• PMID: 22653751
• Gene Name: DPY19L2
• Condition: Globozoospermia
• Association: Associated
• Population size: 64
• Population details: 64 globozoospermic patients
• Sex: Male
• Infertility type: Male infertility
• Associated genes: DPY19L2
• Other associated phenotypes: Globozoospermia

Globozoospermia is mainly due to DPY19L2 deletion via non-allelic homologous recombination involving two recombination hotspots

Elinati E, Kuentz P, Redin C, Jaber S, Vanden Meerschaut F, Makarian J, Koscinski I, Nasr-Esfahani MH, Demirol A, Gurgan T, Louanjli N, Iqbal N, Bisharah M, Pigeon FC, Gourabi H, De Briel D, Brugnon F, Gitlin SA, Grillo JM, Ghaedi K, Deemeh MR, Tanhaei S, Modarres P, Heindryckx B, Benkhalifa M, Nikiforaki D, Oehninger SC, De Sutter P, Muller J, Viville S.

To date, mutations in two genes, SPATA16 and DPY19L2, have been identified as responsible for a severe teratozoospermia, namely globozoospermia. The two initial descriptions of the DPY19L2 deletion lead to a very different rate of occurrence of this mutation among globospermic patients. In order to better estimate the contribution of DPY19L2 in globozoospermia, we screened a larger cohort including 64 globozoospermic patients. Twenty of the new patients were homozygous for the DPY19L2 deletion, and 7 were compound heterozygous for both this deletion and a point mutation. We also identified four additional mutated patients. The final mutation load in our cohort is 66.7% (36 out of 54). Out of 36 mutated patients, 69.4% are homozygous deleted, 19.4% heterozygous composite and 11.1% showed a homozygous point mutation. The mechanism underlying the deletion is a non-allelic homologous recombination (NAHR) between the flanking low-copy repeats. Here, we characterized a total of nine breakpoints for the DPY19L2 NAHR-driven deletion that clustered in two recombination hotspots, both containing direct repeat elements (AluSq2 in hotspot 1, THE1B in hotspot 2). Globozoospermia can be considered as a new genomic disorder. This study confirms that DPY19L2 is the major gene responsible for globozoospermia and enlarges the spectrum of possible mutations in the gene. This is a major finding and should contribute to the development of an efficient molecular diagnosis strategy for globozoospermia. FAU - Elinati, Elias AU - Elinati E AD - Institut de Génétique et de Biologie Moléculaire et Cellulaire, Institut National de Santé et de Recherche Médicale (INSERM) U964, Centre National de Recherche Scientifique UMR1704, Université de Strasbourg, Illkirch 67404, France. FAU - Kuentz, Paul AU - Kuentz P FAU - Redin, Claire AU - Redin C FAU - Jaber, Sara AU - Jaber S FAU - Vanden Meerschaut, Frauke AU - Vanden Meerschaut F FAU - Makarian, Joelle AU - Makarian J FAU - Koscinski, Isabelle AU - Koscinski I FAU - Nasr-Esfahani, Mohammad H AU - Nasr-Esfahani MH FAU - Demirol, Aygul AU - Demirol A FAU - Gurgan, Timur AU - Gurgan T FAU - Louanjli, Noureddine AU - Louanjli N FAU - Iqbal, Naeem AU - Iqbal N FAU - Bisharah, Mazen AU - Bisharah M FAU - Pigeon, Frédérique Carré AU - Pigeon FC FAU - Gourabi, H AU - Gourabi H FAU - De Briel, Dominique AU - De Briel D FAU - Brugnon, Florence AU - Brugnon F FAU - Gitlin, Susan A AU - Gitlin SA FAU - Grillo, Jean-Marc AU - Grillo JM FAU - Ghaedi, Kamran AU - Ghaedi K FAU - Deemeh, Mohammad R AU - Deemeh MR FAU - Tanhaei, Somayeh AU - Tanhaei S FAU - Modarres, Parastoo AU - Modarres P FAU - Heindryckx, Björn AU - Heindryckx B FAU - Benkhalifa, Moncef AU - Benkhalifa M FAU - Nikiforaki, Dimitra AU - Nikiforaki D FAU - Oehninger, Sergio C AU - Oehninger SC FAU - De Sutter, Petra AU - De Sutter P FAU - Muller, Jean AU - Muller J