Identification of Two Heterozygous Mutations in A Cryptozoospermic Patient and a De-novo Mutation in a Boy with Testicular Failure Born By IVF-ICSI
2National Institute of Biotechnology in the Negev, Ben-Gurion University of the Negev, Israel
3Fertility and IVF Unit, Department of Obstetrics and Gynecology, Soroka University Medical Center, Israel
4Faculty of Health Sciences, Ben-Gurion University of the Negev, Israel
5Pediatric Endocrinology Unit, Soroka University Medical Center, Israel
6School of Medicine, Ariel University, Israel
Introduction:
About half of the unexplained Cryptozoospermia and underdeveloped male traits are caused by genetic defects.
Objective:
Identify the genetic causes of an adult male`s Cryptozoospermia and a child with abnormal reproductive system, born following Intra Cytoplasmic Sperm Injection (ICSI) due to his father`s severe oligozoospermia.
Methods:
DNA was extracted from the patient`s blood and analyzed by Whole Exome Sequencing using bioinformatic tools. Sanger sequencing validated the WES findings.
Results:
In the adult patient, we identified a novel heterozygote frameshift mutation in the SYCP2 gene, which is essential role in meiosis. Previous studies showed that heterozygote mutations in this gene could cause low sperm count. Additionally, we detected two heterozygote frameshift mutations in ADAM20. ADAM20 encodes a membrane protein involved in sperm-oocyte fusion. Since the couple underwent an ICSI procedure, the mutations in ADAM20 had no effect.Pregnancy was achieved, and a healthy baby girl was born.
After birth, the boy presented as micropenis and undescended testis. Bilateral orchiopexy preformed at the age of 2 revealed a small undeveloped testis. After testosterone replacement therapy, at 15 years old, he has micropenis and descendent testis. We identified a known heterozygous missense mutation in the DHX37 gene, encoding a DEAH-box RNA helicase previously reported to result in this phenotype. The parent`s DNA availability enabled us to determine that the mutation appeared de-novo since it was absent in either parent.
Conclusion:
As probably in many idiopathic male infertility cases, genetic testing could identify the causes of the disruption in patients and lead to better fertility counseling.