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- Barbaro, M, et al.
(författare)
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Partial deletion of the NR5A1 (SF1) gene detected by synthetic probe MLPA in a patient with XY gonadal disorder of sex development
- 2011
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Ingår i: Sexual development : genetics, molecular biology, evolution, endocrinology, embryology, and pathology of sex determination and differentiation. - : S. Karger AG. - 1661-5433. ; 5:4, s. 181-187
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Tidskriftsartikel (refereegranskat)abstract
- Steroidogenic factor 1 (SF1, officially NR5A1) is a nuclear receptor involved in adrenal and gonadal development. <i>NR5A1</i> mutations have been identified in patients with various forms of 46,XY disorders of sex development (DSD), including complete gonadal dysgenesis with or without adrenal insufficiency, mild testicular dysgenesis with ambiguous external genitalia or female external genitalia with clitoromegaly, and penoscrotal hypospadias. We developed a synthetic probe set for MLPA analysis of the <i>NR5A1</i> gene covering its 7 exons and analyzed 20 patients with 46,XY gonadal DSD in whom analyses failed to identify a genetic cause. We identified a partial <i>NR5A1</i> deletion affecting exons 2 and 3, leading to <i>NR5A1</i> haploinsufficiency in 1 patient presenting with female external genitalia with clitoromegaly, absence of a uterus, and mildly dysgenetic testes. This is the first partial <i>NR5A1</i> gene deletion identified by MLPA in a patient with 46,XY gonadal DSD. This finding stresses the importance of investigating copy number changes, even at the exon level, in genes involved in gonadal DSD. As <i>NR5A1</i> mutations can cause a wide spectrum of DSD with relatively high frequency, the analysis of the <i>NR5A1</i> gene by MLPA is quite important and should be extended to larger groups of patients.
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| 4. |
- Lee, PA, et al.
(författare)
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Global Disorders of Sex Development Update since 2006: Perceptions, Approach and Care
- 2016
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Ingår i: Hormone research in paediatrics. - : S. Karger AG. - 1663-2826 .- 1663-2818. ; 85:3, s. 158-180
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Tidskriftsartikel (refereegranskat)abstract
- The goal of this update regarding the diagnosis and care of persons with disorders of sex development (DSDs) is to address changes in the clinical approach since the 2005 Consensus Conference, since knowledge and viewpoints change. An effort was made to include representatives from a broad perspective including support and advocacy groups. The goal of patient care is focused upon the best possible quality of life (QoL). The field of DSD is continuously developing. An update on the clinical evaluation of infants and older individuals with ambiguous genitalia including perceptions regarding male or female assignment is discussed. Topics include biochemical and genetic assessment, the risk of germ cell tumor development, approaches to psychosocial and psychosexual well-being and an update on support groups. Open and on-going communication with patients and parents must involve full disclosure, with the recognition that, while DSD conditions are life-long, enhancement of the best possible outcome improves QoL. The evolution of diagnosis and care continues, while it is still impossible to predict gender development in an individual case with certainty. Such decisions and decisions regarding surgery during infancy that alters external genital anatomy or removes germ cells continue to carry risk.
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| 6. |
- Tack, LJW, et al.
(författare)
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Management of Gonads in Adults with Androgen Insensitivity: An International Survey
- 2018
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Ingår i: Hormone research in paediatrics. - : S. Karger AG. - 1663-2826 .- 1663-2818. ; 90:4, s. 236-246
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Tidskriftsartikel (refereegranskat)abstract
- <b><i>Background:</i></b> Complete and partial androgen insensitivity syndrome (CAIS, PAIS) are associated with an increased risk of gonadal germ cell cancer (GGCC). Recent guidelines recommend gonadectomy in women with CAIS in late adolescence. Nevertheless, many adult women prefer to retain their gonads. <b><i>Aims:</i></b> This study aims to explore attitudes towards gonadectomy in AIS in centres around the world, estimate the proportion of adults with retained gonads and/or who developed GGCC, and explore reasons for declining gonadectomy. <b><i>Methods:</i></b> A survey was performed among health care professionals who use the International DSD Registry (I-DSD). <b><i>Results:</i></b> Data were provided from 22 centres in 16 countries on 166 women (CAIS) and 26 men (PAIS). In CAIS, gonadectomy was recommended in early adulthood in 67% of centres; 19/166 (11.4%) women refused gonadectomy. Among 142 women who had gonadectomy, evidence of germ cell neoplasm in situ (GCNIS), the precursor of GGCC, was reported in 2 (1.4%) out of 8 from whom pathology results were formally provided. Nine out of 26 men with PAIS (34.6%) had retained gonads; 11% of centres recommended routine gonadectomy in PAIS. <b><i>Conclusion:</i></b> Although development of GGCC seems rare, gonadectomy after puberty is broadly recommended in CAIS; in PAIS this is more variable. Overall, our data reflect the need for evidence-based guidelines regarding prophylactic gonadectomy in AIS.
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