次世代シークエンシングに基づいたコロイダー血症の臨床診断と包括的な突然変異解析、臨床解析を行った

Next-generation sequencing-based clinical diagnosis of choroideremia and comprehensive mutational and clinical analyses.

• Feng-Juan Gao
• Guo-Hong Tian
• Fang-Yuan Hu
• Dan-Dan Wang
• Jian-Kang Li
• Qing Chang
• Fang Chen
• Ge-Zhi Xu
• Wei Liu
• Ji-Hong Wu

抄録

背景:

中国人コロイダミア患者7名の臨床所見と遺伝学的所見を報告する。

BACKGROUND: To report the clinical and genetic findings from seven Chinese patients with choroideremia.

方法:

網膜色素変性症（RP）が臨床的に疑われる患者 578 人が包括的な眼科検査を受けた。全患者の検体について次世代シークエンシング（NGS）を実施した。本研究で特定された絨毛網膜色素変性症患者の詳細な臨床的特徴は、マルチモーダルイメージングを用いて評価されました。

METHODS: Five hundred seventy-eight patients with a clinically suspected diagnosis of retinitis pigmentosa (RP) underwent comprehensive ophthalmic examinations. Next-generation sequencing (NGS) was performed on samples from all patients. Detailed clinical characteristics of the patients with choroideremia identified in this study were assessed using multimodal imaging.

結果:

7人のコロイダーミア患者が同定され、CHMにおける6つの新規変異（c.1960T>C p.Ter654Gln、c.1257del p.Ile420*fs1、c.1103_1121delATGGCAACACTCCATTTTT p.Tyr368Cysfs35、c.1414-2A>T、およびc.1213C>T p.Gln405Ter、c.117-1G>A）が明らかにされました。すべての変異は欠失性変異であり、2つはフレームシフト、2つはナンセンス変異、2つはスプライシング変異、1つはリードスルー変異であった。これらの患者の臨床表現型は著しく異質であり、夜盲症、視野狭窄、徐々に視力が低下するなど、RPと共通する臨床的特徴を多く有していた。しかし，コロイデミア患者では，色素肥大や凝集，脈絡網膜萎縮が認められ，大多数のコロイデミア患者では網膜外層に網膜尿細管を呈していた．

RESULTS: Seven patients with choroideremia were identified, and six novel variants in CHM (c.1960 T > C p.Ter654Gln, c.1257del p.Ile420*fs1, c.1103_1121delATGGCAACACTCCATTTTT p.Tyr368Cysfs35, c.1414-2A > T, and c.1213C > T p.Gln405Ter, c.117-1G > A) were revealed. All variants were deleterious mutations: two were frameshifts, two were nonsense mutations, two were splicing mutations, and one was a readthrough mutation. The clinical phenotypes of these patients were markedly heterogeneous, and they shared many common clinical features with RP, including night blindness, constriction of the visual field and gradually reduced visual acuity. However, patients with choroideremia showed pigment hypertrophy and clumping, and chorioretinal atrophy, and a majority of patients with choroideremia presented with retinal tubulations in the outer layer of the retina.

結論:

本研究では、NGSを用いて正確に診断された7名のコロイデミア患者の遺伝子型と表現型の詳細な説明を行った。これらの知見は、コロイダー血症の遺伝学と表現型についてのより良い理解を提供します。

CONCLUSIONS: We provide a detailed description of the genotypes and phenotypes of seven patients with choroideremia who were accurately diagnosed using NGS. These findings provide a better understanding of the genetics and phenotypes of choroideremia.