# Phenotypic Variability Associated with Jagunal Homolog 1 (JAGN1) Deficiency Caused by the c.63G>T Variant

## TL;DR

This study examines the varied symptoms and outcomes in patients with JAGN1 deficiency caused by a specific genetic variant, highlighting differences in clinical presentation and prognosis.

## Contribution

The study provides a detailed clinical characterization of JAGN1 deficiency caused by the c.63G>T variant in Romanian patients and compares it with literature cases.

## Key findings

- Patients with JAGN1 c.63G>T variant showed a wide range of symptoms, including neutropenia and infections.
- Most patients had a homozygous variant and consanguineous background, with a favorable prognosis in Romanian cases.
- No malignancy or leukemia was observed in patients during the follow-up period.

## Abstract

More than 30 distinct genetic entities associated with severe congenital neutropenia (SCN) have been described. SCN has a risk of clonal expansion of mutated hematopoietic cells. Jagunal homolog 1 (JAGN1) deficiency has been described as a genetic cause of SCN and is now estimated to account for approximately 10% of all SCN cases. One prevalent variant in patients with JAGN1 deficiency is NM_032492.4:c.63G>T (p.Glu21Asp). The clinical description and disease evolution study of Romanian patients with JAGN1 deficiency caused by the JAGN1 c.63G>T variant were performed together with a literature review of similar cases. The clinical characterization of six Romanian patients and nine additional patients reported in the literature with JAGN1 deficiency caused by the c.63G>T variant (40% female) revealed a wide phenotypic spectrum, including: neutropenia (all), severe infections (80%), developmental delay (13%), dental problems such as stomatitis/periodontitis (66%), and short stature (7%). No patient developed malignancy/leukemia during the follow-up period (15 ± 8.1 years). Most patients (93%) had a homozygous variant and consanguineous background, while one had compound heterozygous JAGN1 variants. The five Romanian patients carrying this homozygous variant, possibly due to a founder effect, had a relatively favorable clinical outcome, with good overall prognosis.