一例由DNAH5基因变异所致的原发性纤毛不动综合征

Analysis of a patient with primary ciliary dyskinesia caused by DNAH5 variants

目的探讨1例原发性纤毛不动综合征患者的遗传学机制。方法应用高通量测序和生物信息学分析检测患者的致病变异,用Sanger测序法对其家族成员进行验证,采用短效长方案行胞浆内单精子注射(intracytoplasmic single sperm injection,ICSI)助孕。结果患者存在梗阻性无精子症,鼻呼出一氧化氮值84 ppb,鼻窦及双肺存在原发性纤毛不动综合证的典型表现。测序发现其携带DNAH5基因第11外显子c.1489C>T(p.Q497X)和第38外显子c.6304C>T(p.R2102C)双等位基因变异。患者通过ICSI助孕获得临床妊娠。结论上述发现丰富了DNAH5基因的变异谱。DNAH5基因的变异不影响ICSI助孕的结局。

Objective To explore the genetic basis for a patient with primary ciliary dyskinesia(PCD).Methods High-throughput sequencing and bioinformatic analysis were carried out to identify pathogenic variant in the patient.Suspected variant was verified by Sanger sequencing among the family members,and intracytoplasmic sperm injection(ICSI)was used to achieve the pregnancy.Results The patient had obstructive azoospermia,measurement of nasal NO exhalation at 84 ppb,and typical symptoms of PCD in nasal sinuses and lungs.DNA sequencing showed that he had carried biallelic variants of the DNAH5 gene,namely c.1489C>T(p.Q497X)in exon 11 and c.6304C>T(p.R2102C)in exon 38.His wife achieved clinical pregnancy with the assistance of ICSI.Conclusion Above finding has enriched the spectrum of DNAH5 gene variants,though the latter did not affect the outcome of pregnancy by ICSI.