{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n Recent studies have identified CPAMD8—a gene encoding a C3 and PZP‐like alpha‑2‐macroglobulin domain–containing protein—as a key factor in ocular development. Mutations in CPAMD8 have been implicated in a spectrum of anterior segment disorders, including iris hypoplasia, ectopia lentis, corectopia, cataracts, and congenital glaucoma."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "6"}]}, {"type": "t", "text": " Studies in affected families have demonstrated that biallelic loss‐of‐function variants in CPAMD8 lead to structural abnormalities of the anterior chamber, with evidence from zebrafish models supporting a role in extracellular matrix organization during eye development.\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n In addition to its developmental functions, CPAMD8 is a novel member of the complement 3/alpha‑2‑macroglobulin family. Its molecular features include a signal peptide, an RXXR processing site, a thioester motif, and a C‑terminal Kazal‐type serine proteinase inhibitor domain; these characteristics suggest that CPAMD8 may participate in localized innate immune responses, with marked upregulation upon immune stimulation in cultured cells."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Furthermore, beyond its role in human ocular pathology, CPAMD8 variation has also been associated with congenital cataract phenotypes in cattle"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": "and identified as one of several candidate genes in genetically heterogeneous cases of primary congenital glaucoma."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": " These findings expand the potential impact of CPAMD8 variants on eye health and suggest that defects in this gene may contribute to overlapping clinical entities—including anterior segment dysgenesis, glaucoma, and lens abnormalities—possibly by affecting both developmental signaling and local immune modulation.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Sek-Shir Cheong, Lisa Hentschel, Alice E Davidson, et al. 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