Mutation analysis of subjects with 46, XX sex reversal and 46, XY gonadal dysgenesis does not support the involvement of SOX3 in testis determination

Abstract

Despite the identification of an increasing number of genes involved in sex determination and differentiation, no cause can be attributed to most cases of 46, XY gonadal dysgenesis, approximately 20% of 46, XX males and the majority of subjects with 46, XX true hermaphroditism. Perhaps the most interesting candidate for involvement in sexual development is SOX3, which belongs to the same family of proteins (SOX) as SRY and SOX9, both of which are involved in testis differentiation. As SOX3 is the most likely evolutionary precursor to SRY, it has been proposed that it has retained a role in testis differentiation. Therefore, we screened the coding region and the 5' and 3' flanking region of the SOX3 gene for mutations by means of single-stranded conformation polymorphism and heteroduplex analysis in eight subjects with 46, XX sex reversal (SRY negative) and 25 subjects with 46, XY gonadal dysgenesis. Although no mutations were identified, a nucleotide polymorphism (1056C/T) and a unique synonymous nucleotide change (1182A/C) were detected in a subject with 46, XY gonadal dysgenesis. The single nucleotide polymorphism had a heterozygosity rate of 5.1% (in a control population) and may prove useful for future X-inactivation studies. The absence of SOX3 mutations in these patients suggests that SOX3 is not a cause of abnormal male sexual development and might not be involved in testis differentiation.

Abordagem citogenética e molecular em material de abortos espontâneos

“…Por ser método rápido e seguro para detectar aneuploidias, atual-mente a FISH tem sido cada vez mais utilizada como auxiliar da citogenética em diagnóstico prénatal e nos casos de aborto espontâneo. As sondas centroméricas habitualmente utilizadas são as dos cromossomos 13,18,21,16,22,15, X e Y 14,15 .…”

“…A técnica de FISH foi desenvolvida de acordo com os trabalhos de Eiben et al 14 18 Foram avaliadas as taxas de sucesso (obtenção de cariótipo) e falha (impossibilidade de obtenção de cariótipo) de cada uma das técnicas (citogenética, FISH e PCR). A taxa de sucesso de cada método foi calculada dividindo-se o número de amostras em que foi possível determinar o cariótipo pelo número total de amostras submetidas ao exame, multiplicando-se o resultado por cem.…”

Over- and Underdosage of SOX3 Is Associated with Infundibular Hypoplasia and Hypopituitarism

“…We identified no further changes and found no other expansions in the first PA tract in an additional 72 male patients with hypopituitarism. Previous data have shown no mutations within SOX3 in 56 patients with idiopathic oligo-/azoospermia and infertility (Raverot et al 2004); 15 patients with X-linked MR and two Australian families with hypopituitarism (Laumonnier et al 2002); 8 patients with 46,XX sex reversal and 25 patients with 46,XY gonadal dysgenesis (Lim et al 2000); and 10 patients with Xlinked Rett syndrome (Xiang et al 2000). Additionally, Laumonnier et al (2002) sequenced the PA tract in question in 600 normal chromosomes and found no changes.…”

Sry, more than testis determination?

“…Sox3 deletions in mice have abnormal development of diencephalon and anterior pituitary gland and lack differentiated spermatogonia (73). Sox3 has been speculated to activate Sox9 and induce sex reversal in XX transgenic mice, providing a similar outcome as Sry expression (4,51,92). If Sry and Sox3 can behave similarly in testis development, can they also behave similarly in the brain?…”