Biallelic mutations of CFAP74 may cause human primary ciliary dyskinesia and MMAF phenotype

J Hum Genet. 2020 Nov;65(11):961-969. doi: 10.1038/s10038-020-0790-2. Epub 2020 Jun 18.


Primary ciliary dyskinesia (PCD) is a rare genetic disorder characterized by recurrent respiratory infections, nasosinusitis, tympanitis, and/or male infertility, all of which can severely impair the patient's quality of life. Multiple morphological abnormalities of the sperm flagella (MMAF) is one type of severe teratozoospermia and results from a variety of flagellar defects. In this study, we conducted whole-exome sequencing to identify and evaluate the genetic lesions in two patients with potential PCD and MMAF. Biallelic mutations in exon 10, c.983G>A; p.(Gly328Asp), and exon 29, c.3532G>A; p.(Asp1178Asn), of the CFAP74 (NM_001304360) gene were identified in patient 1 (P1), and biallelic mutations in exon 7, c.652C>T; p.(Arg218Trp), and exon 35, c. 4331G>C; p.(Ser1444Thr), of the same gene were identified in patient 2 (P2). Bioinformatic analysis suggested that these variants may be disease causing. Immunofluorescence confirmed that CFAP74 was absent in these patients' sperm samples. Intracytoplasmic sperm injection (ICSI) was carried out for P1, and his wife became pregnant after embryo transfer and gave birth to a healthy baby. To the best of our knowledge, this study is the first to identify the importance of CFAP74 in potential PCD and MMAF, contributing to the genetic diagnosis of these disorders and helping to predict pregnancy outcomes relevant in in vitro fertilization.

MeSH terms

  • Abnormalities, Multiple / genetics*
  • Abnormalities, Multiple / pathology
  • Adult
  • Alleles
  • Ciliary Motility Disorders / complications
  • Ciliary Motility Disorders / genetics*
  • Ciliary Motility Disorders / pathology
  • Exome Sequencing
  • Female
  • Flagella / genetics
  • Flagella / pathology
  • Genetic Predisposition to Disease
  • Humans
  • Infertility, Male / complications
  • Infertility, Male / genetics*
  • Infertility, Male / pathology
  • Male
  • Mutation / genetics
  • Sperm Tail / metabolism
  • Sperm Tail / pathology
  • Spermatozoa / abnormalities
  • Spermatozoa / metabolism
  • Teratozoospermia / complications
  • Teratozoospermia / genetics*
  • Teratozoospermia / pathology