Department of Ophthalmology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
Department of Ophthalmology, Hirosaki University Graduate School of Medicine, Hirosaki, Japan.
Ophthalmic Genet. 2023 Oct;44(5):423-429. doi: 10.1080/13816810.2023.2208220. Epub 2023 Jul 28.
Nanophthalmos (NNO) is a rare condition with significantly shorter axial length than normal. Several genes are known to cause NNO, among them the MFRP and PRSS56 genes have been reported to cause majority of NNOs. The purpose of this study was to determine the genetic basis of Japanese patients with NNO.
We studied seven patients with NNO. Whole exome sequencing (WES) and Sanger sequencing were performed to determine the variants causing the NNO. We also reviewed the medical charts of the patients to determine the phenotype of these seven patients.
WES revealed that four patients from three families carried homozygous frameshift variants of the PRSS56 gene (c.1066dupC). Two novel variants of the MFRP gene were detected in the other two patients: one proband had a homozygous missense variant (c.1486 G>A) and the other had a compound heterozygous variant (c.1486 G>A and c.662_663insT). The axial length of the eight eyes with the PRSS56 variant was 15.69 ± 0.48 mm (mean ± SD) and that for the 4 eyes with the MFRP variant was 15.63 ± 0.69 mm. Three of the six cases with the PRSS56 or MFRP variant had the uveal effusion syndrome.
NNOs in Japanese patients are caused by variants of the PRSS56 and MFRP genes as in other ethnic populations. In addition, two new variants of the MFRP gene were found in our cohort. The phenotypes and anomalies in Japanese patients with NNO were similar to those reported for other ethnic populations.
先天性眼球小症（NNO）是一种罕见病症，其眼轴长度明显短于正常水平。已知有几个基因会导致 NNO，其中 MFRP 和 PRSS56 基因已被报道是导致大多数 NNO 的原因。本研究旨在确定日本 NNO 患者的遗传基础。
我们研究了 7 名 NNO 患者。进行了全外显子组测序（WES）和 Sanger 测序，以确定导致 NNO 的变异。我们还回顾了患者的病历，以确定这 7 名患者的表型。
WES 显示，来自 3 个家庭的 4 名患者携带 PRSS56 基因的纯合移码变异（c.1066dupC）。在另外两名患者中检测到 MFRP 基因的两个新变异：一名先证者携带纯合错义变异（c.1486G>A），另一名携带复合杂合变异（c.1486G>A 和 c.662_663insT）。8 只携带 PRSS56 变异的眼睛的眼轴长度为 15.69±0.48mm（平均值±标准差），而 4 只携带 MFRP 变异的眼睛的眼轴长度为 15.63±0.69mm。在 6 例 PRSS56 或 MFRP 变异中，有 3 例伴有葡萄膜积液综合征。
日本 NNO 患者的 NNO 是由 PRSS56 和 MFRP 基因的变异引起的，与其他种族群体相同。此外，在我们的队列中发现了 MFRP 基因的两个新变异。日本 NNO 患者的表型和异常与其他种族群体报告的相似。
