Abstract：
Pierson syndrome and X-linked Alport syndrome result from pathogenic variants in LAMB2 and COL4A5, respectively, and both affect basement membranes in the kidney and the eye. This study describes the ocular features in an individual with a homozygous LAMB2 pathogenic variant and compares the reported abnormalities in Pierson syndrome with those in Alport syndrome.
A 28-year-old man who developed kidney failure 10 years previously and subsequently had an atrial septal defect repair was suspected of having genetic kidney disease on the basis of his likely diagnosis of Focal and Segmental Glomerulosclerosis (FSGS), his young age at presentation, and his cardiac anomaly. He then underwent Whole Exome Sequencing and a formal ophthalmological examination.
The patient was found to have a homozygous Likely Pathogenic missense variant (p.(Arg1719Cys)) in LAMB2 consistent with the diagnosis of Pierson syndrome. He had normal visual acuity, normal optic globe and cornea size, and normal lens appearance on direct examination. Upon further testing, his cornea demonstrated central thinning. There was also increased corneal endothelial pleomorphism, a reduced foveal reflex, and a blunted foveal curvature, similar to the features seen in X-linked Alport syndrome.
Our patient had a later onset form of Pierson syndrome or \"FSGS type 5, with or without ocular abnormalities,\" consistent with his \"milder\" LAMB2 missense variant. The resemblance of the ocular features in Pierson syndrome and X-linked Alport syndrome suggests that mutations in LAMB2 and COL4A5 have similar effects on basement membranes and the pathogenesis of ocular damage.
A 28-year-old man who developed kidney failure 10 years previously and subsequently had an atrial septal defect repair was suspected of having genetic kidney disease on the basis of his likely diagnosis of Focal and Segmental Glomerulosclerosis (FSGS), his young age at presentation, and his cardiac anomaly. He then underwent Whole Exome Sequencing and a formal ophthalmological examination.
The patient was found to have a homozygous Likely Pathogenic missense variant (p.(Arg1719Cys)) in LAMB2 consistent with the diagnosis of Pierson syndrome. He had normal visual acuity, normal optic globe and cornea size, and normal lens appearance on direct examination. Upon further testing, his cornea demonstrated central thinning. There was also increased corneal endothelial pleomorphism, a reduced foveal reflex, and a blunted foveal curvature, similar to the features seen in X-linked Alport syndrome.
Our patient had a later onset form of Pierson syndrome or \"FSGS type 5, with or without ocular abnormalities,\" consistent with his \"milder\" LAMB2 missense variant. The resemblance of the ocular features in Pierson syndrome and X-linked Alport syndrome suggests that mutations in LAMB2 and COL4A5 have similar effects on basement membranes and the pathogenesis of ocular damage.
摘要：
■Pierson综合征和X连锁Alport综合征分别由LAMB2和COL4A5的致病变异引起，都会影响肾脏和眼睛的基底膜。这项研究描述了具有纯合LAMB2致病性变异体的个体的眼部特征，并比较了Pierson综合征与Alport综合征中报告的异常。
一名28岁男子10年前出现肾衰竭，随后进行了房间隔缺损修复，根据他可能诊断为局灶性和节段性肾小球硬化（FSGS），他被怀疑患有遗传性肾病，他年轻的时候在演讲中，还有他的心脏异常.然后，他接受了整个外显子组测序和正式的眼科检查。
■发现患者具有纯合的可能致病错义变体（p。（Arg1719Cys））在LAMB2中与Pierson综合征的诊断相符。他的视力正常,正常视神经球和角膜大小，和正常的晶状体外观直接检查。经过进一步测试,他的角膜显示中央变薄。角膜内皮多态性也增加，减少的中央凹反射，和钝化的中央凹弯曲，与X连锁Alport综合征的特征相似。
■我们的患者患有Pierson综合征或FSGS5型，有或没有眼部异常，\"与他的\"温和\"LAMB2错觉变体一致。Pierson综合征和X连锁Alport综合征的眼部特征相似，表明LAMB2和COL4A5的突变对基底膜和眼部损伤的发病机理具有相似的作用。
一名28岁男子10年前出现肾衰竭，随后进行了房间隔缺损修复，根据他可能诊断为局灶性和节段性肾小球硬化（FSGS），他被怀疑患有遗传性肾病，他年轻的时候在演讲中，还有他的心脏异常.然后，他接受了整个外显子组测序和正式的眼科检查。
■发现患者具有纯合的可能致病错义变体（p。（Arg1719Cys））在LAMB2中与Pierson综合征的诊断相符。他的视力正常,正常视神经球和角膜大小，和正常的晶状体外观直接检查。经过进一步测试,他的角膜显示中央变薄。角膜内皮多态性也增加，减少的中央凹反射，和钝化的中央凹弯曲，与X连锁Alport综合征的特征相似。
■我们的患者患有Pierson综合征或FSGS5型，有或没有眼部异常，\"与他的\"温和\"LAMB2错觉变体一致。Pierson综合征和X连锁Alport综合征的眼部特征相似，表明LAMB2和COL4A5的突变对基底膜和眼部损伤的发病机理具有相似的作用。
