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Patients with developmental eye disorders face a number of diagnostic challenges including phenotypic heterogeneity with significant asymmetry, coexisting ocular and systemic disease, limited understanding of human eye development and the associated genetic repertoire, and lack of access to next generation sequencing as regarded not to impact on patient outcomes\/management with cost implications. Herein, we report our real world experience from a pediatric ocular genetics service over a 12\u2009month period with 72 consecutive patients from 62 families, and that from a cohort of 322 patients undergoing whole genome sequencing (WGS) through the Genomics England 100,000 Genomes Project; encompassing microphthalmia, anophthalmia, ocular coloboma (MAC), anterior segment dysgenesis anomalies (ASDA), primary congenital glaucoma, congenital cataract, infantile nystagmus, and albinism. Overall molecular diagnostic rates reached 24.9% for those recruited to the 100,000 Genomes Project (73\/293 families were solved), but up to 33.9% in the clinic setting (20\/59 families). WGS was able to improve genetic diagnosis for MAC patients (15.7%), but not for ASDA (15.0%) and congenital cataracts (44.7%). Increased sample sizes and accurate human phenotype ontology (HPO) terms are required to improve diagnostic accuracy. The significant mixed complex ocular phenotypes distort these rates and lead to missed variants if the correct gene panel is not applied. Increased molecular diagnoses will help to explain the genotype\u2013phenotype relationships of these developmental eye disorders. In turn, this will lead to improved integrated care pathways, understanding of disease, and future therapeutic development.<\/jats:p>","DOI":"10.1002\/ajmg.c.31837","type":"journal-article","created":{"date-parts":[[2020,8,24]],"date-time":"2020-08-24T06:00:41Z","timestamp":1598248841000},"page":"578-589","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":49,"title":["Molecular diagnostic challenges for non\u2010retinal developmental eye disorders in the United Kingdom"],"prefix":"10.1002","volume":"184","author":[{"given":"Daniel","family":"Jackson","sequence":"first","affiliation":[{"name":"Moorfields Eye Hospital NHS Foundation Trust  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samantha","family":"Malka","sequence":"additional","affiliation":[{"name":"Moorfields Eye Hospital NHS Foundation Trust  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0763-3516","authenticated-orcid":false,"given":"Philippa","family":"Harding","sequence":"additional","affiliation":[{"name":"UCL Institute of Ophthalmology  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juliana","family":"Palma","sequence":"additional","affiliation":[{"name":"Moorfields Eye Hospital NHS Foundation Trust  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hannah","family":"Dunbar","sequence":"additional","affiliation":[{"name":"Moorfields Eye Hospital NHS Foundation Trust  London UK"},{"name":"UCL Institute of Ophthalmology  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1688-5360","authenticated-orcid":false,"given":"Mariya","family":"Moosajee","sequence":"additional","affiliation":[{"name":"Moorfields Eye Hospital NHS Foundation Trust  London UK"},{"name":"UCL Institute of Ophthalmology  London UK"},{"name":"Great Ormond Street Hospital for Children NHS Trust  London UK"},{"name":"The Francis Crick Institute  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,8,23]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1186\/1750-1172-7-8"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1155\/2016\/6341870"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.ede.0000158817.43037.ab"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1097\/ICU.0000000000000085"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/stem.2414"},{"key":"e_1_2_9_7_1","volume-title":"The National Genomics Research and Healthcare Knowledgebase v5","author":"Caulfield M.","year":"2019"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/cge.12275"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.31524"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2014.172"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmedgenet-2016-103837"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.31114"},{"key":"e_1_2_9_13_1","unstructured":"Genomics England Panel App. (n.d.). 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