Overall, approximately one‐quarter of patients with genetic eye diseases will receive a molecular diagnosis. 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 month 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–phenotype relationships of these developmental eye disorders. In turn, this will lead to improved integrated care pathways, understanding of disease, and future therapeutic development.

中文翻译：

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英国非视网膜发育性眼病的分子诊断挑战。

总体而言，大约四分之一的遗传性眼病患者将接受分子诊断。患有发育性眼病的患者面临许多诊断挑战，包括显着不对称的表型异质性、眼部和全身性疾病共存、对人眼发育和相关遗传库的了解有限，以及无法获得被认为不会影响具有成本影响的患者结果/管理。在此，我们报告了我们在过去 12 个月内从儿科眼遗传学服务中获得的真实世界经验，其中包括来自 62 个家庭的 72 名连续患者，以及来自通过基因组学英格兰 100,000 基因组计划接受全基因组测序 (WGS) 的 322 名患者队列；包括小眼症、无眼症、眼缺损 (MAC)、眼前节发育不全异常 (ASDA)、原发性先天性青光眼、先天性白内障、婴儿眼球震颤和白化病。100,000 基因组计划招募的总体分子诊断率达到 24.9%（解决了 73/293 个家庭），但在临床环境中高达 33.9%（20/59 个家庭）。WGS 能够改善 MAC 患者 (15.7%) 的基因诊断，但不能改善 ASDA (15.0%) 和先天性白内障 (44.7%)。需要增加样本量和准确的人类表型本体 (HPO) 术语来提高诊断准确性。如果未应用正确的基因组，则显着的混合复杂眼表型会扭曲这些比率并导致遗漏变异。增加分子诊断将有助于解释这些发育性眼病的基因型-表型关系。反过来，