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Journal article

Expanding Phenotype of GINS1 Deficiency: A Case Report and Review of the Literature

Abstract

ABSTRACT Pathogenic variants in GINS1 are believed to cause a primary combined immunodeficiency and growth retardation syndrome with natural killer cell deficiency and chronic neutropenia. To date, however, very few cases have been reported. Thus, the role of GINS1 in disease, as well as the spectrum of variants and their associated phenotype, remains unclear. We present a 2‐year‐old female with growth retardation, chronic neutropenia, distinctive facial features, and glaucoma. Exome sequencing revealed two likely pathogenic variants in GINS1 , c.‐48C>G p.? and c.247C>T p.Arg83Cys, conferring a diagnosis of GINS1 deficiency. She has overlapping features with the previously reported individuals, cementing growth retardation, neutropenia, and natural killer cell deficiency as core features. We additionally present a review of all nine individuals reported to date. We highlight that our proband, unlike the others, has no history of infections, and that glaucoma has now been observed in multiple unrelated individuals, pointing toward possible phenotypic expansion. Efforts to identify affected individuals, including those with different variants and phenotypes, are needed to understand ways in which GINS1 may be implicated in disease and the phenotypic spectrum of this ultrarare inborn error of immunity.

Authors

Mackley MP; Brager R; Geddie H; Breakey V; Hough R; Stavropoulos DJ; McNiven V

Journal

Clinical Genetics, , ,

Publisher

Wiley

Publication Date

February 13, 2026

DOI

10.1111/cge.70147

ISSN

0009-9163

Labels

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