{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nAlthough some RNA‐binding proteins such as Brunol1 (a homolog of the elav/Bruno family) have been shown to be involved in post‐transcriptional processes and spermatogenesis without being critical for overall embryonic development (e.g., Brunol1 is expressed primarily in brain and testis and its loss leads to reduced sperm number and motility, yet preserves fertility)"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": ", recent investigations have focused on RSPRY1—a gene encoding a predicted protein with RING and SPRY domains. \n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nGenetic analyses in affected individuals from diverse populations have implicated biallelic loss‐of‐function or missense variants in RSPRY1 in a unique form of skeletal dysplasia. In one study, a homozygous frameshift mutation causing nonsense-mediated decay of RSPRY1 was identified in a consanguineous Saudi family, with subsequent identification of a similar phenotype in a Peruvian patient harboring a homozygous missense change. Expression studies revealed that RSPRY1 protein is strongly localized in murine embryonic osteoblasts and periosteal cells during primary endochondral ossification, supporting a direct role in bone development."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nAdditional clinical characterization of patients with RSPRY1 mutations, as reported in subsequent studies, has delineated a syndrome characterized by short stature, extremity deformities, facial dysmorphism, and intellectual disability. Radiological features include mild spondylar dysplasia, epimetaphyseal dysplasia of the long bones (often associated with coxa vara and genu valgum), brachymesophalangy with cone-shaped epiphyses, and craniosynostosis. These findings have established the entity known as Spondyloepimetaphyseal dysplasia Faden-Alkuraya type."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nFurther evidence solidifying the role of RSPRY1 in human skeletal development comes from reports of affected siblings bearing a homozygous missense variant, who not only manifested the described dysplastic features, but also exhibited joint dislocation—a novel clinical sign expanding the phenotypic spectrum of the disorder. Together, these studies underscore the importance of RSPRY1 in chondro-osseous development and highlight its crucial role in the pathogenesis of a distinct skeletal dysplasia."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Arvind Dev, Karim Nayernia, Moritz Meins, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Mice deficient for RNA-binding protein brunol1 show reduction of spermatogenesis but are fertile."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Reprod Dev (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/mrd.20742"}], "href": "https://doi.org/10.1002/mrd.20742"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17393433"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17393433"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Maha Faden, Fatema AlZahrani, Roberto Mendoza-Londono, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Identification of a Recognizable Progressive Skeletal Dysplasia Caused by RSPRY1 Mutations."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Hum Genet (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.ajhg.2015.08.007"}], "href": "https://doi.org/10.1016/j.ajhg.2015.08.007"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26365341"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26365341"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Pelin O Simsek-Kiper, Ekim Z Taskiran, Can Kosukcu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Further delineation of spondyloepimetaphyseal dysplasia Faden-Alkuraya type: A RSPRY1-associated spondylo-epi-metaphyseal dysplasia with cono-brachydactyly and craniosynostosis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Med Genet A (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/ajmg.a.40427"}], "href": "https://doi.org/10.1002/ajmg.a.40427"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30063090"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30063090"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Swati Singh, Hitesh Shah, Ashwin Dalal, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Two sisters with RSPRY1-related spondyloepimetaphyseal dysplasia."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Med Genet A (2024)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/ajmg.a.63601"}], "href": "https://doi.org/10.1002/ajmg.a.63601"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "38562122"}], "href": "https://pubmed.ncbi.nlm.nih.gov/38562122"}]}]}]}