{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nPRSS56 encodes a secreted, trypsin‐like serine protease that has emerged as a critical regulator of ocular development. Mutations in PRSS56 have been implicated in a spectrum of ocular conditions—including posterior microphthalmos, nanophthalmos, and angle‐closure glaucoma—by altering ocular axial length and the configuration of anterior segment structures. Disruption of PRSS56 function in mouse models leads to shortened ocular axes and malpositioning of the iridocorneal drainage tissues, thereby predisposing to elevated intraocular pressure."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nAt the molecular level, PRSS56 expression has been detected in key ocular tissues such as the retina, and its activity is crucial during a specific postnatal developmental window. Disease-associated mutations—including missense changes, frameshift mutations, and small duplications—are predicted to disrupt the catalytic properties of the enzyme by reducing its substrate affinity and reactivity. This loss of proteolytic function appears to impair the normal regulation of eye growth and axial length."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}, {"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nPopulation-based genetic studies have further elucidated the mutational spectrum of PRSS56. Multiple investigations—including whole-genome and exome sequencing analyses—have documented a variety of PRSS56 alleles, with some mutations, such as the recurrent c.1066dupC variant, acting as mutational hotspots with founder effects in certain populations. These studies reveal that PRSS56 mutations are frequently associated with more severe reductions in ocular axial length and distinct retinal–choroidal manifestations, thereby enhancing genotype–phenotype correlation insights."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "4", "end_ref": "9"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its role in regulating ocular size, functional studies have demonstrated that retina-derived PRSS56 is essential for the development and homeostasis of ocular drainage tissues. During a critical postnatal period, proper PRSS56 activity ensures the correct positioning of drainage structures, and its deficiency can lead to a posterior shift of these tissues, thereby impairing aqueous humor outflow and contributing to glaucoma pathogenesis. In support of this, rare PRSS56 variants have been identified in patients with primary congenital glaucoma, further underscoring the gene’s broad significance in maintaining intraocular pressure balance."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "10"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Andreas Gal, Isabella Rau, Leila El Matri, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Autosomal-recessive posterior microphthalmos is caused by mutations in PRSS56, a gene encoding a trypsin-like serine protease."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Hum Genet (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.ajhg.2011.02.006"}], "href": "https://doi.org/10.1016/j.ajhg.2011.02.006"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21397065"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21397065"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "K Saidas Nair, Mounira Hmani-Aifa, Zain Ali, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "Posterior microphthalmia and nanophthalmia in Tunisia caused by a founder c.1059_1066insC mutation of the PRSS56 gene."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Gene (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.gene.2013.06.045"}], "href": "https://doi.org/10.1016/j.gene.2013.06.045"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23820083"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23820083"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Congcong Guo, Zhenni Zhao, Denghui Chen, et al. 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