Abstract：
UNASSIGNED: To explore patterns of disease expression in Alagille syndrome (ALGS).
UNASSIGNED: Patients underwent ophthalmic examination, optical coherence tomography (OCT) imaging, fundus intravenous fluorescein angiography (IVFA), perimetry and full-field electroretinograms (ffERGs). An adult ALGS patient had multimodal imaging and specialized perimetry.
UNASSIGNED: The proband (P1) had a heterozygous pathogenic variant in JAG1; (p.Gln410Ter) and was incidentally diagnosed at age 7 with a superficial retinal hemorrhage, vascular tortuosity, and midperipheral pigmentary changes. The hemorrhage recurred 15 months later. Her monozygotic twin sister (P2) had a retinal hemorrhage at the same location at age 11. Visual acuities for both patients were 20/30 in each eye. IVFA was normal. OCT showed thinning of the outer nuclear in the peripapillary retina. A ffERG showed normal cone-mediated responses in P1 (rod-mediated ERGs not documented), normal ffERGs in P2. Coagulation and liver function were normal. An unrelated 42-year-old woman with a de-novo pathogenic variant (p. Gly386Arg) in JAG1 showed a similar pigmentary retinopathy and hepatic vascular anomalies; rod and cone function was normal across large expanses of structurally normal retina that sharply transitioned to a blind atrophic peripheral retina.
UNASSIGNED: Nearly identical recurrent intraretinal hemorrhages in monozygotic twins with ALGS suggest a shared subclinical microvascular abnormality. We hypothesize that the presence of large areas of functionally and structurally intact retina surrounded by severe chorioretinal degeneration, is against a predominant involvement of JAG1 in the function of the neurosensory retina, and that instead, primary abnormalities of chorioretinal vascular development and/or homeostasis may drive the peculiar phenotypes.
UNASSIGNED: Patients underwent ophthalmic examination, optical coherence tomography (OCT) imaging, fundus intravenous fluorescein angiography (IVFA), perimetry and full-field electroretinograms (ffERGs). An adult ALGS patient had multimodal imaging and specialized perimetry.
UNASSIGNED: The proband (P1) had a heterozygous pathogenic variant in JAG1; (p.Gln410Ter) and was incidentally diagnosed at age 7 with a superficial retinal hemorrhage, vascular tortuosity, and midperipheral pigmentary changes. The hemorrhage recurred 15 months later. Her monozygotic twin sister (P2) had a retinal hemorrhage at the same location at age 11. Visual acuities for both patients were 20/30 in each eye. IVFA was normal. OCT showed thinning of the outer nuclear in the peripapillary retina. A ffERG showed normal cone-mediated responses in P1 (rod-mediated ERGs not documented), normal ffERGs in P2. Coagulation and liver function were normal. An unrelated 42-year-old woman with a de-novo pathogenic variant (p. Gly386Arg) in JAG1 showed a similar pigmentary retinopathy and hepatic vascular anomalies; rod and cone function was normal across large expanses of structurally normal retina that sharply transitioned to a blind atrophic peripheral retina.
UNASSIGNED: Nearly identical recurrent intraretinal hemorrhages in monozygotic twins with ALGS suggest a shared subclinical microvascular abnormality. We hypothesize that the presence of large areas of functionally and structurally intact retina surrounded by severe chorioretinal degeneration, is against a predominant involvement of JAG1 in the function of the neurosensory retina, and that instead, primary abnormalities of chorioretinal vascular development and/or homeostasis may drive the peculiar phenotypes.
摘要：
■探索Alagille综合征（ALGS）的疾病表达模式。
■患者接受眼科检查，光学相干断层扫描（OCT）成像，眼底静脉荧光素血管造影（IVFA），视野和全场视网膜电图（ffERGs）。一名成年ALGS患者进行了多模态成像和专门的视野检查。
■先证者（P1）在JAG1中具有杂合致病性变异；（p。Gln410Ter），并在7岁时被偶然诊断为浅表视网膜出血，血管弯曲,和中期外周色素变化。15个月后出血复发。她的同卵双胞胎姐妹（P2）在11岁时在同一位置发生了视网膜出血。两名患者的每只眼睛的视力为20/30。IVFA正常。OCT显示乳头状视网膜外核变薄。一个ffERG在P1中显示正常的视锥介导的反应（杆状介导的ERG未记录），P2中的正常ffERGs。凝血和肝功能正常。一名无关的42岁女性，具有从头致病变异（第Gly386Arg）在JAG1中显示出类似的色素性视网膜病变和肝血管异常；在结构正常的视网膜的大片区域中，视杆和视锥功能正常，急剧过渡到盲目的萎缩性周围视网膜。
■在单卵双生子合并ALGS中，几乎相同的复发性视网膜内出血提示共有亚临床微血管异常。我们假设存在大面积的功能和结构完整的视网膜被严重的脉络膜视网膜变性包围，反对JAG1主要参与神经感觉视网膜的功能，相反，脉络膜视网膜血管发育和/或体内平衡的原发性异常可能导致特殊的表型。
■患者接受眼科检查，光学相干断层扫描（OCT）成像，眼底静脉荧光素血管造影（IVFA），视野和全场视网膜电图（ffERGs）。一名成年ALGS患者进行了多模态成像和专门的视野检查。
■先证者（P1）在JAG1中具有杂合致病性变异；（p。Gln410Ter），并在7岁时被偶然诊断为浅表视网膜出血，血管弯曲,和中期外周色素变化。15个月后出血复发。她的同卵双胞胎姐妹（P2）在11岁时在同一位置发生了视网膜出血。两名患者的每只眼睛的视力为20/30。IVFA正常。OCT显示乳头状视网膜外核变薄。一个ffERG在P1中显示正常的视锥介导的反应（杆状介导的ERG未记录），P2中的正常ffERGs。凝血和肝功能正常。一名无关的42岁女性，具有从头致病变异（第Gly386Arg）在JAG1中显示出类似的色素性视网膜病变和肝血管异常；在结构正常的视网膜的大片区域中，视杆和视锥功能正常，急剧过渡到盲目的萎缩性周围视网膜。
■在单卵双生子合并ALGS中，几乎相同的复发性视网膜内出血提示共有亚临床微血管异常。我们假设存在大面积的功能和结构完整的视网膜被严重的脉络膜视网膜变性包围，反对JAG1主要参与神经感觉视网膜的功能，相反，脉络膜视网膜血管发育和/或体内平衡的原发性异常可能导致特殊的表型。
