A rapidly progressive defective spermatogenesis in a Mexican family affected by spino-bulbar muscular atrophy

Abstract

Spino-bulbar muscular atrophy (SBMA) is an X-linked recessive adult progressive disorder affecting motor neurons. It is caused by a poly-glutamine tract expansion in the androgen receptor (AR) which generates protein aggregates that cannot be processed by proteasomes. A secondary mild androgen resistance is developed by AR dysfunction and patients present endocrine abnormalities including gynecomastia and poor function of testosterone in tissues; however, normally they are fertile. In this report we describe a Mexican family with three affected brothers with primary infertility caused by a progressive impairment of spermatogenesis leading to azoospermia before 40 years of age. They presented common features associated to patients affected by SMBA, such as gynecomastia, high level of CPK, muscle cramps, fasciculations, muscle wastage, and impaired swallowing. Two intracytoplasmic sperm injection (ICSI) cycles were performed in one of the patients resulting in fertilization failure. Molecular analysis of AR gene exon 1 revealed 54 CAG repeats in DNA extracted from leukocytes in affected patients and 22 repeats in the fertile non-affected brother. Severe impaired spermatogenesis of rapid progression has not been associated before to SBMA. This is the first report of assisted reproduction techniques indicated by male infertility in patients with this rare disorder. Further studies are required to confirm the unusual result of intracytoplasmic sperm injection cycles. We discuss the implications and possible pathogenesis of these unique features of SBMA in this family.