TSC1 Mutations in Keratoconus Patients With or Without Tuberous Sclerosis

Area of Science:

• Genetics
• Ophthalmology
• Medical Research

Background:

• Tuberous sclerosis complex (TSC) is a genetic disorder.
• Bilateral keratoconus (KC) is an eye condition.
• Investigating shared genetic underpinnings between TSC and KC is crucial.

Purpose of the Study:

• To examine the TSC1 and TSC2 genes in a family with TSC and bilateral KC.
• To test if mutations in the same gene can cause both syndromic and nonsyndromic KC.
• To explore the genetic basis of KC in relation to TSC.

Main Methods:

• Next-generation sequencing and Sanger sequencing of TSC1 and TSC2 genes.
• Whole exome sequencing (WES) for nonsyndromic KC patients.
• RT-PCR for TSC1 expression analysis and in silico mutation modeling.

Main Results:

• A novel heterozygous nonsense TSC1 mutation was found in a patient with TSC and KC.
• Two heterozygous missense TSC1 variants were identified in patients with nonsyndromic KC.
• TSC1 gene expression was detected in both normal and KC corneas.

Conclusions:

• The TSC1 gene is implicated in both syndromic (TSC with KC) and nonsyndromic KC.
• Germline mutations in the TSC1 gene can lead to overlapping clinical features.
• This finding supports the hypothesis of diverse mutations in a single gene causing related disorders.