摘要目的:对既往在神经发育障碍患者中检出的 SLC9A7基因c.1042-10G>C(NM_001257291.2)半合子变异的临床意义进行评价，为家系产前遗传咨询提供依据。 方法:选取2022年12月至2024年7月就诊于河南省人民医院医学遗传中心的4个家系为研究对象。收集家系成员表型信息，采集家系成员生物样本提取基因组DNA，采用全外显子组测序和拷贝数变异检测鉴定可疑致病性变异，应用Sanger测序进行候选变异的家系共分离分析。通过反转录PCR分析候选变异携带者外周血RNA剪接模式，采用定量PCR分析 SLC9A7基因不同转录本在胎儿脑组织及外周血中的表达特征。结合美国医学遗传学与基因组学学会(ACMG)序列变异解读指南对候选变异进行致病性评级。本研究已通过河南省人民医院医学伦理委员会审查(批准号：2021-171)。 结果:在4个不同家系中共检出 SLC9A7基因c.1042-10G>C变异男性半合子个体6名，其中5名个体表型正常(3名成年男性和2名婴幼儿)；仅1例男性患儿(家系F1-Ⅲ 1)表现为全面发育迟缓、颈短小、颈蹼和眼球发育异常并先天性角膜白斑，该患儿有出生窒息史，且同时携带 HUWE1基因c.12283C>G半合子变异。 SLC9A7基因c.1042-10G>C(NM_001257291.2)变异杂合子个体和半合子个体的外周血RNA序列与健康个体一致，提示该变异不影响剪接。定量PCR检测提示胎脑组织和外周血中均以NM_001257291.2转录本的表达为主。 结论:SLC9A7基因c.1042-10G>C变异不影响RNA剪接且在多个表型正常男性中检出，为良性变异。

abstractsObjective:To evaluate the clinical significance of a hemizygous c. 1042-10G>C variant of the SLC9A7 gene NM_001257291.2) previously identified in individuals with neurodevelopmental disorders, and to provide an evidence-based guidance for prenatal genetic counseling. Methods:Four families presented at the Medical Genetics Center of Henan Provincial People′s Hospital between December 2022 and July 2024 were included in this study. Phenotypic information and biological samples were collected from family members. Genomic DNA was extracted and subjected to whole-exome sequencing and copy number variation analysis to identify candidate pathogenic variants. Sanger sequencing was performed for familial co-segregation analysis. Reverse-transcription PCR was used to assess the RNA splicing pattern of the variant in peripheral blood samples. Quantitative PCR was employed to analyze the expression profiles of various SLC9A7 transcripts in fetal brain tissue and peripheral blood samples. Pathogenicity of the variant was classified based on guidelines from the American College of Medical Genetics and Genomics (ACMG). This study was approved by the Medical Ethics Committee of Henan Provincial People′s Hospital (Ethics No.: 2021-171). Results:Six hemizygous males carrying the SLC9A7 c. 1042-10G>C variant were identified among the four families, which included three adult males and two male infants with normal phenotypes. Only one affected male from family 3 exhibited global developmental delay, short neck, webbed neck, ocular dysplasia, and congenital corneal leukoma. He also had a history of perinatal asphyxia and carried an additional hemizygous variant HUWE1 c. 12283C>G. Reverse-transcription PCR showed no aberrant splicing in heterozygous or hemizygous carriers compared to healthy controls, suggesting that the variant does not affect RNA splicing. Quantitative PCR revealed that NM_001257291.2 is the predominant transcript expressed in fetal brain tissue and peripheral blood. Conclusion:The SLC9A7 c. 1042-10G>C variant does not alter RNA splicing and is present in multiple phenotypically normal males, which supported its classification as a benign variant.