Evaluation of The 1499T>C Variant in The AKAP3 Gene of Infertile Men with Multiple Morphological Abnormalities of The Sperm Flagella Phenotype: A Case-Control Study

Document Type : Original Article


1 Department of Genetics, Reproductive Biomedicine Research Center, Royan Institute for Reproductive Biomedicine, ACECR, Tehran, Iran

2 Department of Andrology, Reproductive Biomedicine Research Center, Royan Institute for Reproductive Biomedicine, ACECR, Tehran, Iran

3 Department of Pathology and Laboratory Medicine, Western University, London, Ontario, Canada

4 Molecular Genetics Laboratory, Molecular Diagnostics Division, London Health Sciences Centre, London, Ontario, Canada


Background: Infertile men with multiple morphological abnormalities of the sperm flagella (MMAF) phenotype
exhibit mosaic sperm flagella abnormalities such as short, bent, coiled, and irregular flagella or absent flagella. Sperm
flagellum has an ultrastructurally axonemal structure that contains a large number of proteins. A-Kinase Anchoring
Protein 3 (AKAP3) is expressed in spermatozoa. It may function as a regulator of motility and the acrosome reaction.
This study aimed to compare genetic changes in infertile men suffering MMAF phenotype with the control group.
Materials and Methods: In this case-control study, genetic variants of the AKAP3 gene were evaluated in 60 infertile
men with MMAF phenotype and 40 fertile men, as control. As exon five of the AKAP3 gene encodes the functional
domain of this protein, its genetic variants were studied. Therefore, polymerase chain reaction (PCR)-sequencing was
undertaken on the DNA extracted from control and patients’ blood samples.
Results: Sixty infertile men with MMAF phenotype and 40 normozoospermic men, as control, were enrolled in
this study. Four haplotype variants 1378T>C (rs10774251), 1391C>G (rs11063266), 1437T>C (rs11063265), and
1573G>A (rs1990312) were detected in all patients and controls. On the other hand, a missense mutation 1499T>C
(rs12366671) was observed in four patients with the homozygous form while seven patients carried the heterozygous
form. No mutation was identified in the controls (P=0.04). The difference between the variation allele frequencies was
assessed in the patient and control groups by the Fisher Exact Test.
Conclusion: In the homozygous form, this mutation changed Isoleucine to Threonine. This alternation occurred inside
the AKAP4 binding domain of the AKAP3 protein. The observed variants caused no significant deviation in the
secondary structure of AKAP3 protein and probably its function in spermatozoa flagella. So, these variants cannot be
considered as the causes of MMAF phenotype in the studied patients.


Main Subjects


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