{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nRecent large‐scale genomic analyses in myelodysplastic syndromes (MDS) have focused on the 5q31.2 region, which contains 28 genes that, when haploinsufficient, may contribute to disease pathogenesis. In one study, systematic resequencing and copy‐number assessments revealed that point mutations or small deletions in these genes—including PROB1—are uncommon in MDS. Instead, the deletion typically results in a roughly 50% reduction in expression of multiple genes, suggesting that a combined decrease in gene dosage drives the disease phenotype."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn contrast, an independent investigation of an Ecuadorian family with keratoconus employed whole-exome sequencing to narrow down candidate variants within a linked region spanning 5q31.1–q35.3. In this study, a distinct missense variant (c.671G>A) in PROB1, along with variants in other genes, completely segregated with the keratoconus phenotype, indicating that PROB1 may be implicated in corneal development or structural integrity."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nCollectively, these findings suggest that while alterations in PROB1 do not appear to be key drivers in the context of MDS—where a broader haploinsufficiency of multiple 5q genes is observed—the identification of a segregating PROB1 variant in keratoconus highlights its potential tissue-specific role. Further functional studies are warranted to elucidate the precise biological mechanisms by which PROB1 contributes to corneal structure and how its dosage or mutational status might influence disease phenotypes across different clinical contexts."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": ""}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Timothy A Graubert, Michelle A Payton, Jin Shao, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Integrated genomic analysis implicates haploinsufficiency of multiple chromosome 5q31.2 genes in de novo myelodysplastic syndromes pathogenesis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS One (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pone.0004583"}], "href": "https://doi.org/10.1371/journal.pone.0004583"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19240791"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19240791"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Justyna A Karolak, Tomasz Gambin, Jose A Pitarque, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Variants in SKP1, PROB1, and IL17B genes at keratoconus 5q31.1-q35.3 susceptibility locus identified by whole-exome sequencing."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Eur J Hum Genet (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/ejhg.2016.130"}], "href": "https://doi.org/10.1038/ejhg.2016.130"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27703147"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27703147"}]}]}]}