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These conditions are manifested by the absence of an eye or reduced eye volumes within the orbit leading to vision loss. Although clinical case series suggest a strong genetic component in A\/M, few systematic investigations have been conducted on potential genetic contributions owing to low population prevalence. To overcome this challenge, we utilized DNA samples and data collected as part of the National Birth Defects Prevention Study (NBDPS). The NBDPS employed multi\u2010center ascertainment of infants affected by A\/M. We performed exome sequencing on 67 family trios and identified numerous genes affected by rare deleterious nonsense and missense variants in this cohort, including <jats:italic>de novo<\/jats:italic> variants. We identified 9 nonsense changes and 86 missense variants that are absent from the reference human population (Genome Aggregation Database), and we suggest that these are high priority candidate genes for A\/M. We also performed literature curation, single cell transcriptome comparisons, and molecular pathway analysis on the candidate genes and performed protein structure modeling to determine the potential pathogenic variant consequences on PAX6 in this disease.<\/jats:p>","DOI":"10.1002\/ajmg.a.62874","type":"journal-article","created":{"date-parts":[[2022,6,18]],"date-time":"2022-06-18T08:33:49Z","timestamp":1655541229000},"page":"2376-2388","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Exome sequencing identifies genetic variants in anophthalmia and microphthalmia"],"prefix":"10.1002","volume":"188","author":[{"given":"Jingjing","family":"Li","sequence":"first","affiliation":[{"name":"Department of Neurology School of Medicine, The Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, The Bakar Computational Health Sciences Institute, The Parker Institute for Cancer Immunotherapy University of California San Francisco  San Francisco California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Stanford University School of Medicine  Stanford California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuejun Jessie","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Neurology School of Medicine, The Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, The Bakar Computational Health Sciences Institute, The Parker Institute for Cancer Immunotherapy University of California San Francisco  San Francisco California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chen","family":"Ma","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Stanford University School of Medicine  Stanford California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cynthia J.","family":"Curry","sequence":"additional","affiliation":[{"name":"Genetic Medicine, Department of Pediatrics University of California  San Francisco California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"McGoldrick","sequence":"additional","affiliation":[{"name":"Department of Genome Sciences University of Washington  Seattle Washington USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deborah A.","family":"Nickerson","sequence":"additional","affiliation":[{"name":"Department of Genome Sciences University of Washington  Seattle Washington USA"},{"name":"Brotman Baty Institute for Precision Medicine  Seattle Washington USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica X.","family":"Chong","sequence":"additional","affiliation":[{"name":"Brotman Baty Institute for Precision Medicine  Seattle Washington USA"},{"name":"Division of Genetic Medicine, Department of Pediatrics University of Washington  Seattle Washington USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth E.","family":"Blue","sequence":"additional","affiliation":[{"name":"Brotman Baty Institute for Precision Medicine  Seattle Washington USA"},{"name":"Division of Medical Genetics, Department of Medicine University of Washington  Seattle Washington USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James C.","family":"Mullikin","sequence":"additional","affiliation":[{"name":"National Human Genome Research Institute, National Institutes of Health  Bethesda Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennita","family":"Reefhuis","sequence":"additional","affiliation":[{"name":"National Center on Birth Defects and Developmental Disabilities Centers for Disease Control and Prevention  Atlanta Georgia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wendy N.","family":"Nembhard","sequence":"additional","affiliation":[{"name":"Department of Epidemiology Fay W. 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