ESPE Abstracts (2015) 84 P-3-795

ESPE2015 Poster Category 3 DSD (31 abstracts)

Polymorphisms and Mutations of the Genes INSL3 and HOXD13 in the Pathogenesis of Isolated Cryptorchidism in Greece

Sofia Vappa a, , Christalena Sofocleous a, , Konstantinos Nikas d , Georgios Mastorakos e , Emmanouel Kanavakis a & Christina Kanaka-Gantenbein b

aDepartment of Medical Genetics, Medical School, University of Athens, Athens, Greece; bDivision of Endocrinology, Diabetes and Metabolism, First Department of Pediatrics, Medical School, University of Athens, Athens, Greece; cResearch Institute for the Study of Malignant Diseases in Childhood, University of Athens, Athens, Greece; dFirst Department of Pediatric Surgery, Aghia Sophia Children’s Hospital, Athens, Greece; eEndocrine Unit, Second Department of Obstetrics and Gynecology, Medical School, Athens University, Athens, Greece

Background: Current literature suggests an important role of both endocrine disruptors and genetic factors in the occurrence of cryptorchidism.

Objective and hypotheses: The aim of the study is to investigate the impact of variants in INSL3 and HOXD13 genes in the pathogenesis of isolated cryptorchidism in Greece. 43 boys with isolated cryptorchidism and 50 healthy non-cryptorchidic boys (control group) were enrolled.

Method: Genomic DNA was extracted from peripheral blood leukocytes and genetic analysis was conducted using PCR and direct sequencing of INSL3 and HOXD13 gene regions.

Results: Two apparently novel variants, the *−109 T>A of the INSL3 5′ UTR and the *528_529inv of the HOXD13 3’ UTR were disclosed in two unrelated patients. None of these variants was revealed in the control group (P=0.32304). Conversely, multiple previously described polymorphisms of both genes (INSL3: c.27G>A, c.126A>G and c.178A>G/HOXD13: c.*311C>T, c.*360A> T and c.*359_*360insT) were detected in both the cryptorchidic patients and the control group with no statistically significant difference between groups. ‘In silico’ analysis for the two as yet unreported findings indicated possible alterations of the cDNA sequences but with no comprehensible impact on the coding procedure. A combination of polymorphic alleles in these two genes was observed in both patients and controls without any statistically significant difference between groups (P=0.30873).

Conclusion: Neither the presence of specific polymorphisms in the INSL3 and HOXD13 genes, nor their combination could account for the pathogenesis of isolated cryptorchidism. The effect of endocrine disruptors or variations in non-examined genes in the pathogenesis of cryptorchidism, as well as the better delineation of the role of the new detected variants should be further investigated in larger populations.

Funding: Master Degree Course ‘Research on Female Reproduction’ taking place in Aretaeio General Hospital of Athens. Department of Medical Genetics of Choremio Research Laboratory.

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