Screening for Y chromosome microdeletions in childhood: lack of evidence for a direct association with testicular maldescent

Abstract

The aim of the study was to investigate the hypothesis that Y chromosome microdeletions are directly implicated in testicular maldescent. Genomic DNA was extracted from the peripheral blood of 292 subjects. This population consisted of (i) 180 children with all phenotypes of isolated (non-syndromic) testicular maldescent from 174 index families, (ii) affected adult relatives available (n = 12) and (iii) 100 unrelated children with normal external genitalia (controls). The sequence-tagged site primer set and the conditions of conventional polymerase chain reaction amplification were based on the current laboratory guidelines for molecular diagnosis of Y chromosome microdeletions recommended by the European Academy of Andrology and the European Molecular Genetics Quality Network. Two multiplex reactions were designed to screen the regions of azoospermic factors a, b and c. Each multiplex reaction included adequate internal and external amplification controls. Amplification products were submitted to electrophoresis on 2% agarose gel impregnated with ethidium bromide dye solution for 80 volt-h and visualised under ultraviolet light. No microdeletions were detected in any subject. These results indicate that Y chromosome microdeletions are not directly implicated in the pathogenesis of testicular maldescent. Other factors should be investigated to potentially explain the genetic predisposition that seems to exist in at least a subgroup of these patients.

Testicular Descent

“…1,4,5 The role of several genetic factors, including Insulin-like 3 (INSL3) gene alterations, has recently been evaluated in a large study conducted at our institutions. [6][7][8] In line with other studies, it was concluded that known genetic factors are responsible for only a small proportion of TD impairment 3 and that novel candidate factors should be sought. [6][7][8] The aim of the present review is to summarize current knowledge on normal TD in the human, including evolutionary aspects and interspecies differences.…”

“…91,134 The mechanism (direct or indirect) of androgenic action on the gubernaculum is controversial. It seems quite possible that androgens act indirectly 7 on the gubernaculum to mediate ISTD. AR localization studies in humans have demonstrated the presence of the receptor in the cremaster muscle but not in the gubernaculum.…”

Genetic analysis of the human Insulin-like 3 gene: absence of mutations in a Greek paediatric cohort with testicular maldescent

“…A total of 220 subjects derived from a previously described population (Mamoulakis et al ., , ) participated in the study. Patient population included 170 unrelated children with both testes present and at least one of them maldescended, exhibiting all phenotypes of nonsyndromic TMD.…”

Estudo de microdeleções do cromossomo Y em indivíduos com disgenesia gonadal e linhagem celular 46,XY

“…Assim, outras linhas de investigação relacionadas a microdeleções do cromossomo Y passaram a ser desenvolvidas. Um exemplo disso é um estudo publicado em 2012 no qual o material genético de 180 meninos com criptorquidia foi analisado por meio da técnica de PCR Multiplex; nesse estudo não se encontrou associação entre microdeleções em Yq11 e falha na descida do testículo para a bolsa escrotal [60].…”