After two-year-long investigations, the group has been able to identify a high number of one specific mutation in M1AP within the European population that is probably traceable to a founder’s mutation in the genome of the original ancestor. Based on DNA sequencing data of almost 2,000 infertile men with M1AP mutations in both parental gene copies the group found four patients from Münster, five members of a consanguineous Turkish family, two cases from Portugal, and one patient each from Gießen, Nijmegen, and Newcastle upon Tyne, respectively. Thus, overall, these mutations represent a relatively frequent cause of autosomal recessive severe spermatogenic failure and male infertility with strong clinical validity. Thus, M1AP achieves a high level of evidence immediately upon publication.
As of now, no effective causal treatment could be found that raises affected patients’ chances of conceiving a child. In this regard, testicular biopsy and subsequent artificial reproduction did not entail significant improvements in male fertility given the patients’ low probability of carrying spermatozoa in the semen or spermatids in the testis. Still, an enhanced understanding for genetic causes for infertility in men, who often have an alleviated sense of guilt, as well as improved genetic counseling, will continue to benefit future treatment. Hence, sequencing of the M1AP gene will be incorporated as part of routine genetic diagnostics immediately.
Written by: Frank Tüttelmann, Institute of Human Genetics, University of Münster; Margot Wyrwoll, Institute of Human Genetics, University of Münster; and Corinna Friedrich, Institute of Human Genetics, University of Münster.
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