Biallelic variants in DNAH11 cause male infertility with asthenozoospermia in a Chinese non-consanguineous family: A case report

DNAH11基因双等位基因变异导致中国非近亲结婚家庭男性患有弱精子症性不育:病例报告

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Abstract

RATIONALE: Asthenozoospermia (AZS), a leading cause of male infertility, frequently results from genetic defects that disrupt flagellar assembly. Mutations in the DNAH11 gene can cause abnormal dynein arm structures, leading to AZS and impaired male fertility. However, current evidence regarding DNAH11 mutations in male infertility remains limited, warranting further exploration of their pathogenic mechanisms. PATIENT CONCERNS: A 35-year-old Chinese male presented with primary infertility and AZS. DIAGNOSES: Whole-exome sequencing was performed on the proband to identify the potential genetic etiology, followed by Sanger sequencing validation of candidate variants in both the proband and his parents. A novel compound heterozygous mutation in the DNAH11 gene - comprising a frameshift mutation (c.1174del) and a splicing mutation (c.3766-8A > G) - was identified in the proband. Sanger sequencing confirmed paternal inheritance of the c.1174del mutation and maternal inheritance of the c.3766-8A > G mutation. INTERVENTIONS: After receiving genetic counseling, the patient chose to undergo intracytoplasmic sperm injection (ICSI) treatment. OUTCOMES: The ICSI procedure did not result in a successful clinical pregnancy. Follow-up outcomes will continue to be monitored. LESSONS: This study identified novel biallelic DNAH11 variants associated with reduced sperm motility, expanding the known mutational spectrum of DNAH11 variants implicated in AZS and providing additional evidence for genetic counseling and diagnosis.

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