined to have a molecularly confirmed diagnosis of TSC at approximately 2 months of age. The nonsense pathogenic variant (c.1372C>T (p.Arg458*)) in TSC2 had been previously identified in his father (Patient 6), grandmother (Patient 5), and other extended paternal family members (Patient 2, 3, 4, 7).

Results: Clinical evaluations revealed that the affected family members display a severe renal phenotype characterized by large angiomyolipoma burden (AMLs), renal cystic disease, and chronic kidney disease leading to renal failure.

Conclusion: Our clinical report is of significance as it illustrates a possible genotype-phenotype correlation between a specific TSC2 pathogenic variant and a severe renal phenotype. Our case series highlights the importance of establishing genotype-phenotype interactions to provide anticipatory guidance using prognostic data and clinical management.

Keywords

Humans, Male, Tuberous Sclerosis, Tuberous Sclerosis Complex 2 Protein, Phenotype, Young Adult, Pedigree, Adult, Female, Angiomyolipoma, ngiomyolipoma, kidney, pathogenic variant, TSC2, tuberous sclerosis complex

Published Open-Access

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