Clinical and Molecular Characterization ofPROM1-Related Retinal Degeneration

错义突变 移码突变 畏光 遗传学 视网膜变性 色素性视网膜炎 生物 视网膜 表型 医学 眼科 基因
作者
Jasmina Cehajic‐Kapetanovic,Johannes Birtel,Michelle E. McClements,Morag Shanks,Penny Clouston,Susan M. Downes,Peter Charbel Issa,Robert E. MacLaren
出处
期刊:JAMA network open [American Medical Association]
卷期号:2 (6): e195752-e195752 被引量:61
标识
DOI:10.1001/jamanetworkopen.2019.5752
摘要

Importance

ThePROM1gene,commonly associated with cone-rod dystrophies, may have dominant or recessive phenotypes that influence disease onset and severity.

Objective

To characterize the clinical phenotype and molecular genetic variations in patients withPROM1variants.

Design, Setting, and Participants

This case-series study was conducted at 2 specialist retinal genetics clinics and examined 19 consecutively enrolled patients withPROM1-related retinal degeneration. Data were collected and analyzed from May 2018 to December 2018.

Main Outcomes and Measures

Results of ophthalmic examination, retinal imaging, and molecular genetic analysis by next-generation sequencing.

Results

Of 19 patients, 13 (68%) were women, and age ranged from 11 to 70 years. All patients presented with central visual loss, with or without photophobia. Individuals with recessive variants commonly had severe loss of visual acuity by their 20s, whereas the dominant variant was associated with a milder phenotype, with most patients retaining good vision into late adulthood. The recessive cases were associated with a panretinal dystrophy of cone-rod phenotype with early macular involvement, whereas the dominant variants were associated with a cone-rod phenotype that was restricted to the macula with predominantly cone dysfunction. Next-generation sequencing identified 3 novel and 9 previously reported variants inPROM1. Recessive mutations included 6 truncating variants (3 nonsense and 3 frameshift), 4 splice site variants, and 1 missense variant. All 6 dominant variants were associated with a c.1117C>T missense variant. The variants were distributed throughout thePROM1genomic sequence with no specific clustering on protein domains.

Conclusions and Relevance

In this case-series study,PROM1recessive variants were associated with early-onset, severe panretinal degeneration. The similar phenotypes observed in patients with homozygous missense variants and splice site variants compared with similarly aged patients with truncating variants suggests that all recessive variants have a null (or loss of function close to null) outcome onPROM1function. In contrast, the dominant missense cases were associated with a milder, cone-driven phenotype, suggesting that the dominant disease is preferentially associated with cones. This has implications for the development of treatments for this severely blinding disease, and adeno-associated viral vector–based gene therapy and optogenetics could become successful treatment options.
最长约 10秒,即可获得该文献文件

科研通智能强力驱动
Strongly Powered by AbleSci AI
科研通是完全免费的文献互助平台,具备全网最快的应助速度,最高的求助完成率。 对每一个文献求助,科研通都将尽心尽力,给求助人一个满意的交代。
实时播报
huihui发布了新的文献求助10
刚刚
刚刚
大方大船完成签到,获得积分10
4秒前
Author发布了新的文献求助10
5秒前
科研通AI6.3应助qscheng采纳,获得10
5秒前
ZIYE发布了新的文献求助10
6秒前
田様应助11采纳,获得10
6秒前
风声3492881045应助呆萌海蓝采纳,获得20
6秒前
赘婿应助sinkkkkkk采纳,获得10
6秒前
9秒前
9秒前
LL完成签到 ,获得积分10
10秒前
王帅崽完成签到 ,获得积分10
10秒前
fei完成签到,获得积分10
10秒前
火星上唇膏完成签到 ,获得积分10
11秒前
Hello应助ZIYE采纳,获得10
13秒前
zz发布了新的文献求助10
14秒前
Knight发布了新的文献求助10
15秒前
15秒前
七海海发布了新的文献求助10
15秒前
小二郎应助科研小贩采纳,获得10
16秒前
16秒前
思源应助余欢阙忧采纳,获得10
16秒前
17秒前
17秒前
Lucas应助威力先生采纳,获得10
18秒前
18秒前
Orange应助何大爷采纳,获得10
18秒前
18秒前
坦率的芹菜完成签到,获得积分20
19秒前
19秒前
21秒前
21秒前
共勉完成签到,获得积分10
21秒前
溯su发布了新的文献求助10
21秒前
21秒前
欢喜涫完成签到,获得积分10
21秒前
惠香香的发布了新的文献求助10
21秒前
Hesper完成签到 ,获得积分10
22秒前
Di完成签到,获得积分10
22秒前
高分求助中
Malcolm Fraser : a biography 700
Signals, Systems, and Signal Processing 610
天津市智库成果选编 600
Climate change and sports: Statistics report on climate change and sports 500
Forced degradation and stability indicating LC method for Letrozole: A stress testing guide 500
Organic Reactions Volume 118 400
A Foreign Missionary on the Long March: The Unpublished Memoirs of Arnolis Hayman of the China Inland Mission 400
热门求助领域 (近24小时)
化学 材料科学 医学 生物 纳米技术 工程类 有机化学 化学工程 生物化学 计算机科学 物理 内科学 复合材料 催化作用 物理化学 光电子学 电极 细胞生物学 基因 无机化学
热门帖子
关注 科研通微信公众号,转发送积分 6465916
求助须知:如何正确求助?哪些是违规求助? 8272668
关于积分的说明 17638814
捐赠科研通 5540317
什么是DOI,文献DOI怎么找? 2907772
邀请新用户注册赠送积分活动 1884803
关于科研通互助平台的介绍 1732535