A Case Series Of Infants With Increased Vamp7 Gene Dosage At Birth And Virilization Defects.

Summary Background Genitourinary disorders are the most frequent congenital defects in newborns, however little is known about their etiology. Several studies have been carried out to find genetic risk factors in the development of these malformations. The expression of VAMP7 is found in testes, epididymis, seminal vesicles, prostatic tissues, penis and urethra. Alterations in gene dose of VAMP7 were recently reported in a subset of male patients initially identified clinically by the presence of congenital genitourinary disorders. In 2016, we developed a diagnostic algorithm for early detection of sex chromosome aneuploidies by quantifying the SHOX, VAMP7 and SRY gene dose in newborns by qPCR using dried blood spot (DBS) samples. Objective Correlate the increased gene dose of VAMP7, obtained by qPCR using dried blood spot (DBS), with genitourinary congenital defects attributable to disorders in virilization and verify the increased gene dose by microarrays. Study design Samples that only presented increased VAMP7 gene dosage were selected from a previously analyzed group of 5,088 males in which the early detection of sex chromosomes aneuploidies was performed. Eight males were found with an increased gene dose of VAMP7 (RQ> 1.3) and were called in for a complete clinical evaluation aimed at the identification of genitourinary anomalies, qPCR and microarrays. Results Eight males from 5,088 samples, were identified with increased VAMP7 gene dosage of which six patients were clinically evaluated, of which 50% were identified with alterations in genital development (bilateral cryptorchidism, unilateral cryptorchidism and glandular hypospadias) and speech delay, while the rest presented different types of atopy. Discussion Tannour-Louet et al. postulated on 2014, that the duplication of the Xq28 region, specifically of VAMP7, plays a role in the human masculinization disorders of the urogenital tract. The study was based on aCGH results performed to 116 males with disorders of sexual differentiation. In the present study, the patients were initially selected due to an increased gene dose of VAMP7 detected by qPCR, then the clinical evaluation and the aCGH were performed, inverse to what was reported previously but with similar percentages between both studies. Conclusion In this work, we report cases of cryptorchidism, hypospadias, language delay and atopy in male preschoolers initially identified because they have an increased gene dose of VAMP7.