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Table 1.

Phenotype of the DSD patients harboring the NR5A1/SF-1 p.Gly146Ala variant.

Further details including biochemical data are given in S2 Table.

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Fig 1.

Algorithm of genetic workup.

A. Mode of genetic analysis, e.g. panel and whole exome sequencing (WES). Two patients were identified with pathogenic variants in LHCGR and AR by panel analysis and were not further analyzed by whole-exome sequencing (WES). B. Filtering algorithm of genetic data. Steps used for variant filtering after WES of eleven DSD patients harboring the NR5A1/SF-1 p.Gly146Ala variant are depicted (letters a to f). Final candidates and their possible impact are listed and characterized in Table 2 and S3 Table.

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Fig 2.

External genital phenotype of the 13 DSD patients harboring the NR5A1/SF-1 p.Gly146Ala variant shown with respect to their karyotype.

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Fig 3.

Genetic variants identified in 13 DSD patients harboring the NR5A1/SF-1 p.Gly146Ala variant illustrated with respect to the known pathways of male and female sex determination and differentiation.

The scheme shows an overview of involved genes and their currently assumed relationship to sexual development. Genes with variants identified by whole exome sequencing in the patients have specific colors. In dark blue: Candidate genes in patient 1; in brown: Candidate genes in patient 3; in green: Candidate genes in patient 6; in yellow: Candidate genes in patient 8; in red: Candidate genes in patient 9; in pink: Candidate genes in patient 10; in light blue: Candidate genes in patient 11; in purple: Candidate genes in patient 12; in orange: Candidate genes in patient 13; in dark grey: Known genes involved in sexual development. Interrogation mark (?): Function/timing/location is not clear; arrows: Activation; inhibitors: Inhibition; lines: Interaction/partnership; dashed lines/arrows: Hormone production.

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Fig 3 Expand

Table 2.

Additional gene variants identified in the DSD patients harboring the NR5A1/SF-1 p.Gly146Ala variant.

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Table 2 Expand