Inherited retinal diseases are clinically heterogeneous and are associated with nearly 300 different genes. In this retrospective, observational study of a consecutive cohort of 159 patients (134 families) with childhood‐onset (<16 years of age) retinal dystrophy, molecular investigations, and in‐depth phenotyping were performed to determine key clinical and molecular characteristics. The most common ocular phenotype was rod‐cone dystrophy in 40 patients. Leber Congenital Amaurosis, the most severe form of retinal dystrophy, was present in 10 patients, and early onset severe retinal dystrophy in 22 patients. Analysis has so far identified 131 pathogenic or likely pathogenic variants including 22 novel variants. Molecular diagnosis was achieved in 112 of 134 families (83.6%) by NGS gene panel investigation in 60 families, Sanger sequencing in 27 families, and Asper microarray in 25 families. An additional nine variants of uncertain significance were also found including three novel variants. Variants in 36 genes have been identified with the most common being ABCA4 retinopathy in 36 families. Five sporadic retinal dystrophy patients were found to have variants in dominant and X‐linked genes (CRX, RHO, RP2, and RPGR) resulting in more accurate genetic counseling of inheritance for these families. Variants in syndromic associated genes including ALMS1, SDCCAG8, and PPT1 were identified in eight families enabling directed systemic care.

中文翻译：

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新西兰队列的儿童期视网膜营养不良的分子和表型调查。

遗传性视网膜疾病在临床上是异质的，并且与近300种不同的基因有关。在此回顾性研究中，我们对连续队列的159例儿童发作（<16岁）视网膜营养不良的患者（134个家庭）进行了观察性研究，分子研究和深入的表型研究，以确定关键的临床和分子特征。40例患者中最常见的眼表型是视锥细胞营养不良。莱伯先天性阿莫罗病是最严重的视网膜营养不良形式，出现在10例患者中，早期发作的严重视网膜营养不良在22例患者中出现。迄今为止的分析已鉴定出131种病原体或可能的病原体变体，包括22种新的变体。通过对60个家庭的NGS基因小组调查，在134个家庭的112个家庭中进行了分子诊断（占83.6％），Sanger测序在27个家庭中进行，Asper芯片在25个家庭中进行。还发现了另外九个不确定性显着的变体，包括三个新颖的变体。已经鉴定出36个基因的变异，最常见的是36个家庭的ABCA4视网膜病变。发现五名散发性视网膜营养不良患者的显性基因和X连锁基因（CRX，RHO，RP2和RPGR）具有变异，从而为这些家族的遗传提供了更准确的遗传咨询。在八个家族中鉴定出与症状相关的基因的变异，包括ALMS1，SDCCAG8和PPT1，可以进行定向的系统护理。