University College London Institute of Ophthalmology, London, England2Vitreoretinal Department, Moorfields Eye Hospital, London, England3Professorial Unit, Moorfields Eye Hospital, London, England.
University College London Institute of Ophthalmology, London, England.
JAMA Ophthalmol. 2014 Aug;132(8):996-1001. doi: 10.1001/jamaophthalmol.2014.940.
We describe novel ocular phenotypic features caused by mutations in ADAMTS18. The exact role of ADAMTS18 in ocular disease is unclear, and our work further contributes to the understanding of this gene and its protein.
To expand the phenotypic characterization in patients with homozygous mutations in ADAMTS18 and report novel mutational data.
DESIGN, SETTING, AND PARTICIPANTS: A case series with genetic investigations was conducted at tertiary referral clinical and university settings. Three families participated.
Phenotype and genotype description of 3 families.
Four affected patients from 3 families with an unusual ocular phenotype had full ophthalmic and systemic examination. A single affected individual in the first family had bilateral microcornea, ectopic pupils, and cone-rod dystrophy. In a second family, 2 brothers showed bilateral microcornea, childhood cataract, ectopia lentis, rhegmatogenous retinal detachment, and cone-rod dystrophy. In the third family, a single affected individual had the same features as those in family 2, without ectopia lentis. Causative mutations were sought using homozygosity mapping, Sanger sequencing, and massively parallel sequencing of the whole exome. Novel homozygous mutations in ADAMTS18 were identified, consisting of c.1067T>A [p.L356*] in the first proband, c.2159G>C [p.C720S] in the 2 affected brothers, and c.1952G>A [p.R651Q] in the third proband. All 3 mutations are predicted to be pathogenic.
Mutations in ADAMTS18 are associated with ocular developmental abnormalities including microcornea, ectopia lentis, and early onset of cone-rod dystrophy. This report provides further evidence that ADAMTS18 plays a key role in ocular development. Physicians should consider screening ADAMTS18 in patients with microcornea and cone-rod dystrophy.
我们描述了由 ADAMTS18 基因突变引起的新型眼部表型特征。ADAMTS18 在眼部疾病中的确切作用尚不清楚，我们的工作进一步加深了对该基因及其蛋白的理解。
扩大 ADAMTS18 纯合突变患者的表型特征描述，并报告新的突变数据。
设计、地点和参与者：在三级转诊临床和大学环境中进行了一项遗传研究的病例系列研究。有 3 个家庭参与。
3 个家庭的表型和基因型描述。
来自 3 个家庭的 4 名受影响患者表现出不寻常的眼部表型，进行了全面的眼科和全身检查。第一个家庭的 1 名受影响个体有双侧小角膜、瞳孔异位和圆锥-杆状营养不良。第二个家庭的 2 个兄弟表现为双侧小角膜、儿童期白内障、晶状体异位、孔源性视网膜脱离和圆锥-杆状营养不良。第三个家庭的 1 名受影响个体表现出与家庭 2 相同的特征，无晶状体异位。使用纯合子作图、Sanger 测序和外显子组全序列平行测序寻找致病突变。鉴定出 ADAMTS18 的新型纯合突变，包括第一个先证者的 c.1067T>A [p.L356*]、2 个受影响兄弟的 c.2159G>C [p.C720S]和第三个先证者的 c.1952G>A [p.R651Q]。所有 3 个突变均被预测为致病性的。
ADAMTS18 突变与眼部发育异常有关，包括小角膜、晶状体异位和圆锥-杆状营养不良的早期发病。本报告进一步证实 ADAMTS18 在眼部发育中起关键作用。医生应考虑在小角膜和圆锥-杆状营养不良患者中筛查 ADAMTS18。
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