A Novel UBA1 Gene Mutation in a Patient with Infantile Respiratory Distress Syndrome

Overview

Journal Hum Genome Var

Date 2025 Jan 6

PMID 39762237

Authors

Masafumi Miyata

Arisa Kojima

Yuri Kawai

Hidetoshi Uchida

Hiroko Boda

Naoko Ishihara

Hidehito Inagaki

Tetsushi Yoshikawa

Hiroki Kurahashi

Affiliations

Soon will be listed here.

Abstract

UBA1 is an E1 ubiquitin-activating enzyme that initiates the ubiquitylation of target proteins and is thus a key component of the ubiquitin signaling pathway. Three disorders are associated with pathogenic variants of the UBA1 gene: vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic (VEXAS) syndrome, lung cancer in never smokers (LCINS), and X-linked spinal muscular atrophy (XL-SMA, SMAX2). We here report a case of infantile respiratory distress syndrome followed by continuing neuromuscular symptoms. We identified a de novo hemizygous mutation, c.1660 C > T (p.Pro554Ser), in exon 15 of the UBA1 gene in this baby. This missense mutation was located with the AAD (active adenylation domain) of the protein, a known hotspot of SMAX2 mutations. This case lends support to the genotype-phenotype correlation regarding the UBA1 mutation and its related diseases.

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