Abstract：
To explore the clinical manifestations and search for the variants of six related genes (LRP5, FZD4, TSPAN12, NDP, KIF11 and ZNF408) in Chinese patients with familial exudative vitreoretinopathy (FEVR), and investigate the correlation between the genetic variants and the clinical characteristics.
Clinical data, including the retinal artery angle, acquired from wide-field fundus imaging, structural and microvascular features of the retina obtained from optical coherence tomography (OCT) and OCT angiography (OCTA) were collected from 33 pedigrees. Furthermore, mutation screening was performed. Variants filtering, bioinformatics analysis and Sanger sequencing were conducted to verify the variants.
Twenty-one variants were successfully detected in 16 of 33 families, of which 10 variants were newly identified. The proportion of variants in LRP5, FZD4, TSPAN12, NDP and KIF11 was 38.1% (8/21), 33.3% (7/21), 19.1% (4/21), 4.8% (1/21) and 4.8% (1/21), respectively. Three new variants were considered to be pathogenic or likely pathogenic. The FEVR group tended to exhibit a smaller retinal artery angle, higher incidence of foveal hypoplasia and lower vascular density compared to the control group. Patients who harboured variants of FZD4 exhibited greater severity of FEVR than those with LRP5 variants. However, those who harboured LRP5 variants tended to possess lower foveal vascular density.
Six known pathogenic genes were screened in 33 pedigrees with FEVR in our study, which revealed 10 novel variants. These findings enrich the clinical features and mutation spectrum in Chinese patients with FEVR, revealing the genotype-phenotype relationship, and contributing to the diagnosis and treatment of the disease.Key messagesWe identified 21 variants in 5 genes (LRP5, FZD4, TSPAN12, NDP and KIF11) associated with FEVR, 10 of which are novel (three were pathogenic or likely pathogenic).The proportion of variants was the highest for the LRP5 gene.FZD4 variants may be responsible for greater FEVR severity than LRP5 variants.
Clinical data, including the retinal artery angle, acquired from wide-field fundus imaging, structural and microvascular features of the retina obtained from optical coherence tomography (OCT) and OCT angiography (OCTA) were collected from 33 pedigrees. Furthermore, mutation screening was performed. Variants filtering, bioinformatics analysis and Sanger sequencing were conducted to verify the variants.
Twenty-one variants were successfully detected in 16 of 33 families, of which 10 variants were newly identified. The proportion of variants in LRP5, FZD4, TSPAN12, NDP and KIF11 was 38.1% (8/21), 33.3% (7/21), 19.1% (4/21), 4.8% (1/21) and 4.8% (1/21), respectively. Three new variants were considered to be pathogenic or likely pathogenic. The FEVR group tended to exhibit a smaller retinal artery angle, higher incidence of foveal hypoplasia and lower vascular density compared to the control group. Patients who harboured variants of FZD4 exhibited greater severity of FEVR than those with LRP5 variants. However, those who harboured LRP5 variants tended to possess lower foveal vascular density.
Six known pathogenic genes were screened in 33 pedigrees with FEVR in our study, which revealed 10 novel variants. These findings enrich the clinical features and mutation spectrum in Chinese patients with FEVR, revealing the genotype-phenotype relationship, and contributing to the diagnosis and treatment of the disease.Key messagesWe identified 21 variants in 5 genes (LRP5, FZD4, TSPAN12, NDP and KIF11) associated with FEVR, 10 of which are novel (three were pathogenic or likely pathogenic).The proportion of variants was the highest for the LRP5 gene.FZD4 variants may be responsible for greater FEVR severity than LRP5 variants.
摘要：
探索临床表现并寻找六个相关基因（LRP5，FZD4，TSPAN12，NDP，KIF11和ZNF408）在中国家族性渗出性玻璃体视网膜病变（FEVR）患者中，并探讨遗传变异与临床特征的相关性。
临床数据，包括视网膜动脉角度,从宽视野眼底成像获得，从33个家系收集了光学相干断层扫描(OCT)和OCT血管造影(OCTA)获得的视网膜结构和微血管特征.此外，进行突变筛选。变体过滤，进行生物信息学分析和Sanger测序以验证变异。
在33个家族中的16个中成功检测到21个变异，其中10个变体是新鉴定的。LRP5、FZD4、TSPAN12、NDP和KIF11中变异体的比例为38.1%(8/21),33.3%（7/21），19.1%（4/21），4.8%(1/21)和4.8%(1/21)，分别。三个新的变异体被认为是致病的或可能致病的。FEVR组倾向于表现出更小的视网膜动脉角度，与对照组相比，中央凹发育不全的发生率更高，血管密度更低。携带FZD4变体的患者表现出比具有LRP5变体的患者更严重的FEVR。然而,那些拥有LRP5变异体的人倾向于拥有较低的中央凹血管密度。
在我们的研究中，在33个FEVR家系中筛选了六个已知的致病基因，揭示了10种新颖的变体。这些发现丰富了中国FEVR患者的临床特征和突变谱,揭示基因型-表型关系，并有助于疾病的诊断和治疗。关键信息我们确定了与FEVR相关的5个基因（LRP5，FZD4，TSPAN12，NDP和KIF11）中的21个变体，其中10个是新的(三个是致病性的或可能致病性的)。LRP5基因的变异比例最高。FZD4变体可负责比LRP5变体更高的FEVR严重性。
临床数据，包括视网膜动脉角度,从宽视野眼底成像获得，从33个家系收集了光学相干断层扫描(OCT)和OCT血管造影(OCTA)获得的视网膜结构和微血管特征.此外，进行突变筛选。变体过滤，进行生物信息学分析和Sanger测序以验证变异。
在33个家族中的16个中成功检测到21个变异，其中10个变体是新鉴定的。LRP5、FZD4、TSPAN12、NDP和KIF11中变异体的比例为38.1%(8/21),33.3%（7/21），19.1%（4/21），4.8%(1/21)和4.8%(1/21)，分别。三个新的变异体被认为是致病的或可能致病的。FEVR组倾向于表现出更小的视网膜动脉角度，与对照组相比，中央凹发育不全的发生率更高，血管密度更低。携带FZD4变体的患者表现出比具有LRP5变体的患者更严重的FEVR。然而,那些拥有LRP5变异体的人倾向于拥有较低的中央凹血管密度。
在我们的研究中，在33个FEVR家系中筛选了六个已知的致病基因，揭示了10种新颖的变体。这些发现丰富了中国FEVR患者的临床特征和突变谱,揭示基因型-表型关系，并有助于疾病的诊断和治疗。关键信息我们确定了与FEVR相关的5个基因（LRP5，FZD4，TSPAN12，NDP和KIF11）中的21个变体，其中10个是新的(三个是致病性的或可能致病性的)。LRP5基因的变异比例最高。FZD4变体可负责比LRP5变体更高的FEVR严重性。
