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The association between GARRE1 (HGNC:29016) and primary myelofibrosis (MONDO_0009692) was initially suggested in a whole‑genome sequencing study of a primary myelofibrosis patient (PMID:23872309). In this study, GARRE1 emerged among several candidate genes that harbored somatic alterations in a patient carrying an MPL W515K mutation. The evidence from this single case report indicates that a candidate mutation in GARRE1 was detected, although no detailed variant description compliant with HGVS nomenclature was provided.
Genetic evidence remains limited as only one primary myelofibrosis patient (1 proband (PMID:23872309)) demonstrated a candidate change in GARRE1, and subsequent re‑sequencing in 178 patients with related myeloproliferative neoplasms failed to reveal recurrent variants. In addition, there was no segregation data reporting additional affected relatives carrying the variant.
The variant spectrum for GARRE1 is poorly defined in the provided studies. Without a compliant HGVS variant string for GARRE1, it is challenging to evaluate the mutation’s severity or its predicted impact on protein function. This paucity of recurrent genetic events diminishes the overall genetic evidence for GARRE1’s role in primary myelofibrosis.
Functional studies directly assessing the role of GARRE1 in the pathobiology of primary myelofibrosis were not reported. Although functional assays were performed for other candidate genes in the study, no experiments specifically evaluated GARRE1 expression, subcellular localization, or downstream effects in hematopoietic cells. This lack of experimental validation further limits independent support for a pathogenic mechanism involving GARRE1.
Integration of the limited genetic data with the absence of confirmatory experimental evidence results in a tentative association. In summary, while GARRE1 appears as a novel candidate gene observed in a primary myelofibrosis sample, the current evidence is insufficient for a robust clinical assertion and its utility in diagnostic decision‑making remains unproven.
Key take‑home: Further investigations, including targeted sequencing and functional validations, are necessary to clarify the role of GARRE1 in primary myelofibrosis and to establish its clinical relevance.
Gene–Disease AssociationLimitedA candidate mutation in GARRE1 was identified in a single primary myelofibrosis proband (PMID:23872309), but re‑sequencing in 178 cases did not reveal recurrent events. Genetic EvidenceLimitedGenetic data is derived from a lone case with no segregation or recurrent variant data, and no compliant HGVS variant description is available. Functional EvidenceLimitedNo direct functional studies or experimental assays were provided to support a role for GARRE1 in the disease mechanism. |