Tachibana Nobutaka, Hosono Katsuhiro, Nomura Shuhei, Arai Shinji, Torii Kaoruko, Kurata Kentaro, Sato Miho, Shimakawa Shuichi, Azuma Noriyuki, Ogata Tsutomu, Wada Yoshinao, Okamoto Nobuhiko, Saitsu Hirotomo, Nishina Sachiko, Hotta Yoshihiro
Department of Ophthalmology, Hamamatsu University School of Medicine, Hamamatsu 431-3192, Japan.
Department of Pediatrics, Osaka Medical and Pharmaceutical University Hospital, Takatsuki 569-8686, Japan.
Genes (Basel). 2022 Feb 16;13(2):359. doi: 10.3390/genes13020359.
Uniparental disomy (UPD) is a rare chromosomal abnormality. We performed whole-exosome sequencing (WES) in cases of early-onset retinal dystrophy and identified two cases likely caused by UPD. Herein, we report these two cases and attempt to clarify the clinical picture of retinal dystrophies caused by UPD.
WES analysis was performed for two patients and their parents, who were not consanguineous. Functional analysis was performed in cases suspected of congenital disorders of glycosylation (CDG). We obtained clinical case data and reviewed the literature.
In case 1, a novel c.57G>C, p.(Trp19Cys) variant in was detected homozygously. Genetic analysis suggested a maternal UPD on chromosome 4, and functional analysis confirmed CDG. Clinical findings showed early-onset retinal dystrophy, intellectual disability, and epilepsy. In case 2, an Alu insertion (c.4052_4053ins328, p.[Tyr1352Alafs]) in was detected homozygously. Maternal UPD on chromosome 8 was suspected. The clinical picture was consistent with -related retinitis pigmentosa. Although the clinical features of retinal dystrophy by UPD may vary, most cases present with childhood onset.
There have been limited reports of retinal dystrophy caused by UPD, suggesting that it is rare. Genetic counseling may be encouraged in pediatric cases of retinal dystrophy.
单亲二体（UPD）是一种罕见的染色体异常。我们对早发性视网膜营养不良病例进行了全外显子组测序（WES），并鉴定出两例可能由UPD引起的病例。在此，我们报告这两例病例，并试图阐明由UPD引起的视网膜营养不良的临床情况。
对两名患者及其非近亲的父母进行了WES分析。对疑似先天性糖基化障碍（CDG）的病例进行了功能分析。我们获取了临床病例数据并查阅了文献。
在病例1中，检测到 中一个新的纯合c.57G>C，p.（Trp19Cys）变异。遗传分析提示4号染色体存在母源性UPD，功能分析证实为CDG。临床发现显示早发性视网膜营养不良、智力残疾和癫痫。在病例2中，检测到 中一个纯合的Alu插入（c.4052_4053ins328，p.[Tyr1352Alafs]）。怀疑8号染色体存在母源性UPD。临床表现与 相关的视网膜色素变性一致。虽然由UPD引起的视网膜营养不良的临床特征可能有所不同，但大多数病例在儿童期发病。
关于UPD引起的视网膜营养不良的报道有限，表明其较为罕见。对于小儿视网膜营养不良病例，可能需要进行遗传咨询。
