To analyze nuclear receptor subfamily 5 group A member 1 (NR5A1) gene mutations in a cohort of Chinese patients with 46, XY Disorders of Sex Development (DSD).
NLRP3, apoptosis-associated speck-like protein containing CARD (ASC), caspase-1, inducible nitric oxide synthase (iNOS) and Arginase (Arg-1) protein expression was detected using western blotting.
Moreover, this decoction inhibited nuclear entry of nuclear factor-kappa B (NF-<i>κ</i>B) with the reduction of phosphorylated protein of NF-<i>κ</i>B (p-NF-<i>κ</i>B) and inhibitor of NF-<i>κ</i>B alpha (p-I<i>κ</i>B<i>α</i>) and downregulated protein of nod-like receptor family pyrin domain-containing 3 (NLRP3), apoptosis-associated speck-like protein containing CARD (ASC), cysteinyl aspartate-specific proteinase-1 (Caspase-1), and IL-1<i>β</i> in liver and brain regions of CUMS rats.
To study the functional properties of six novel missense mutations of the NR5A1 gene encoding the steroidogenic factor 1 (SF-1) identified in six patients with 46,XY disorders of sex development (DSD) and to describe their relative phenotype-genotype relationship.
NLRP3 and ASC-speck protein expression was analyzed by FlowSight AMNIS, whereas production of the pro-inflammatory cytokines IL-1β and IL-18 and of caspase-1 and caspase-8 was measured by ELISA in supernatants.
The purpose of the present study was to investigate whether ten unrelated SRY-negative individuals with this sex differentiation disorder presented a double dose of SOX9 as the cause of their disease.
These enhancers provide a hitherto missing link by which SRY activates SOX9 in humans, and establish SOX9 enhancer mutations as a significant cause of DSD.
Our results suggest that the broad phenotype in these heterozygous NR5A1 46,XY DSD subjects may well be explained by an oligogenic mode of inheritance, in which multiple hits, individually non-deleterious, may contribute to a DSD phenotype unique to each heterozygous SF-1/NR5A1 individual.
A variant in steroidogenic factor-1 (SF-1, encoded by the gene NR5A1), p.Arg92Trp, has recently been reported in multiple families with 46,XX ovotesticular or testicular disorders of sex development (DSD).
The expressions of thioredoxin-interacting protein (TXNIP), nod-like receptor protein 3 (NLRP3), apoptosis-associated speck-like protein containing CARD (ASC), and caspase-1 were assessed by western blot.
Mutations in NR5A1 have been reported as a frequent cause of 46,XY disorders of sex development (DSD) associated to a broad phenotypic spectrum ranging from infertility, ambiguous genitalia, anorchia to gonadal dygenesis and female genitalia.
The differentiation in and/or recruitment to gastrointestinal, lung, and lymphoid tissues of CD11b<sup>+</sup> DCs requires NLRP3, but not apoptosis-associated speck-like protein containing a carboxy-terminal CARD (ASC) or caspase-1, during steady-state and chronic infection.
We aimed to identify the genetic cause in a cohort of 11 unrelated cases and two sisters with 46,XX SRY-negative (ovo)testicular disorders of sex development (DSD).
Of particular interest is a rare XX DSD subtype in which individuals are negative forSRY, the testis determining factor on the Y chromosome, yet develop testes or ovotestes, and both of these phenotypes occur in the same family.
Our study showed that the identified copy number variation region located upstream of the SOX9 gene contains potential regulatory sequences (long non-coding RNA and hfMAGI2) and led to the assumption that a multiplication of this element may alter expression of the SOX9 gene, triggering the DSD phenotype.
Many of the genes mutated in DSD encode transcription factors such as SRY, SOX9, NR5A1, and FOXL2, characterized by a strictly regulated spatiotemporal expression.
The study was limited by inclusion of only members of AIS-DSDSG, a convenience sample where complete AIS is over-represented, and whose views may not represent the opinion of all individuals with DSD conditions.
Our previous work involving the genomic analysis of isolated DSD patients revealed a 78kb minimal sex determining region (RevSex) far upstream of SOX9 that was duplicated in 46,XX and deleted in 46,XY DSDs.