PDF(Pubmed)
Abstract：
OBJECTIVE: To investigate the genetic and clinical characteristics of patients with a large heterozygous copy number deletion on 7q31.31-7q31.32.
METHODS: A family with familial exudative vitreoretinopathy (FEVR) phenotype was included in the study. Whole-exome sequencing (WES) was initially used to locate copy number variations (CNVs) on 7q31.31-31.32, but failed to detect the precise breakpoint. The long-read sequencing, Oxford Nanopore sequencing Technology (ONT) was used to get the accurate breakpoint which is verified by quantitative real-time polymerase chain reaction (QPCR) and Sanger Sequencing.
RESULTS: The proband, along with her father and younger brother, were found to have a heterozygous 4.5 Mb CNV deletion located on 7q31.31-31.32, which included the FEVR-related gene TSPAN12. The specific deletion was confirmed as del(7)(q31.31q31.32)chr7:g.119451239_123956818del. The proband exhibited a phase 2A FEVR phenotype, characterized by a falciform retinal fold, macular dragging, and peripheral neovascularization with leaking of fluorescence. These symptoms led to a significant decrease in visual acuity in both eyes. On the other hand, the affected father and younger brother showed a milder phenotype.
CONCLUSIONS: The heterozygous CNV deletion located on 7q31.31-7q31.32 is associated with the FEVR phenotype. The use of long-read sequencing techniques is essential for accurate molecular diagnosis of genetic disorders.
METHODS: A family with familial exudative vitreoretinopathy (FEVR) phenotype was included in the study. Whole-exome sequencing (WES) was initially used to locate copy number variations (CNVs) on 7q31.31-31.32, but failed to detect the precise breakpoint. The long-read sequencing, Oxford Nanopore sequencing Technology (ONT) was used to get the accurate breakpoint which is verified by quantitative real-time polymerase chain reaction (QPCR) and Sanger Sequencing.
RESULTS: The proband, along with her father and younger brother, were found to have a heterozygous 4.5 Mb CNV deletion located on 7q31.31-31.32, which included the FEVR-related gene TSPAN12. The specific deletion was confirmed as del(7)(q31.31q31.32)chr7:g.119451239_123956818del. The proband exhibited a phase 2A FEVR phenotype, characterized by a falciform retinal fold, macular dragging, and peripheral neovascularization with leaking of fluorescence. These symptoms led to a significant decrease in visual acuity in both eyes. On the other hand, the affected father and younger brother showed a milder phenotype.
CONCLUSIONS: The heterozygous CNV deletion located on 7q31.31-7q31.32 is associated with the FEVR phenotype. The use of long-read sequencing techniques is essential for accurate molecular diagnosis of genetic disorders.
摘要：
目的：研究7q31.31-7q31.32上大量杂合拷贝数缺失患者的遗传和临床特征。
方法：本研究包括一个家族性渗出性玻璃体视网膜病变（FEVR）表型的家族。全外显子组测序（WES）最初用于定位7q31.31-31.32上的拷贝数变异（CNV），但未能检测到精确的断点。长读数测序，采用牛津纳米孔测序技术（ONT）获得准确的断点，并通过定量实时聚合酶链反应（QPCR）和Sanger测序进行验证。
结果：先证者，还有她的父亲和弟弟,发现在7q31.31-31.32上存在一个杂合的4.5MbCNV缺失，其中包括FEVR相关基因TSPAN12。特异性缺失被确认为del(7)(q31.31q31.32)chr7:g.119451239_123956818del。先证者表现出2A阶段FEVR表型，以镰状视网膜褶皱为特征，黄斑拖动，和荧光泄漏的外周新生血管形成。这些症状导致双眼视敏度显著降低。另一方面,受影响的父亲和弟弟表现出温和的表型。
结论：位于7q31.31-7q31.32上的杂合CNV缺失与FEVR表型相关。长读数测序技术的使用对于遗传疾病的准确分子诊断至关重要。
方法：本研究包括一个家族性渗出性玻璃体视网膜病变（FEVR）表型的家族。全外显子组测序（WES）最初用于定位7q31.31-31.32上的拷贝数变异（CNV），但未能检测到精确的断点。长读数测序，采用牛津纳米孔测序技术（ONT）获得准确的断点，并通过定量实时聚合酶链反应（QPCR）和Sanger测序进行验证。
结果：先证者，还有她的父亲和弟弟,发现在7q31.31-31.32上存在一个杂合的4.5MbCNV缺失，其中包括FEVR相关基因TSPAN12。特异性缺失被确认为del(7)(q31.31q31.32)chr7:g.119451239_123956818del。先证者表现出2A阶段FEVR表型，以镰状视网膜褶皱为特征，黄斑拖动，和荧光泄漏的外周新生血管形成。这些症状导致双眼视敏度显著降低。另一方面,受影响的父亲和弟弟表现出温和的表型。
结论：位于7q31.31-7q31.32上的杂合CNV缺失与FEVR表型相关。长读数测序技术的使用对于遗传疾病的准确分子诊断至关重要。
