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Background <p><i>CFAP57</i> is essential for the development and function of sperm flagella, as it is required for the assembly and stability of the inner dynein arm (IDA) that drive sperm motility. Mutations in <i>CFAP57</i> have been associated with multiple morphological abnormalities of the sperm flagella (MMAF), a leading cause of male infertility. Both human and mouse studies have shown that the loss of <i>CFAP57</i> protein disrupts IDA assembly, impairing sperm motility. However, the genetic causes remain unknown in many MMAF cases, highlighting the importance of identifying additional mutations.</p> Materials and methods <p>In this study, we examined a consanguineous Emirati family with a male patient clinically diagnosed with asthenozoospermia. Semen analysis revealed abnormalities in sperm motility and morphology. Saliva and peripheral blood samples were collected, from which genomic DNA was extracted and subjected to whole-exome sequencing (WES). Sanger sequencing was performed to confirm the segregation of candidate variants within the family.</p> Results <p>WES revealed a novel homozygous nonsense mutation in <i>CFAP57</i> (c.3223&#xa0;C &gt; T; p.Arg1075Ter), located within a large homozygous region on chromosome 1. Sanger sequencing confirmed the segregation of the variant within the family; the proband was homozygous for the mutation, while both parents were heterozygous carriers. Semen analysis showed that 63% of sperm were immotile and only 4% had normal morphology, consistent with an MMAF phenotype. Notably, the patient exhibited no signs of primary ciliary dyskinesia (PCD), suggesting that the mutation selectively affects the sperm-specific isoform of <i>CFAP57</i>.</p> Discussion <p>This study identifies a novel <i>CFAP57</i> mutation associated with MMAF, expanding the mutational spectrum of the gene and supporting its potential role in male infertility, which warrants further investigation in larger cohorts.</p>

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A novel CFAP57 nonsense mutation causes asthenozoospermia in a consanguineous Emirati family

  • 期刊论文

  • 发表日期：

    2026年3月7日

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  • Abdelaziz Tlili,
  • Ahlam Kaddoura,
  • Jihen Chouchen

摘要

Background

CFAP57 is essential for the development and function of sperm flagella, as it is required for the assembly and stability of the inner dynein arm (IDA) that drive sperm motility. Mutations in CFAP57 have been associated with multiple morphological abnormalities of the sperm flagella (MMAF), a leading cause of male infertility. Both human and mouse studies have shown that the loss of CFAP57 protein disrupts IDA assembly, impairing sperm motility. However, the genetic causes remain unknown in many MMAF cases, highlighting the importance of identifying additional mutations.

Materials and methods

In this study, we examined a consanguineous Emirati family with a male patient clinically diagnosed with asthenozoospermia. Semen analysis revealed abnormalities in sperm motility and morphology. Saliva and peripheral blood samples were collected, from which genomic DNA was extracted and subjected to whole-exome sequencing (WES). Sanger sequencing was performed to confirm the segregation of candidate variants within the family.

Results

WES revealed a novel homozygous nonsense mutation in CFAP57 (c.3223 C > T; p.Arg1075Ter), located within a large homozygous region on chromosome 1. Sanger sequencing confirmed the segregation of the variant within the family; the proband was homozygous for the mutation, while both parents were heterozygous carriers. Semen analysis showed that 63% of sperm were immotile and only 4% had normal morphology, consistent with an MMAF phenotype. Notably, the patient exhibited no signs of primary ciliary dyskinesia (PCD), suggesting that the mutation selectively affects the sperm-specific isoform of CFAP57.

Discussion

This study identifies a novel CFAP57 mutation associated with MMAF, expanding the mutational spectrum of the gene and supporting its potential role in male infertility, which warrants further investigation in larger cohorts.