Disorders of sex development
Gene: NR5A1
As discussed in the GMS Endocrinology Specialist Test Group webex call 28th Jan 2019: The Specialist Test Group agreed that there is enough evidence to rate this gene green.Created: 29 Apr 2019, 9:46 a.m.
Comment when marking as ready: Associated with phenotype in OMIM and G2P / DD. Thirteen variants reported in 46XY sex reversal 3 612965.Created: 12 Sep 2016, 10:53 a.m.
Comment on mode of inheritance: 46XY sex reversal 3 612965 and Premature ovarian failure 7 612964 are monogenic, Spermatogenic failure 8 613957 is biallelic and only on case of adrenocortical insufficiency has been reported to be associated with variants in this geneCreated: 12 Sep 2016, 10:41 a.m.
Nuclear receptor that is a key regulator of reproductive function. Usually heterozygous (monoallellic) changes that are de novo or sex limited dominant from a mother who sometimes then develops primary ovarian insufficiency. Very rarely recessive partial loss of function. Severe forms usually cause 46,XY female with uterus and primary adrenal insufficiency, but this is very rare. Most changes cause 46,XY atypical genitalia with or without Mulllerian structures and normal adrenal function. Milder defects can be found in association with hypospadias, male factor infertility, and in 46,XX females with primary ovarian insufficiency. Phenotypes may vary within families, and sex-limited dominant inheritance may mimic X-linked, so often misdiagnosed as partial androgen insensitivity syndrome.Created: 4 Feb 2016, 4:26 p.m.
Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Phenotypes
Variable underandrogenization, occassionally adrenal insfficiency; may also be associated with hypospadias, infertility or primary ovarian insufficinecy
Publications
Promoted to V1 21/12/2016
This gene has been classified as Green List (High Evidence).
Publications for NR5A1 were set to 26303087
Mode of inheritance for NR5A1 was changed to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Phenotypes for NR5A1 were set to Genital Anomalies and Suspected Adrenal Problems Gene Panel (UKGTN); Endocrine disorders including disorders of sexual development (Emory); 46XY sex reversal 3, 612965; Premature ovarian failure 7, 612964; Spermatogenic failure 8, 613957;
Phenotypes for gene NR5A1 were set to Genital Anomalies and Suspected Adrenal Problems Gene Panel (UKGTN); 46XY sex reversal 3, 612965; Premature ovarian failure 7, 612964; Spermatogenic failure 8, 613957; Endocrine disorders including disorders of sexual development (Emory)
NR5A1 was added to Disorders of sex developmentpanel. Source: Radboud University Medical Center, Nijmegen
NR5A1 was added to Disorders of sex developmentpanel. Source: Emory Genetics Laboratory
Model of inheritance for gene NR5A1 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
NR5A1 was added to Disorders of sex developmentpanel. Sources: UKGTN
NR5A1 was created by ellenmcdonagh