Novel Mutations in CFAP44 and CFAP43 Cause Multiple Morphological Abnormalities of the Sperm Flagella (MMAF)

Reprod Sci. 2019 Jan;26(1):26-34. doi: 10.1177/1933719117749756. Epub 2017 Dec 25.

Abstract

Multiple morphological abnormalities of the sperm flagella (MMAF) is a rare disease that causes primary infertility. However, the genetic causes for approximately half of MMAF cases are unknown. Whole exome sequencing analysis of the 27 patients with MMAF identified several CFAP44 mutations (3 homozygous: c.2935_2944del: p.D979*, c.T1769A: p.L590Q, c.2005_2006del: p.M669Vfs*13; and putative compound heterozygous: c.G3262A: p.G1088S and c.C1718A: p.P573H.) and CFAP43 acceptor splice-site deletion (c.3661-2A>-) mutations in 5 and 1 patients, respectively. Real-time quantitative polymerase chain reaction assays also demonstrated that CFAP44 expression was very weak in patient (P)1 and P3, and CFAP43 expression was lower in P6 than in the control. Immunofluorescence analysis of CFAP43 showed lower CFAP43 protein expression levels in P6 than in the normal control. This study demonstrated that biallelic mutations in CFAP44 and CFAP43 cause MMAF. These results provide researchers with a new insight to understand the genetic etiology of MMAF and to identify new loci for genetic counselling of MMAF.

Keywords: CFAP43; CFAP44; MMAF; consanguineous family; dysplasia of the fibrous sheath; multiple morphological abnormalities of the sperm flagella; whole exome sequencing.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Cytoskeletal Proteins
  • Exome Sequencing
  • Humans
  • Infertility, Male / genetics*
  • Infertility, Male / pathology
  • Male
  • Microtubule Proteins / genetics*
  • Mutation
  • Nuclear Proteins / genetics*
  • Peptide Hydrolases / genetics*
  • Sperm Tail / pathology*

Substances

  • CFAP43 protein, human
  • Cytoskeletal Proteins
  • Microtubule Proteins
  • Nuclear Proteins
  • CFAP44 protein, human
  • Peptide Hydrolases