Maram Arafat
Ben-Gurion University of the Negev, Beer-Sheva, Israel
Title: A novel mutation causes Non Obstructive Azoospermia in infertile mentructive Azoospermia in infertile men
Biography
Biography: Maram Arafat
Abstract
Introduction: Infertility is defined as a failure of conception after 12 months of having unprotected intercourse, and male infertility accounts for 30–55% of infertile couples. Azoospermia, is diagnosed when sperm is completely absent in the ejaculate even after centrifugation.
Materials and Methods: Genotyping was done on four azoospermic individuals of a consanguineous Bedouin family and their parents. Exome sequencing was performed on the DNA of one patient.
Results: Assuming homozygosity of a recessive founder mutation as the likely cause of the disorder, we have genotyped 4 patients and their parents. We identified 5 shared homozygous regions larger than 2 cM, encompassing a total of 13.8Mbp on the autosomal chromosomes. In these regions only one homozygous variant with allele frequencies of less than 1% in the public databases (ExAc browser, 1000 Genomes and dbSNP) was identified. This variant segregated as expected in the family, with a calculated Lod score of 3.42. The variation was not present in 620 Bedouin controls.
The variation is a frameshift mutation in a gene encoding a protein demonstrated to be essential for silencing of Line-1 retrotransposon in the male germline. Using a commercial antibody to the N-terminus of the encoded protein, immunofluorescent studies demonstrated it is produced in patients' testes, especially in spermatogonial cells (mainly in the cytoplasm) and in spermatocysts/round spermatids (mainly in the nucleus).
Discussion: The identification of the mutation causing azoospermia enables accurate diagnosis in the enlarged family and demonstrates the importance of repressing retrotransposon activation in the male germline in human.