# Case report: A case of novel homozygous LRBA variant induced by chromosomal segmental uniparental disomy - genetic and clinical insights

## TL;DR

A 2-year-old child with a rare genetic condition caused by a novel LRBA gene variant is reported, offering new insights into this rare disease.

## Contribution

This is the second global report of LRBA gene dysfunction caused by uniparental disomy and introduces a new pathogenic variant.

## Key findings

- The child had a homozygous LRBA gene variant c.2584C>T (p.Gln862Ter) due to paternal uniparental disomy.
- The variant was classified as 'Likely pathogenic' by ACMG guidelines and is not previously reported in literature.
- Clinical features included recurrent infections, neutropenia, and elevated IFN-α and IFN-r levels.

## Abstract

The study aims to report a rare case of a novel homozygous variant in the LRBA gene, originating from uniparental disomy of paternal origin. This case contributes new clinical data to the LRBA gene variant database.

The study details the case of a 2-year-old child diagnosed in May 2023 at our center with a homozygous LRBA gene variant. Detailed clinical data of the patient were collected, including whole-exome sequencing of peripheral blood mononuclear cells, with parental genetic verification.

The child presented with recurrent respiratory infections and chronic neutropenia, progressing to pancytopenia. Imaging showed splenomegaly and enlarged lymph nodes in the axillary and abdominal regions. Peripheral blood lymphocyte count revealed reduced B cells and NK cells. Elevated cytokine levels of IFN-α and IFN-r were observed. Whole-exome sequencing revealed a nonsense homozygous variant in the LRBA gene, specifically c.2584C>T (p.Gln862Ter). The father exhibited a heterozygous variant at this locus, while no variant was found in the mother. Sample analysis indicated characteristics of uniparental disomy. According to the guidelines of the American College of Medical Genetics and Genomics (ACMG), this variant is preliminarily classified as “Likely pathogenic”. Currently, there are no reports in academic literature regarding this specific variant site.

LRBA gene variants can lead to a rare inborn error of immunity disease. The c.2584C>T (p.Gln862Ter) variant in exon 22 of the LRBA gene is a newly identified pathogenic variant, and the homozygous variant caused by uniparental disomy is exceedingly rare. This case represents the second global report of an LRBA gene function loss due to uniparental disomy abnormalities.