FOXP3 deep intronic variant underlying IPEX

Area of Science:

• Genetics
• Immunology
• Molecular Biology

Background:

• Immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome is a rare, severe autoimmune disorder.
• The FOXP3 gene plays a critical role in immune system regulation.

Purpose of the Study:

• To report a novel deep intronic FOXP3 variant.
• To investigate the pathogenicity of this variant in a patient with IPEX syndrome.
• To analyze the variant's presence in heterozygous female carriers.

Main Methods:

• Whole exome sequencing was used to identify the genetic variant.
• RNA sequencing was performed on patient-derived cells and heterozygous female carriers.
• Functional analysis of the FOXP3 variant was conducted.

Main Results:

• A hemizygous deep intronic FOXP3 likely pathogenic variant (c.968-207A>G) was identified in the male IPEX patient.
• RNA sequencing revealed aberrant FOXP3 splicing in the patient.
• The variant was detected in heterozygous female carriers, indicating potential for altered gene expression.

Conclusions:

• The identified deep intronic FOXP3 variant is likely pathogenic and contributes to IPEX syndrome.
• RNA sequencing is a valuable tool for investigating deep intronic variants and their impact on gene expression.
• Understanding the carrier status is crucial for genetic counseling and family planning.