RÉSUMÉ
Testicular disorder of sex development (TDSD) is a rare condition, characterised by a female karyotype, male phenotype, small testes and cryptorchidism. Only a few studies have investigated the genetic causes of male sex reversal. This is the clinical report of an Iranian 46,XX patient presented with TDSD and associated with hypospadias. Whole-exome sequencing (WES) of the patient ascertained the heterozygous missense variant (c.274C>T) in the NR5A1 gene, resulting in a substitution of arginine with tryptophan. The arginine 92 residue was located in a highly conserved region of steroidogenic factor 1 (SF1), which is crucial for its interaction with DNA. Our finding is in line with previous reports, which highlighted the role of p.(Arg92Trp) variant in TDSD individuals. As far as we are aware, this is the first report of TDSD with p.(Arg92Trp) variant in the Iranian population.
Sujet(s)
Syndrome du mâle XX/génétique , Facteur stéroïdogène-1/génétique , Syndrome du mâle XX/sang , Syndrome du mâle XX/complications , Adulte , Atrophie , Azoospermie/étiologie , Hormone folliculostimulante/sang , Hétérozygote , Humains , Hypospadias/complications , Iran , Caryotype , Hormone lutéinisante/sang , Mâle , Mutation faux-sens , Analyse du sperme , Testicule/anatomopathologie , Testostérone/sang , Exome SequencingRÉSUMÉ
BACKGROUND: Sex reversal syndrome (SRS) is a human chromosomal abnormality disease with gender dysplasia, which is characterized by inconsistency between social sexuality and genetic sexuality. METHODS: We report a case of sex reversal syndrome with 46, XX. Chemiluminescence was used to detect serum sex hormones, including testosterone (T), luteinizing hormone (LH), and follicular stimulation (FSH), and 15 karyotype analysis. RESULTS: The levels of FSH and LH in serum were high, and the level of T in serum was low. The karyotype analysis showed that the nuclear type of the patient was 46, XX. The examination of the sex-determining region Y (SRY) gene showed positive results. CONCLUSIONS: The main principle of diagnosing the 46, XX male SRS is early determination of chromosome, gonad, and genitalia gender. When the prenatal ultrasound diagnosis of pregnant women is inconsistent with the results of cytogenetics, caution should be taken to avoid the birth of children with 46, XX male SRS.
Sujet(s)
Syndrome du mâle XX/génétique , Gène sry/génétique , Aberrations des chromosomes sexuels , Syndrome du mâle XX/sang , Adulte , Hormone folliculostimulante/sang , Humains , Infertilité masculine/génétique , Hormone lutéinisante/sang , Mâle , Testostérone/sangRÉSUMÉ
ABSTRACT Objective To present clinical, chromosomal and hormonal features of ten cases with SRY-positive 46,XX testicular disorder of sex development who were admitted to our infertility clinic. Cases and Methods Records of the cases who were admitted to our infertility clinic between 2004 and 2015 were investigated. Ten 46,XX testicular disorder of sex development cases were detected. Clinical, hormonal and chromosomal assessments were analized. Results Mean age at diagnosis was 30.4, mean body height was 166.9cm. Hormonal data indicated that the patients had a higher FSH, LH levels, lower TT level and normal E2, PRL levels. Karyotype analysis of all patients confirmed 46,XX karyotype, and FISH analysis showed that SRY gene was positive and translocated to Xp. The AZFa, AZFb and AZFc regions were absent in 8 cases. In one case AZFb and AZFc incomplete deletion and normal AZFa region was present. In the other one all AZF regions were present. Conclusion Gonadal development disorders such as SRY-positive 46,XX testicular disorder of sex development can be diagnosed in infertility clinics during infertility work-up. Although these cases had no chance of bearing a child, they should be protected from negative effects of testosterone deficiency by replacement therapies.
Sujet(s)
Humains , Mâle , Adulte , Syndrome du mâle XX/génétique , Infertilité masculine/génétique , Études rétrospectives , Syndrome du mâle XX/sang , Caryotype , Infertilité masculine/sangRÉSUMÉ
OBJECTIVE: To present clinical, chromosomal and hormonal features of ten cases with SRY-positive 46,XX testicular disorder of sex development who were admitted to our infertility clinic. CASES AND METHODS: Records of the cases who were admitted to our infertility clinic between 2004 and 2015 were investigated. Ten 46,XX testicular disorder of sex development cases were detected. Clinical, hormonal and chromosomal assessments were analized. RESULTS: Mean age at diagnosis was 30.4, mean body height was 166.9cm. Hormonal data indicated that the patients had a higher FSH, LH levels, lower TT level and normal E2, PRL levels. Karyotype analysis of all patients confirmed 46,XX karyotype, and FISH analysis showed that SRY gene was positive and translocated to Xp. The AZFa, AZFb and AZFc regions were absent in 8 cases. In one case AZFb and AZFc incomplete deletion and normal AZFa region was present. In the other one all AZF regions were present. CONCLUSION: Gonadal development disorders such as SRY-positive 46,XX testicular disorder of sex development can be diagnosed in infertility clinics during infertility workup. Although these cases had no chance of bearing a child, they should be protected from negative effects of testosterone deficiency by replacement therapies.
Sujet(s)
Syndrome du mâle XX/génétique , Infertilité masculine/génétique , Syndrome du mâle XX/sang , Adulte , Humains , Infertilité masculine/sang , Caryotype , Mâle , Études rétrospectivesSujet(s)
Duplication de gène/génétique , Troubles ovotesticulaires du développement sexuel/génétique , Facteurs de transcription SOX-B1/génétique , Protéine de la région déterminant le sexe du chromosome Y , Syndrome du mâle XX/sang , Syndrome du mâle XX/génétique , Syndrome du mâle XX/anatomopathologie , Enfant d'âge préscolaire , Cryptorchidie/génétique , Cryptorchidie/anatomopathologie , Humains , Hypospadias/génétique , Mâle , Troubles ovotesticulaires du développement sexuel/sang , Troubles ovotesticulaires du développement sexuel/anatomopathologieRÉSUMÉ
The XX male syndrome - Testicular Disorder of Sexual Differentiation (DSD) is a rare condition characterized by a spectrum of clinical presentations, ranging from ambiguous to normal male genitalia. We report hormonal, molecular and cytogenetic evaluations of a boy presenting with this syndrome. Examination of the genitalia at age of 16 months, showed: penis of 3.5 cm, proximal hypospadia and scrotal testes. Pelvic ultrasound did not demonstrate Mullerian duct structures. Karyotype was 46,XX. Gonadotrophin stimulation test yielded insufficient testosterone production. Gonadal biopsy showed seminiferous tubules without evidence of Leydig cells. Molecular studies revealed that SRY and TSPY genes and also DYZ3 sequences were absent. In addition, the lack of deletions or duplications of SOX9, NR5A1, WNT4 and NROB1 regions was verified. The infant was heterozygous for all microsatellites at the 9p region, including DMRT1 gene, investigated. Only 10% of the patients are SRY-negative and usually they have ambiguous genitalia, as the aforementioned patient. The incomplete masculinization suggests gain of function mutation in one or more genes downstream to SRY gene.