Published in August 2024, the article "A novel missense variant in PNLDC1 associated with nonobstructive azoospermia" discusses a new genetic mutation related to nonobstructive azoospermia, possibly causing faulty meiosis and spermatogenesis. The study was conducted by Mouness Rahimian, Masomeh Askari, and fellow genetics researchers.
The article states that approximately half of all infertility cases amongst couples are due to the male partner, the most common form being azoospermia. There are two types of azoospermia, obstructive (OA) and nonobstructive (NOA). This article focuses on nonobstructive, which has been associated with a number of genes. Through testing mice, the research team discovered that missing the PNLDC1 protein reduces testis size and causes infertility. In humans, the PNLDC1 gene is highly expressed in spermatocytes and having a mutated gene for the PNLDC1 protein results in NOA.
The bulk of the research involves clinical investigation of three men, all of whom were brothers, whose parents are first cousins. Blood samples were drawn, and then DNA isolation and sequencing was completed. A protein model for PNLDC1 was also created. The provided pedigree in the article shows that the infertile men received two copies of mutated recessive allele of the PNLDC1 gene. Siblings who were fertile had two wildtype alleles. A physical exam and karyotype analysis of the men showed normal results.
This was a recent publication that I personally found very interesting due to the clinical investigation subjects, who were all products of a consanguineous marriage. This resulted in three of the couple's children receiving mutated copies of a gene, which were seemingly recessive. This really goes to show that inbreeding depression is real, possible, and detectable even among a population as large and diverse as humans.
Another great reminder from this article--mutated genes make mutated mRNA, makes mutated proteins, makes mutated phenotypes. One single mishap in the DNA can be fatal. In this case, one missense mutation in a single gene results in infertility or other spermatogenic failure disease. While not so sure if this single gene is the cause of NOA, there is strong reason to believe that the gene and NOA are related.
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This article is super interesting! The connection between NOA and the condition being linked to inbreeding, as well as the fact that inbreeding typically results in gene mutations is so intriguing! Is the sterilization and infertility of the inbreeding nature, thus NOA, the body's way to try and avert future conception as well as prevent NOA from being passed down to offspring?
ReplyDeleteI also never knew that in the US, roughly half of the infertility cases among couples are due to the male partner.