A case of germline mosaicism for a 7q32.1q33 deletion in a sperm donor: consequences on pregnancy follow-up and recommendations

Basic and Clinical Andrology

Alexandra Benachi¹  Aline Receveur²  Gerard Tachdjian³  Francois Michael Petit⁴  Veronique Drouineaud⁵  Celine Chalas⁵  Catherine Patrat⁶  Nelly Frydman⁷  Nathalie Massin⁸ 

[1] Faculté de médecine de Bicêtre, Université Paris-Saclay, F-94270, Le Kremlin Bicêtre, France;Service de gynécologie et obstétrique, Hôpital Antoine Béclère, AP-HP, Université Paris Saclay, cedex, F-92141, Clamart, France;Laboratoire de cytogénomique, Hôpital Antoine Béclère, AP-HP, Université Paris Saclay, cedex, F-92141, Clamart, France;Laboratoire de cytogénomique, Hôpital Antoine Béclère, AP-HP, Université Paris Saclay, cedex, F-92141, Clamart, France;Laboratoire d’Histologie-Embryologie-Cytogenetique- CECOS, Hôpital Antoine Béclère, AP-HP, Université Paris Saclay, cedex, F-92141, Clamart, France;Faculté de médecine de Bicêtre, Université Paris-Saclay, F-94270, Le Kremlin Bicêtre, France;Laboratoire de génétique moléculaire, Hôpital Antoine Béclère, AP-HP, Université Paris Saclay, cedex, F-92141, Clamart, France;Laboratoire d’Histologie-Embryologie-Biologie de la Reproduction - CECOS, Hôpital Cochin, AP-HP, Centre Université de Paris, F-75014, Paris, France;Laboratoire d’Histologie-Embryologie-Biologie de la Reproduction - CECOS, Hôpital Cochin, AP-HP, Centre Université de Paris, F-75014, Paris, France;Université de Paris, U 1016, Institut Cochin, F-75014, Paris, France;Laboratoire d’Histologie-Embryologie-Cytogenetique- CECOS, Hôpital Antoine Béclère, AP-HP, Université Paris Saclay, cedex, F-92141, Clamart, France;Faculté de médecine de Bicêtre, Université Paris-Saclay, F-94270, Le Kremlin Bicêtre, France;Service de gynécologie et obstétrique, Centre Hospitalier Intercommunal, F-94010, Créteil, France;

关键词: Germline mosaicism;    Chromosomal rearrangement;    FISH;    Spermatozoa;    Sperm donation;    Mosaïque germinale;    Réarrangement chromosomique;    Spermatozoïde;    Don de spermatozoïdes;   

DOI  :  10.1186/s12610-020-00113-5

来源: Springer

【 摘 要 】

BackgroundGermline mosaicism is considered to be a rare event. However, its occurrence is underestimated due to the limited availability of germ cells. The genomic variations that underlie this phenomenon comprise single nucleotide polymorphism (SNPs), copy number variations (CNVs) and aneuploidies. In the case of CNVs, deletions are more frequent in the paternal germline while duplications are more commonly maternal in origin. Germline mosaicism increases with paternal age as the risk of SNPs increase with the number of germ cell divisions. We here report a case of germline mosaicism in the spermatozoa of a donor that resulted in one pathological pregnancy.ResultsStraws from the same sperm donor were provided to seven recipient couples, resulting in four pregnancies. Second trimester ultrasound analysis revealed bilateral talipes equinovarus associated with growth retardation in one of these pregnancies. Array-comparative genomic hybridization (CGH) carried out after amniocentesis revealed a 4 Mb deletion in the 7q32.1q33 region. The blood karyotypes and array-CGHs were normal in the mother, as well as in the donor. However, the microsatellite profile indicated a paternal origin. Fluorescent in situ hybridization (FISH) analysis of the donor’s spermatozoa revealed the same chromosomal rearrangements in 12% of the spermatozoa population. Due to the documented risk of mental retardation associated with genomic rearrangements in the same region, the couple decided to terminate the pregnancy. Amniocentesis was performed in the other couples, which yielded normal FISH analysis results.ConclusionsSeveral cases of germline mosaicism have been reported to date, but their frequency is probably underestimated. Moreover, it is important to note that germline mosaicism cannot be ruled out by conventional cytogenetic screening of blood cells. This case highlights the need for close follow-up of every pregnancy obtained through gamete donation, given that the occurrence of germline mosaicism may have major consequences when multiple pregnancies are obtained concomitantly.

【 授权许可】

CC BY