Am J Med Genet A. 2025 Nov 5:e64299. doi: 10.1002/ajmg.a.64299. Online ahead of print.
ABSTRACT
Hypoparathyroidism, sensorineural deafness, and renal dysplasia (HDR) syndrome is caused by pathogenic variants in the GATA3 gene located on chromosome 10p14. Here we present a 10-year-old girl with HDR syndrome who also has oligoarticular juvenile idiopathic arthritis (JIA). The patient presented for genetics evaluation with bilateral sensorineural hearing loss, oligoarticular JIA, and a renal cyst. Trio-based exome sequencing and chromosome microarray analysis revealed a pathogenic heterozygous ~1.45 Mb deletion that included the entire GATA3 gene, consistent with a diagnosis of HDR syndrome. GATA3 is a risk locus associated with autoimmune disease, including rheumatoid arthritis; however, the link between protein-coding variants in GATA3 and autoimmune disease has not been well established. Previously, a single patient with HDR syndrome and psoriatic JIA was identified as having a frameshift variant in the GATA3 gene. These reports highlight the potential for increased susceptibility to early-onset autoimmune arthritis in HDR syndrome, expanding its phenotypic spectrum. Further studies are needed to investigate the role of pathogenic variants in the GATA3 gene in the pathogenesis of JIA and other autoimmune diseases.
PMID:41190486 | DOI:10.1002/ajmg.a.64299
