Molekulargenetische Diagnostik
Praxis Dr. Mato Nagel

Störungen der Sexualentwicklung

Die Störungen der Sexualentwicklung umfasst eine Gruppe von Störungen bei der Herausbildung, Differenzierung und Funktion der Sexualorgane. Als Ursache findet sich meist eine gestörte Signaltransduktion.

Gliederung

Erbliche endokrinologische Erkrankungen
Autoimmune Polyendokrinopathie
Erbliche Erkrankungen der Hypophyse
Erkrankungen der Nebenschilddrüse
Hereditärer Diabetes insipidus
Nierenerkrankungen mit endokrinologischer Manifestation
Phäochromozytom
Störungen der Regulation des Wachstums
Störungen der Sexualentwicklung
Aplasie des Müllerschen Ganges und Hyperandrogenismus
WNT4
Denys-Drash-Syndrom
WT1
Hypogonadotropischer Hypogonadismus mit oder ohne Anosmie
FGF8
SERKAL-Syndrom
WNT4
Störungen des Schilddrüsenhormonsystems
Störungen des Steroidhormonsystems

Referenzen:

1.

Falardeau J et. al. (2008) Decreased FGF8 signaling causes deficiency of gonadotropin-releasing hormone in humans and mice.

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2.

Raivio T et. al. (2007) Reversal of idiopathic hypogonadotropic hypogonadism.

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3.

Taketo M et. al. (1995) Homologs of Drosophila Fushi-Tarazu factor 1 map to mouse chromosome 2 and human chromosome 9q33.

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4.

Luo X et. al. (1994) A cell-specific nuclear receptor is essential for adrenal and gonadal development and sexual differentiation.

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5.

Shen WH et. al. (1994) Nuclear receptor steroidogenic factor 1 regulates the müllerian inhibiting substance gene: a link to the sex determination cascade.

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6.

Oba K et. al. (1996) Structural characterization of human Ad4bp (SF-1) gene.

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7.

Wong M et. al. (1996) Cloning and sequence analysis of the human gene encoding steroidogenic factor 1.

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8.

Nachtigal MW et. al. (1998) Wilms' tumor 1 and Dax-1 modulate the orphan nuclear receptor SF-1 in sex-specific gene expression.

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9.

Harris AN et. al. (1998) The basic helix-loop-helix, leucine zipper transcription factor, USF (upstream stimulatory factor), is a key regulator of SF-1 (steroidogenic factor-1) gene expression in pituitary gonadotrope and steroidogenic cells.

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10.

Tremblay A et. al. (1999) Ligand-independent recruitment of SRC-1 to estrogen receptor beta through phosphorylation of activation function AF-1.

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11.

Hammer GD et. al. (1999) Phosphorylation of the nuclear receptor SF-1 modulates cofactor recruitment: integration of hormone signaling in reproduction and stress.

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12.

Achermann JC et. al. (1999) A mutation in the gene encoding steroidogenic factor-1 causes XY sex reversal and adrenal failure in humans.

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13.

None (1999) Gonadal and Extragonadal Functions of Ad4BP/SF-1: Developmental Aspects.

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14.

Biason-Lauber A et. al. (2000) Apparently normal ovarian differentiation in a prepubertal girl with transcriptionally inactive steroidogenic factor 1 (NR5A1/SF-1) and adrenocortical insufficiency.

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15.

Bland ML et. al. (2000) Haploinsufficiency of steroidogenic factor-1 in mice disrupts adrenal development leading to an impaired stress response.

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16.

Calvo RM et. al. (2001) Screening for mutations in the steroidogenic acute regulatory protein and steroidogenic factor-1 genes, and in CYP11A and dosage-sensitive sex reversal-adrenal hypoplasia gene on the X chromosome, gene-1 (DAX-1), in hyperandrogenic hirsute women.

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17.

Achermann JC et. al. (2002) Gonadal determination and adrenal development are regulated by the orphan nuclear receptor steroidogenic factor-1, in a dose-dependent manner.

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18.

Gizard F et. al. (2002) The transcriptional regulating protein of 132 kDa (TReP-132) enhances P450scc gene transcription through interaction with steroidogenic factor-1 in human adrenal cells.

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19.

Wilhelm D et. al. (2002) The Wilms tumor suppressor WT1 regulates early gonad development by activation of Sf1.

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20.

Tremblay JJ et. al. (2003) A mutated form of steroidogenic factor 1 (SF-1 G35E) that causes sex reversal in humans fails to synergize with transcription factor GATA-4.

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21.

Correa RV et. al. (2004) A microdeletion in the ligand binding domain of human steroidogenic factor 1 causes XY sex reversal without adrenal insufficiency.

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22.

Mallet D et. al. (2004) Gonadal dysgenesis without adrenal insufficiency in a 46, XY patient heterozygous for the nonsense C16X mutation: a case of SF1 haploinsufficiency.

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23.

Figueiredo BC et. al. (2005) Amplification of the steroidogenic factor 1 gene in childhood adrenocortical tumors.

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24.

Hasegawa T et. al. (2004) Testicular dysgenesis without adrenal insufficiency in a 46,XY patient with a heterozygous inactive mutation of steroidogenic factor-1.

[^]
25.

Lin L et. al. (2006) Analysis of DAX1 (NR0B1) and steroidogenic factor-1 (NR5A1) in children and adults with primary adrenal failure: ten years' experience.

[^]
26.

Kojima Y et. al. (2006) Role of transcription factors Ad4bp/SF-1 and DAX-1 in steroidogenesis and spermatogenesis in human testicular development and idiopathic azoospermia.

[^]
27.

Lin L et. al. (2007) Heterozygous missense mutations in steroidogenic factor 1 (SF1/Ad4BP, NR5A1) are associated with 46,XY disorders of sex development with normal adrenal function.

[^]
28.

Xue Q et. al. (2007) Transcriptional activation of steroidogenic factor-1 by hypomethylation of the 5' CpG island in endometriosis.

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29.

Köhler B et. al. (2008) Five novel mutations in steroidogenic factor 1 (SF1, NR5A1) in 46,XY patients with severe underandrogenization but without adrenal insufficiency.

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30.

Sekido R et. al. (2008) Sex determination involves synergistic action of SRY and SF1 on a specific Sox9 enhancer.

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31.

Lourenço D et. al. (2009) Mutations in NR5A1 associated with ovarian insufficiency.

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32.

Bashamboo A et. al. (2010) Human male infertility associated with mutations in NR5A1 encoding steroidogenic factor 1.

[^]
33.

Guran T et. al. (2016) Rare Causes of Primary Adrenal Insufficiency: Genetic and Clinical Characterization of a Large Nationwide Cohort.

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34.

Bashamboo A et. al. (2016) A recurrent p.Arg92Trp variant in steroidogenic factor-1 (NR5A1) can act as a molecular switch in human sex development.

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35.

Baetens D et. al. (2017) NR5A1 is a novel disease gene for 46,XX testicular and ovotesticular disorders of sex development.

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36.

Igarashi M et. al. (2017) Identical NR5A1 Missense Mutations in Two Unrelated 46,XX Individuals with Testicular Tissues.

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37.

Swartz JM et. al. (2017) A 46,XX Ovotesticular Disorder of Sex Development Likely Caused by a Steroidogenic Factor-1 (NR5A1) Variant.

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