PDF(Pubmed)
Abstract：
Infantile nystagmus syndrome (INS), or congenital nystagmus (CN), refers to a group of ocular motor disorders characterized by rapid to-and-fro oscillations of the eyes. GPR143 is the causative gene of ocular albinism type 1 (OA1), which is a special type of INS that manifests as reduced vision, nystagmus, and iris and fundus hypopigmentation. Here, we explored the genetic spectrum of INS and the genotype-phenotype correlation.
A total of 98 families with INS from Southeast China were recruited for this study. A sample from each participant was subjected to PCR-based DNA direct sequencing of GPR143. Varied bioinformatics analysis was subsequently used in a mutation assessment. All participants received detailed ophthalmic examinations.
Genetic analysis identified 11 GPR143 mutations in 11.2% (11/98) of the X-linked INS families. These included seven novel mutations (c.899 C>T, c.886-2 A>G, c.1A>G, c.633_643del CCTGTTCCAAA, c.162_198delCGCGGGCCCCGGGTCCCCCGCGACGTCCCCGCCGGCC, c.628C>A, and c.178_179insGGGTCCC) and four known mutations. Patients who carried a GPR143 mutation were found to present a typical or atypical phenotype of OA1. All patients with GPR143 mutations manifested foveal hypoplasia; thus, about 45.8% (11/24) of the families with total X-linked INS exhibited foveal hypoplasia.
We discovered seven novel mutations and four previously reported mutations of GPR143 in a cohort of families with X-linked INS and enlarged the Chinese genetic spectrum of INS. These findings offer new insights for developing genetic screening strategies and shed light on the importance of conducting genetic analysis in confirming the clinical diagnosis in unresolved patients and atypical phenotypes.
A total of 98 families with INS from Southeast China were recruited for this study. A sample from each participant was subjected to PCR-based DNA direct sequencing of GPR143. Varied bioinformatics analysis was subsequently used in a mutation assessment. All participants received detailed ophthalmic examinations.
Genetic analysis identified 11 GPR143 mutations in 11.2% (11/98) of the X-linked INS families. These included seven novel mutations (c.899 C>T, c.886-2 A>G, c.1A>G, c.633_643del CCTGTTCCAAA, c.162_198delCGCGGGCCCCGGGTCCCCCGCGACGTCCCCGCCGGCC, c.628C>A, and c.178_179insGGGTCCC) and four known mutations. Patients who carried a GPR143 mutation were found to present a typical or atypical phenotype of OA1. All patients with GPR143 mutations manifested foveal hypoplasia; thus, about 45.8% (11/24) of the families with total X-linked INS exhibited foveal hypoplasia.
We discovered seven novel mutations and four previously reported mutations of GPR143 in a cohort of families with X-linked INS and enlarged the Chinese genetic spectrum of INS. These findings offer new insights for developing genetic screening strategies and shed light on the importance of conducting genetic analysis in confirming the clinical diagnosis in unresolved patients and atypical phenotypes.
摘要：
■婴儿眼震综合征（INS），或先天性眼球震颤（CN），是指一组以眼睛快速来回振荡为特征的眼部运动障碍。GPR143是眼白化病1型（OA1）的致病基因，这是一种特殊类型的INS，表现为视力下降，眼球震颤,虹膜和眼底色素减退.这里,我们探索了INS的遗传谱和基因型-表型相关性。
■本研究共招募了来自中国东南部的98个患有INS的家庭。对来自每个参与者的样品进行基于PCR的GPR143的DNA直接测序。随后在突变评估中使用各种生物信息学分析。所有参与者都接受了详细的眼科检查。
遗传分析在11.2%（11/98）的X连锁INS家族中鉴定出11个GPR143突变。其中包括七个新突变（c.899C>T，c.886-2A>G，c.1A>G，c.633_643delCCTGTTCCAAA，c.162_198delCGCGGGCCCCCCCCCGACGTCCCCCCCCGCCGCCGCCGCCGGCC，c.628C>A，和c.178_179insGGGTCCC）和四个已知的突变。发现携带GPR143突变的患者表现出OA1的典型或非典型表型。所有GPR143突变患者均表现为中央凹发育不全；因此，总X连锁INS的家庭中约有45.8％（11/24）出现中央凹发育不全。
■我们在一组X连锁INS家族中发现了GPR143的七个新突变和四个先前报道的突变，并扩大了INS的中国遗传谱。这些发现为开发遗传筛查策略提供了新的见解，并阐明了进行遗传分析在确认未解决患者和非典型表型的临床诊断中的重要性。
■本研究共招募了来自中国东南部的98个患有INS的家庭。对来自每个参与者的样品进行基于PCR的GPR143的DNA直接测序。随后在突变评估中使用各种生物信息学分析。所有参与者都接受了详细的眼科检查。
遗传分析在11.2%（11/98）的X连锁INS家族中鉴定出11个GPR143突变。其中包括七个新突变（c.899C>T，c.886-2A>G，c.1A>G，c.633_643delCCTGTTCCAAA，c.162_198delCGCGGGCCCCCCCCCGACGTCCCCCCCCGCCGCCGCCGCCGGCC，c.628C>A，和c.178_179insGGGTCCC）和四个已知的突变。发现携带GPR143突变的患者表现出OA1的典型或非典型表型。所有GPR143突变患者均表现为中央凹发育不全；因此，总X连锁INS的家庭中约有45.8％（11/24）出现中央凹发育不全。
■我们在一组X连锁INS家族中发现了GPR143的七个新突变和四个先前报道的突变，并扩大了INS的中国遗传谱。这些发现为开发遗传筛查策略提供了新的见解，并阐明了进行遗传分析在确认未解决患者和非典型表型的临床诊断中的重要性。
