Khan Arif O, Aldahmesh Mohammed A, Abu-Safieh Leen, Alkuraya Fowzan S
Division of Pediatric Ophthalmology, King Khaled Eye Specialist Hospital , Riyadh , Saudi Arabia .
Ophthalmic Genet. 2014 Sep;35(3):130-7. doi: 10.3109/13816810.2013.804097. Epub 2013 Jun 14.
To describe three siblings with childhood cone-rod dystrophy and macular cystic degeneration in a family with apparently variable phenotypes of CRB1-related recessive retinal dystrophy.
Ophthalmologic examination (including electroretinography (ERG), ocular coherence tomography (OCT), and intravenous fluorescein angiography when possible) and homozygosity analysis guided candidate gene testing.
When the proband was evaluated at 7 years old for progressive visual loss, fundus exam was unremarkable (including no macular thickening clinically or by OCT) but ERG revealed cone-rod dysfunction with an electronegative waveform. Four years later repeat examination was significant for bilateral macular cystic degeneration and immediate family members were evaluated. Both the older sister (15 years old) and the younger brother (7 years old) had cone-rod dystrophy with macular cystic degeneration. Both the father (45 years old) and mother (35 years old) had had early adult-onset nyctalopia with later eventual loss of central vision; examination revealed dystrophic retinas with mostly peripheral clumped and/or nummular pigment and macular atrophy. ERG for both the older sister and younger brother confirmed cone-rod dysfunction (without an electronegative waveform) and was non-recordable for both the parents. Homozygosity analysis guided candidate gene analysis and confirmatory Sanger sequencing for the family uncovered a homozygous CRB1 mutation (c.80G > T [p.Cys27Phe]) in affected family members.
The phenotypic spectrum of recessive CRB1 mutation includes childhood cone-rod dystrophy with macular cystic degeneration and the associated ERG can be electronegative.
描述一个患有CRB1相关隐性视网膜营养不良明显可变表型的家庭中，三名患有儿童期视锥-视杆营养不良和黄斑囊性变性的兄弟姐妹。
眼科检查（包括视网膜电图（ERG）、光学相干断层扫描（OCT），并在可能时进行静脉荧光素血管造影）和纯合性分析指导候选基因检测。
先证者7岁时因进行性视力丧失接受评估，眼底检查无明显异常（包括临床或OCT检查均未发现黄斑增厚），但ERG显示视锥-视杆功能障碍且波形为阴性。四年后复查发现双侧黄斑囊性变性，并对直系亲属进行了评估。姐姐（15岁）和弟弟（7岁）均患有视锥-视杆营养不良伴黄斑囊性变性。父亲（45岁）和母亲（35岁）均有成年早期发作的夜盲症，后期最终丧失中心视力；检查发现视网膜营养不良，主要表现为周边聚集和/或钱币状色素沉着以及黄斑萎缩。姐姐和弟弟的ERG均证实存在视锥-视杆功能障碍（无阴性波形），父母的ERG均无法记录。纯合性分析指导候选基因分析，对该家庭进行的验证性桑格测序发现，患病家庭成员中存在纯合的CRB1突变（c.80G＞T [p.Cys27Phe]）。
隐性CRB1突变的表型谱包括儿童期视锥-视杆营养不良伴黄斑囊性变性，且相关的ERG可能为阴性。
