{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T16:14:19Z","timestamp":1790957659744,"version":"4.1.0"},"reference-count":74,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2020,9,30]],"date-time":"2020-09-30T00:00:00Z","timestamp":1601424000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Acta Ophthalmologica"],"published-print":{"date-parts":[[2021,6]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Purpose<\/jats:title>\n                    <jats:p>\n                      To (i) describe a series of patients with isolated or syndromic nanophthalmos with the underlying genetic causes, including novel pathogenic variants and their functional characterization and (ii) to study the association of retinal dystrophy in patients with\n                      <jats:italic>MFRP<\/jats:italic>\n                      variants, based on a detailed literature review of genotype\u2013phenotype correlations.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Patients with nanophthalmos and available family members received a comprehensive ophthalmological examination. Genetic analysis was based on whole\u2010exome sequencing and variant calling in core genes including\n                      <jats:italic>MFRP, BEST1, TMEM98, PRSS56, CRB1, GJA1, C1QTNF5, MYRF<\/jats:italic>\n                      and\n                      <jats:italic>FAM111A<\/jats:italic>\n                      . A minigene assay was performed for functional characterization of a splice site variant.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Seven patients, aged between three and 65\u00a0years, from five unrelated families were included. Novel pathogenic variants in\n                      <jats:italic>MFRP<\/jats:italic>\n                      (c.497C&gt;T, c.899\u20103C&gt;A, c.1180G&gt;A), and\n                      <jats:italic>PRSS56<\/jats:italic>\n                      (c.1202C&gt;A), and a recurrent de novo variant in\n                      <jats:italic>FAM111A<\/jats:italic>\n                      (c.1706G&gt;A) in a patient with Kenny\u2013Caffey syndrome type 2, were identified. In addition, we report co\u2010inheritance of\n                      <jats:italic>MFRP<\/jats:italic>\n                      \u2010related nanophthalmos and\n                      <jats:italic>ADAR<\/jats:italic>\n                      \u2010related Aicardi\u2013Gouti\u00e8res syndrome.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      Nanophthalmos is a genetically heterogeneous condition, and the severity of ocular manifestations appears not to correlate with variants in a specific gene. However, retinal dystrophy is only observed in patients harbouring pathogenic\n                      <jats:italic>MFRP<\/jats:italic>\n                      variants. Furthermore, heterozygous carriers of\n                      <jats:italic>MFRP<\/jats:italic>\n                      and\n                      <jats:italic>PRSS56<\/jats:italic>\n                      should be screened for the presence of high hyperopia. Identifying nanophthalmos as an isolated condition or as part of a syndrome has implications for counselling and can accelerate the interdisciplinary care of patients.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/aos.14615","type":"journal-article","created":{"date-parts":[[2020,9,30]],"date-time":"2020-09-30T08:10:54Z","timestamp":1601453454000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["Genotype\u2013phenotype spectrum in isolated and syndromic nanophthalmos"],"prefix":"10.1111","volume":"99","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0614-8669","authenticated-orcid":false,"given":"Elena","family":"Lang","sequence":"first","affiliation":[{"name":"Department of Ophthalmology University Hospital Zurich and University of Zurich Zurich Switzerland"},{"name":"Institute of Medical Molecular Genetics University of Zurich Schlieren 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