Detection of pathogenic variants in four patients with globozoospermia
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目的 对4例圆头精子症患者的致病基因进行分析，明确其遗传学病因。 方法 选取2017年6月至2020年9月在中国人民解放军联勤保障部队第九〇〇医院被确诊为圆头精子症的4例患者作为研究对象，采集其精液和血液样本，进行精子浓度、活力、存活率、形态等常规检测以及精子顶体抗原CD46免疫荧光检测，提取外周血样基因组DNA进行全外显子组测序(WES)，对疑似致病变异通过Sanger测序进行验证。 结果 WES检测显示4例患者均携带DPY19L2基因变异，其中患者1 ~ 3携带DPY19L2基因纯合缺失，Sanger测序显示患者3在重组断裂点区域BP2存在断裂，通过非等位基因同源重组造成DPY19L2基因完全缺失。患者1存在第2 ~ 22外显子纯合缺失，患者2存在第14 ~ 15外显子纯合缺失，患者1和2的缺失既往未见文献报道，患者4为DPY19L2基因杂合缺失，且3′ UTR区存在罕见的纯合缺失。 结论 DPY19L2基因变异可能导致的圆头精子症的发生，其方式符合常染色体隐性遗传，同时也符合基因组病的特点。 Objective To explore the genetic basis for 4 patients with globozoospermia. Methods Semen and blood samples were collected from the patients for the determination of sperm concentration, viability, survival rate, morphology and acrosome antigen CD46. Meanwhile, DNA was extracted for whole exome sequencing (WES), and candidate variants were validated by Sanger sequencing. Results All of the four patients were found to harbor variants of the DPY19L2 gene. Patients 1 ~ 3 had homozygous deletions of the DPY19L2 gene. Sanger sequencing confirmed that the DPY19L2 gene in patient 3 was disrupted at a recombination breakpoint area BP2, resulting in nonallelic homologous recombination and complete deletion of the DPY19L2 gene. Patients 2 and 3 respectively harbored novel homozygous deletions of exons 2 ~ 22 and exons 14 ~ 15. Patient 4 harbored heterozygous deletion of the DPY19L2 gene, in addition with a rare homozygous deletion of the 3′ UTR region. Conclusion DPY19L2 gene variants probably underlay the globozoospermia in the four patients, which has fit an autosomal recessive pattern of inheritance and the characteristics of genomic diseases.
Objective To explore the genetic basis for 4 patients with globozoospermia. Methods Semen and blood samples were collected from the patients for the determination of sperm concentration, viability, survival rate, morphology and acrosome antigen CD46. Meanwhile, DNA was extracted for whole exome sequencing (WES), and candidate variants were validated by Sanger sequencing. Results All of the four patients were found to harbor variants of the DPY19L2 gene. Patients 1 ~ 3 had homozygous deletions of the DPY19L2 gene. Sanger sequencing confirmed that the DPY19L2 gene in patient 3 was disrupted at a recombination breakpoint area BP2, resulting in nonallelic homologous recombination and complete deletion of the DPY19L2 gene. Patients 2 and 3 respectively harbored novel homozygous deletions of exons 2 ~ 22 and exons 14 ~ 15. Patient 4 harbored heterozygous deletion of the DPY19L2 gene, in addition with a rare homozygous deletion of the 3′ UTR region. Conclusion DPY19L2 gene variants probably underlay the globozoospermia in the four patients, which has fit an autosomal recessive pattern of inheritance and the characteristics of genomic diseases.
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