Preferred Label : 46,xy sex reversal 1;
Symbol : SRXY1;
CISMeF acronym : SRVX; SRXY1; TDFX;
Type : Phenotype, molecular basis known;
Alternative titles and symbols : 46,xy sex reversal, sry-related; 46,xy gonadal dysgenesis, complete, sry-related;
Included titles and symbols : 46,xy true hermaphroditism, sry-related; Testis-determining factor, X-chromosomal; Sex-reversing locus on X; TDFX; SRVX;
Description : Individuals with 46,XY complete gonadal dysgenesis are phenotypically female; however,
they do not develop secondary sexual characteristics at puberty and do not menstruate.
They have bilateral 'streak gonads,' which typically consist of fibrous tissue and
variable amounts of wavy ovarian stroma. A uterus and fallopian tube are present and
external genitalia are female (reviewed by Berkovitz et al., 1991). - Genetic Heterogeneity
of 46,XY Sex Reversal Male sexual determination is initiated by Y-chromosomal SRY,
which activates a cascade of genes that lead the embryonic gonad to develop into a
testis. Fetal testicular Sertoli cells then produce mullerian inhibitory substance
(600957), which is responsible for the involution of the mullerian ducts, which would
otherwise develop into the uterus, fallopian tubes, and cervix. Fetal testicular Leydig
cells produce testosterone from cholesterol by the sequential action of a series of
enzymes. Subsequent differentiation of male external genitalia also requires the action
of dihydrotestosterone, produced from testicular testosterone. Perturbations in the
enzymes in this classic pathway or in an alternative pathway of testicular androgen
biosynthesis can result in genetic males with disordered sexual development and incompletely
developed ('ambiguous') external genitalia (summary by Fluck et al., 2011). Disorders
of male development for which a genetic cause has been found include 46,XY sex reversal-2
(SRXY2; 300018), which is caused by duplication of the NR0B1 gene (300473) on chromosome
Xp21.3-p21.2; SRXY3 (612965), caused by mutation in the NR5A1 gene (184757) on chromosome
9q33; SRXY4 (154230), caused by deletion on chromosome 9p24.3; SRXY5 (613080), caused
by mutation in the CBX2 gene (602770) on chromosome 17q25; SRXY6 (613762), caused
by mutation in the MAP3K1 gene (600982) on chromosome 5q11.2; SRXY7 (233420), caused
by mutation in the DHH gene (605423) on chromosome 12q13; and SRXY8 (614279), caused
by mutation in the AKR1C2 gene (600450) on chromosome 10p15, with a possible contribution
from the closely linked AKR1C4 gene (600451).;
Inheritance : Y-linked;
Molecular basis : Caused by mutation in the sex-determining region gene (SRY, 480000.0001);
Neoplasia : Gonadoblastoma;
Prefixed ID : #400044;
Origin ID : 400044;
UMLS CUI : C2748896;
Automatic exact mappings (from CISMeF team)
- Currated CISMeF NLP mapping
- DO Cross reference
- Genes related to phenotype
- HPO term(s)
- ORDO concept(s)
- Semantic type(s)
- UMLS correspondences (same concept)
- Validated automatic mappings to NTBT
