Duan Wenhua, Zhou Taicheng, Huang Xiaoru, He Dongqiong, Hu Min
The First People's Hospital of Yunnan Province (The Affiliated Hospital of Kunming University of Science and Technology), Kunming, Yunnan Province, China.
The Affiliated Hospital of Yunnan University (The Second People's Hospital of Yunnan Province), Kunming, Yunnan Province, China.
BMC Med Genomics. 2025 Jan 7;18(1):4. doi: 10.1186/s12920-024-02078-0.
To explore possible pathogenic genes for concomitant exotropia using whole-exome sequencing.
In this study, 47 individuals from 10 concomitant exotropia (including intermittent exotropia and constant exotropia) pedigrees were enrolled. Whole-exome sequencing was used to screen mutational profiles in 25 affected individuals and 10 unaffected individuals. Sanger sequencing and in silico analysis were performed for all participants. Two target genes were used to capture the sequences of 220 sporadic samples.
All 10 concomitant exotropia pedigrees presented autosomal dominant inheritance with childhood onset (3.35 ± 1.51 years old). Eleven different missense variants were identified among seven potential pathogenic genes (COL4A2, SYNE1, LOXHD1, AUTS2, GTDC2, HERC2 and CDH3) that cosegregated with pedigree members. All variants were predicted to be deleterious and had low frequencies in the general population. Distinct variants of COL4A2 were present in three pedigrees, and distinct variants of SYNE1 were present in two pedigrees. Fifteen variants in AUTS2 and four variants in GTDC2 were identified in 220 patients with sporadic concomitant exotropia using a target-capture sequencing approach.
This is the first study to explore the genetic mechanism of concomitant exotropia and identify seven associated genes (COL4A2, SYNE1, LOXHD1, AUTS2, GTDC2, HERC2 and CDH3) that may be candidate genes causing concomitant exotropia. More samples and in-depth studies are needed to verify these findings.
采用全外显子组测序探索共同性外斜视可能的致病基因。
本研究纳入了来自10个共同性外斜视（包括间歇性外斜视和恒定性外斜视）家系的47名个体。利用全外显子组测序筛选25名患病个体和10名未患病个体的突变谱。对所有参与者进行Sanger测序和计算机分析。使用两个靶基因捕获220份散发样本的序列。
所有10个共同性外斜视家系均呈现常染色体显性遗传，发病于儿童期（3.35±1.51岁）。在7个潜在致病基因（COL4A2、SYNE1、LOXHD1、AUTS2、GTDC2、HERC2和CDH3）中鉴定出11种不同的错义变异，这些变异与家系成员共分离。所有变异预计均有害，且在普通人群中频率较低。COL4A2的不同变异存在于3个家系中，SYNE1的不同变异存在于2个家系中。使用靶标捕获测序方法在220例散发型共同性外斜视患者中鉴定出AUTS2的15种变异和GTDC2的4种变异。
这是首次探索共同性外斜视遗传机制并鉴定出7个相关基因（COL4A2、SYNE1、LOXHD1、AUTS2、GTDC2、HERC2和CDH3）的研究，这些基因可能是导致共同性外斜视的候选基因。需要更多样本和深入研究来验证这些发现。
