Hereditary ophthalmic pathology is a genetically heterogeneous group of diseases that occur either as an isolated eye disorder or as a symptom of hereditary syndromes (chromosomal or monogenic). Thus, a diagnostic search in some cases of ophthalmic pathology can be time- and cost-consuming. The most challenging situation can arise when prenatal diagnosis is needed during an ongoing pregnancy. A family was referred to the Research Centre for Medical Genetics (RCMG) for childbirth risk prognosis at 7–8 week of gestation because a previous child, a six-year-old boy, has congenital aniridia, glaucoma, retinal detachment, severe psychomotor delay, and lack of speech and has had several ophthalmic surgeries. The affected child had been previously tested for PAX6 mutations and 11p13 copy number variations, which revealed no changes. Considering the lack of pathogenic changes and precise diagnosis for the affected boy, NGS sequencing of clinically relevant genes was performed for the ongoing pregnancy; it revealed a novel hemizygous substitution NM_000266.3(NDP):c.385G > T, p.(Glu129*), in the NDP gene, which is associated with Norrie disease (OMIM #310600). Subsequent Sanger validation of the affected boy and his mother confirmed the identified substitution inherited in X-linked recessive mode. Amniotic fluid testing revealed the fetus was hemizygous for the variant and lead to the decision of the family to interrupt the pregnancy. Complications which developed during the termination of pregnancy required hysterectomy due to medical necessity. Clinical polymorphism of hereditary ophthalmic pathology can severely complicate establishment of an exact diagnosis and make it time- and cost-consuming. NGS appears to be the method-of-choice in complicated cases, and this could substantially hasten the establishment of a diagnosis and genetic risk estimation.

中文翻译：

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在持续妊娠期间对受影响的先证者进行完整的外显子测序后，对诺里病进行产前诊断：病例报告

遗传性眼科病理学是遗传上异质的一组疾病，它们以孤立的眼部疾病或遗传综合征（染色体或单基因）的症状出现。因此，在某些眼科病理学情况下进行诊断搜索可能既费时又费钱。当持续妊娠期间需要进行产前诊断时，可能会出现最具挑战性的情况。一个家庭在妊娠7-8周时被转交给医学遗传学研究中心（RCMG）进行分娩风险预后，因为前一个孩子（六岁的男孩）患有先天性无虹膜，青光眼，视网膜脱离，严重的精神运动延迟，并且缺乏言语，并且接受过多次眼科手术。患病的孩子先前已经接受过PAX6突变和11p13拷贝数变异的测试，结果没有变化。考虑到患病男孩缺乏病原学变化和精确诊断，对正在进行的妊娠进行了临床相关基因的NGS测序。它揭示了一种新的半合子取代NM_000266.3（NDP）：c.385G> T，p。（Glu129 *），与Norrie病（OMIM＃310600）有关。随后对患病男孩及其母亲进行的桑格（Sanger）验证证实了在X连锁隐性模式下遗传的替代基因。羊水测试显示，胎儿是该变异体的半合子，并导致家庭决定中断妊娠。由于医学上的需要，在妊娠终止期间发生的并发症需要子宫切除术。遗传性眼科病理的临床多态性会使建立准确的诊断严重复杂化，并使其既费时又费钱。NGS似乎是复杂情况下的首选方法，这可以大大加快诊断和遗传风险评估的速度。