SRY Gene Research Articles

Swyer’s Syndrome: Discordance between Genetic and Biological Sex - Case report

Swyer’s syndrome is a rare condition in which a disorder of the sex chromosomes produces a defective gonadogenesis with total absence of functional gonadal tissue, resulting in pure gonadal dysgenesis and discordance between genetic and biological sex. The gonads appear as rudimentary bands and the risk of developing gonadal tumors is significant. The etiology is not clear: one of the possible causes is the absence or mutations of the SRY gene located on the Y chromosome. This gene is considered to be the most important, although it is known that there are other genes involved in the cascade of sexual differentiation. This article reports the case of a 17-year-old female phenotype patient who was studied for primary amenorrhea and presented laboratory findings compatible with hypergonadotropic hypogonadism, 46XY karyotype, who was diagnosed with Swyer Syndrome.

Application of low-depth whole genome sequencing for copy number variation analysis in children with disorders of sex development

To assess the value of copy number variation sequencing (CNV-seq) for the diagnosis of children with disorders of sex development (DSD). Five children with DSD who presented at the First Affiliated Hospital of Zhengzhou University from October 2019 to October 2020 were enrolled. In addition to chromosomal karyotyping, whole exome sequencing (WES), SRY gene testing, and CNV-seq were also carried out. Child 1 and 2 had a social gender of female, whilst their karyotypes were both 46,XY. No pathogenic variant was identified by WES. The results of CNV-seq were 46,XY,+Y (1.4) and 46,XY,-Y (0.75), respectively. The remaining three children have all carried an abnormal chromosome Y. Based on the results of CNV-seq, their karyotypes were respectively verified as 45,X[60]/46,X,del(Y)(q11.221)[40], 45,X,16qh+[76]/46,X,del(Y)(q11.222),16qh+[24], and 45,X[75]/46,XY[25]. CNV-seq may be used to verify the CNVs on the Y chromosome among children with DSD and identify the abnormal chromosome in those with 45,X/46,XY. Above results have provided a basis for the clinical diagnosis and treatment of such children.

Genetic Monitoring of the Last Captive Population of Greater Mouse-Deer on the Thai Mainland and Prediction of Habitat Suitability before Reintroduction

Developing successful conservation programs for genetically depleted species is challenging. Survival and adaptive potential are related to genetic and habitat factors; therefore, conservation programs are designed to minimize risks associated with inbreeding and loss of genetic diversity. The greater mouse-deer (Tragulus napu) is a true forest species that contributes to seed distribution dynamics in forests. However, with continuous demographic decline over the last century in the wild, only captive populations of the greater mouse-deer remain on the Thai mainland. A restoration program initiated 20 years ago has increased their population to more than 100 individuals but maintaining high genetic diversity in a small captive population is crucial for successful recovery. Microsatellite genotyping and mitochondrial D-loop and SRY gene sequence analyses were performed to examine the genetic diversity and population structure in 123 greater mouse-deer (64 females and 59 males). Highly reduced effective captive population size with trends of inbreeding were observed. No historical bottleneck was observed. These conditions have reduced their reproductive fitness and ability to adapt to environmental change, increasing the risk of population decline and eventual extinction. Demographic analyses suggested a recent captive population expansion due to effective animal welfare and reproduction. The results also suggested that population size at equilibrium is the main factor of allelic diversity (number of alleles). Large habitat carrying capacity, representing each fixed captive population size can support the genetic diversity of greater mouse-deer. We also identified suitable habitat areas for reintroduction and long-term in situ conservation of greater mouse-deer using maximum entropy modeling. Based on the environmental variables, species distribution modeling for greater mouse-deer indicated lowland tropical forest regions in the Khlong Saeng-Khao Sok forest complexes as most suitable and requiring urgent habitat improvement. These findings highlight the relevance of careful genetic monitoring and habitat suitability for the long-term conservation of greater mouse-deer and enhance the success of future conservation plans.

Mutation analysis of WNT4 gene in SRY negative 46,XX DSD patients with Mullerian agenesis and/or gonadal dysgenesis- An Indian study

Developmental disruption of the Mullerian duct and gonads in females leads to Mullerian agenesis and gonadal dysgenesis, respectively. These two structural abnormalities are coming under the 46,XX DSD (Disorders of Sexual Development) classification, the majority of cases the aetiology remains elusive. Without the SRY gene, WNT4 plays a key role in female reproductive structure development. Since there are no studies that explored the involvement of the WNT4 gene in Indian 46,XX DSD patients, we analysed the role of WNT4 in Indian 46,XX DSD patients with Mullerian agenesis and/or Gonadal dysgenesis. In our study, we recruited 103 adolescent girls with primary amenorrhea. After the cytogenetic and SRY gene analysis, we included thirty-two 46,XX DSD patients with Mullerian agenesis and/or gonadal dysgenesis for WNT4 gene mutation analysis. PCR sequencing was performed for all the coding exons of the WNT4 gene. Bioinformatic tools like Mutation Taster, Human Splicing Finder, and miRDB were used. We observed single nucleotide variations in three patients. One patient showed a known synonymous polymorphism (c.861C > T; p.G287G, rs544988174). miRDB data revealed the absence of microRNA regulatory sites in this region. The other two cases carried a nucleotide substitution in intronic regions and did not affect the normal splicing mechanism. In conclusion, we could not find any indication about WNT4 involvement in the disease condition. In the future, WNT4 promoter analysis in these patients and molecular characterization of the WNT4 coding and promoter region in more patients are needed to link WNT4 variants with these structural abnormalities.

English

Disorders of sex development (DSD) when diagnosed early is important as it pose a real public health problem in Senegal. Among the supporting tools, molecular ones, which are not available everywhere are very useful. In this context, cytogenetic and molecular analyses were implemented in cytology laboratory at the Aristide Le Dantec hospital to enhance the DSDs diagnosis as well as evaluate the impact of the parents' age on such abnormalities. 55 cases of DSD have been received in the cytology laboratory for which cytogenetic (Barr chromatin and GTG karyotype) and molecular (SRY gene research) techniques have been used to characterize these anomalies according to the standards described in the international nomenclature. Three categories of DSD were found, namely 46,XX DSD, 46,XY DSD and chromosomal DSD. SRY is present in 4 patients 46,XX and absent in 3 patients 46,XY and results showed that the diagnosis is made earlier than previously (about 07 years). The study thus suggests the importance of complementarity (cytogenetics and molecular biology) in the diagnosis of DSD but also and especially the importance of early diagnosis from birth. Analysis of the epidemiological data also showed a slight correlation between maternal age and DSD. This showed us that a better characterization of DSD via increasingly powerful tools helps understanding on such pathologies and allows good medical care for patients.   Key words: Disorders of sex development (DSD), karyotype, SRY, hermaphroditis.

Preventing Female Virilisation: Role of Antenatal Dexamethasone

Antenatal treatment with dexamethasone in pregnancies affected by congenital adrenal hyperplasias (CAH) therefore suppresses fetal androgen production and prevents virilisation of female infants. Antenatal DXM is reported to be efficacious, preventing or ameliorating virilisation in 80–85% of cases. Materials and methods: In this study, we report a case of patient pregnant at 6 weeks; with a history of 2 children followed up for a classic form of HCS, she is admitted to our department for the administration of dexamethasone to prevent fetal virilization. Case Report: 23-year-old patient pregnant at 6 weeks, not known of having congenital adrenal hyperplasia (CAH), concept of consanguineous marriage 1 degree; she had a history of 2 children followed up for a classic form of HCS, the first died at the age of 1 and 10 months and the 2 child died on D26 of life. After having made a prenatal diagnosis where an analysis of the SRY gene on fetal circulating DNA showed the absence of this gene, which confirms the female sex of the fetus. An obstetrical ultrasound was done which objectified a pregnancy estimated at 6 weeks with suspicion of clitoral hypertrophy (At 16 weeks), in view of this observation the patient was referred to us for additional care and possible dexametasone. On questioning, the patient did not report any signs of hyperandrogenism. All evolving in a context of unquantified moderate weight loss and asthenia without signs of adrenal insufficiency. The clinical examination showed no melanoderma or slate spots, BP= 105/71mmHg, RR = 19 cycles/min. CF=81bpm? BMI = 28.68 kg/m2. Tanner: S5P5. the patient was put on 1.5 mg/d of dexamethasone divided into 3 doses.a monthly measurement of DHEAS and cortisol was requested. The Decrease of plasma concentrations of cortisol and DHEAS in the mother testifies to good fetal adrenal suppression. A low-calorie diet and monitoring of blood pressure and blood sugar to detect signs of under or overdose of corticosteroid .....

Yolk sac tumor and dysgerminoma in the left gonad following gonadoblastoma in the right gonad in a 46,XY DSD with a novel SRY missense mutation: a case report

BackgroundApproximately 10–15% of 46,XY disorders of sex development (DSDs) have an SRY mutation residing in the high mobility group (HMG) domain. Here, we present a case of 46,XY DSD caused by a novel missense mutation in the HMG region of SRY rapidly progressing to germ cell tumors (GCTs).Case presentationAn adolescent female (15 years old) exhibiting primary amenorrhea was later diagnosed as a 46,XY female with bilateral gonadal dysplasia on the basis of peripheral lymphocyte karyotype 46,XY and a novel missense mutation in SRY (c.281 T > G, p.L94R). The novel missense mutation (c.281 T > G, p.L94R) and its adjacent region were conserved. Protein structure analysis showed that the mutant site was located in the middle of the HMG domain, and the mutant protein had a diminished ability to bind to DNA. Imaging examination revealed an adolescent female with a naive uterus. Laparoscopy and initial pathological examination revealed left gonadal dysplasia and right gonadal dysplasia with gonadoblastoma (GB). Right gonadectomy by laparoscopy was performed upon consent from the patient’s parents. Less than 1 year postoperatively, the left gonadal gland deteriorated as observed by the findings of a mass in the left adnexal region by pelvic MRI and serum AFP > 1000 ng/ml by serological tests, and then total hysterectomy and adnexal and left gonadectomy by laparoscopy were performed. The GCT stage was classified as stage Ic according to FIGO. At this time, pathologic examination showed that the left gonad had progressed to yolk sac tumor and dysgerminoma. The patient underwent chemotherapy post-operatively but developed type III myelosuppression and tumor recurrence several months later.ConclusionsThe patient initially presented with right gonadoblastoma but chose only right gonadectomy by laparoscopy to preserve the female sex characteristics, which resulted in rapid deterioration of the left gonad and poor treatment outcomes. This case demonstrates the importance of early genetic diagnosis and treatment of 46,XY female DSD.

Additional evidence for the role of chromosomal imbalances and SOX8, ZNRF3 and HHAT gene variants in early human testis development

BackgroundForty-six ,XY Differences/Disorders of Sex Development (DSD) are characterized by a broad phenotypic spectrum ranging from typical female to male with undervirilized external genitalia, or more rarely testicular regression with a typical male phenotype. Despite progress in the genetic diagnosis of DSD, most 46,XY DSD cases remain idiopathic.MethodsTo determine the genetic causes of 46,XY DSD, we studied 165 patients of Tunisian ancestry, who presented a wide range of DSD phenotypes. Karyotyping, candidate gene sequencing, and whole-exome sequencing (WES) were performed.ResultsCytogenetic abnormalities, including a high frequency of sex chromosomal anomalies (85.4%), explained the phenotype in 30.9% (51/165) of the cohort. Sanger sequencing of candidate genes identified a novel pathogenic variant in the SRY gene in a patient with 46,XY gonadal dysgenesis. An exome screen of a sub-group of 44 patients with 46,XY DSD revealed pathogenic or likely pathogenic variants in 38.6% (17/44) of patients.ConclusionRare or novel pathogenic variants were identified in the AR, SRD5A2, ZNRF3, SOX8, SOX9 and HHAT genes. Overall our data indicate a genetic diagnosis rate of 41.2% (68/165) in the group of 46,XY DSD.

Sifrim-Hitz-Weiss/CHD4-related syndrome: A new case report.

Sifrim-Hitz-Weiss/CHD4-related syndrome: A new case report.

Concerns over the declining human Y-chromosome and social functioning

In humans, like other mammals, females have two X chromosomes and males have one X and one Y chromosome. The Y chromosome contains a sex-determining gene SRY that kick-starts male development in the embryo and activates other genes that regulate the testicular development. Researchers have found that the Y chromosome seems to be disappearing, as seen in many other mammals, including rodents. The male eastern Europe vole and the spiny rats of Japan have completely lost their Y chromosomes and the Sry gene. However, the SOX9 protein plays a key role there in determining their sex. The new finding so support the possibility that humans too, may evolve a new sex determining mechanism. The sex chromosome genes act within cells to cause differences in phenotypes of XX and XY cells throughout the body. In the gonad, they determine the type of gonad, leading to differences in secretion of testicular vs. ovarian hormones, which cause further sex differences in tissue function. The human brains, as shown by neuroimaging, demonstrate variation in different areas of the brain that are associated with both differences in gonadal hormones, and in the number of X and Y chromosomes. In humans, males and females are different because of innate biological differences, and also they have different social and physical environments. Biologists tend to emphasize the importance of biological variables, and sociologists tend to emphasize the role of gendered environments. The Sry and the other Y-linked genes not only determine the differences in gonad development, they are also linked to maintaining gender balance (biologically) and various functions in the brain, including appropriate social responses by supporting behavioral flexibility, attention and emotion. In this article, we have reviewed the function of the Y chromosome and the Sry gene and their possible alternatives in case of their future extinction.

Primer infertil erkeklerdeki Y-kromozom mikrodelesyon sıklığı

OBJECTIVES: There are SRY (sex-determining region Y) region, which plays a role in testicular development, and genes related to spermatogenesis on the Y chromosome. Its long arm contains the azoospermia factor (AZF) region (AZFa, AZFb, and AZFc subregions). Microdeletions in this region are responsible for azoospermia and oligospermia and cause male infertility. The aim of this study was to analyze the incidence of microdeletion in the AZF region of the Y chromosome in male patients with primary infertility with azoospermia and oligospermia. MATERIAL and METHODS: A total of 206 male patients were analyzed between December 2020 and December 2022. The diagnosis of azoospermia and oligospermia was made based on semen analysis. Patients with normal karyotype were included in the study. For the definitive diagnosis of microdeletions in the AZF region, 20 different sequence tagged sites (STS) were used, including the recommendation of the European Academy of Andrology (EAA) and the European Molecular Genetics Quality Network (EMQN). Each region was amplified by polymerase chain reaction (PCR) method and analyzed by fragment method in ABI 3500 DNA Sequence instrument. RESULTS: Microdeletion was detected in the AZF region of the Y chromosome in 17 of 206 patients (8%, 3) with normal karyotype. With the study, we identified the deletions of each subregion of AZF in our population. The presence of microdeletions in the AZFc region was most common. b2/b4 complete AZF/c microdeletions were higher than the g/gr partial AZF/c deletion. CONCLUSION: The study confirmed that the incidence of microdeletion of AZF subregions in primary infertile male patients was 8%,3 and was prognostically significant. The frequency of Y chromosome microdeletion was found to be consistent with the literature. Keywords: AZF region, azoospermia, oligospermia, primary male infertility, Y-chromosome microdeletion

Phylogenetic Relationship and Molecular Divergence Dating Using SRY Gene Polymorphism about Four Ladoum Sheep Lineages in Senegal

Animal genetic resources are playing a vital role in livestock production and are essential to food security. The present study aims to contribute to a better understanding genetic local sheep breeds and to elucidate the phylogenetic relationships through the evolution of the SRY gene in four different lineages of Ladoum sheep raised in Senegal. After a brief analysis of genetic diversity, the phylogenetic relationships and molecular dating were inferred through haplotype networks and four phylogenetic reconstruction methods. The different haplotype networks are constructed with NETWORK ver. 5.0.0.0 using the Median-Joining method. Phylogenetic trees were reconstructed using neighbor-joining, maximum parsimony, maximum likelihood and Bayesian inference. The robustness of the nodes in phylogenetic trees of the three first methods was assessed by 1000 bootstraps. For Bayesian inference, the posterior probability distribution of the trees was estimated by 4 MCMC chains. 5,000,000 generations were performed for each of the chains by sampling the different parameters every 1000 generations. Results show a low polymorphism. Haplotypic diversity is much higher than the average nucleotide divergence between all pairs of haplotypes. The majority and central haplotype indicates a close relationship between “Batling” and “Tyson” individuals. “Birahim” lineage is very distinct from the rest. Phylogenetic trees confirm two genetically separate clades between “Birahim” and the other lineages. The period of divergence between “Birahim” lineage versus the common ancestor of the other three lineages was 2504 years ago. The polyphyly revealed in “Birahim” lindicates that this lineage does not contain the common ancestor of all individuals who compose it. It could therefore be derived from two or more sheep breeds with a common ancestor, Ovis aries. The monophyletic clade appears to be a group including a common ancestor and all of its genetic descendants. This group, bringing together the other three lineages, is in the process of being structured into sub-lineages. This study is the first to show that there are only two genetic lines within ladoum sheep in Senegal.

Genetic analysis of Turner syndrome in Tunisian patients

Background/aim Turner syndrome (TS) is a rare sex chromosome abnormality in women, occurring in approximately one in 2500 live births, associated with a wide range of clinical stigmata of which short stature, ovarian dysgenesis, and dysmorphic features are the most frequent. Morbidity and mortality are clearly increased compared with the general population, and the average age at diagnosis is quite delayed. Even if the majority of females with TS have a non-mosaic 45,X karyotype, several karyotype variations exist, including short or long arm deletion, ring X isochromosome of the long arm, and 45,X 46,XX mosaicism. This explains the large phenotypic and genetic heterogeneities of TS, which make the diagnosis and especially the management increasingly difficult. We present in this work a genetic study of TS in the Tunisian population to establish a genotype–phenotype correlation, which would be of great help for the diagnosis and the care of patients. Patients and methods A total of 26 unrelated Tunisian girls were included in this study. All patients underwent a complete clinical and biochemical examination as well as karyotyping. The screening for the SRY gene was carried out by fluorescence in-situ hybridization or by PCR. Results Cytogenetic results showed a prevalence of the 45,X karyotype in 46% of patients and various proportions of the other karyotypes. However, genotype–phenotype correlation revealed several discrepancies regarding the major signs and the age at diagnosis. The comparison of the approaches used for the screening of the SRY gene showed that karyotyping is unable to detect low 45,X/46,XY mosaicism and that it is the PCR that would be able to do, eliciting its role to make a reliable diagnosis. Conclusion The karyotype alone is not sufficient to make a TS diagnosis in cases of weak mosaicism, and the great heterogeneity that reigns the syndrome elicits an epigenetic and transcriptomic exploration of several genes that recently seem to be involved in the disease.

SRY Gene Based Kinship Relationship of Limousin and Madrasin Cattle

SRY Gene Based Kinship Relationship of Limousin and Madrasin Cattle

Application of the PCR and allele-specific PCR-nucleic acid lateral flow immunoassay for the detection of the SRY gene and the G1138A mutation in the FGFR3 gene for the human DNA

Application of the PCR and allele-specific PCR-nucleic acid lateral flow immunoassay for the detection of the SRY gene and the G1138A mutation in the FGFR3 gene for the human DNA

Gut microbiota-derived short-chain fatty acids regulate group 3 innate lymphoid cells in HCC.

Type 3 innate lymphoid cells (ILC3s) are essential for host defense against infection and tissue homeostasis. However, their role in the development of HCC has not been adequately confirmed. In this study, we investigated the immunomodulatory role of short-chain fatty acids (SCFAs) derived from intestinal microbiota in ILC3 regulation. We report that Lactobacillus reuteri was markedly reduced in the gut microbiota of mice with HCC, accompanied by decreased SCFA levels, especially acetate. Additionally, transplantation of fecal bacteria from wild-type mice or L. reuteri could promote an anticancer effect, elevate acetate levels, and reduce IL-17A secretion in mice with HCC. Mechanistically, acetate reduced the production of IL-17A in hepatic ILC3s by inhibiting histone deacetylase activity, increasing the acetylation of SRY (sex-determining region Y)-box transcription factor 13 (Sox13) at site K30, and decreasing expression of Sox13. Moreover, the combination of acetate with programmed death 1/programmed death ligand 1 blockade significantly enhanced antitumor immunity. Consistently, tumor-infiltrating ILC3s correlated with negative prognosis in patients with HCC, which could be functionally mediated by acetate. These findings suggested that modifying bacteria, changing SCFAs, reducing IL-17A-producing ILC3 infiltration, and combining with immune checkpoint inhibitors will contribute to the clinical treatment of HCC.

Discovery of the human homolog of sex-determining region (SRY) gene in dioecious plants

Sex determination in the early developmental stages of dioecious crops is economically-beneficial. During this study, a human homology of SRY gene was successfully identified in dioecious crops. SRY gene sequences of date palm and jojoba were submitted to GenBank under the accession numbers KC577225 and MK991776, respectively. This is the first report regarding the novel sex-determination methodology of four dioecious plants (jojoba, date palm, papaya, and pistachios). SRY sex gene was found in all the tested dioecious plant and human samples. This novel approach is simple and of significant importance for breeders. It facilitates the unambiguous selection of jojoba and date palm female plants at an early age and reduces the plantation cost of cultivating non-productive male plants. This is a rapid sex-determination technique for dioecious plants and mammals at an early stage. This technique specifically targets the SRY sequence that has been comprehensively investigated in humans. The kit development for the SRY-based sex determination of various crops is in progress.

GENETIC VARIATION AND PHYLOGENETIC RELATIONSHIPS BASED ON TESTIS DETERMINING REGION-Y (SRY) GENE IN THE LAKOR GOAT BREED

Lakor goat is an Indonesian indigenous goat breeds that successfully survive and is adaptive in the ecology of Lakor island in Southwest Maluku with high temperatures and curah limited rainfall. Genetic variations in Y-chromosome enable researchers to identify paternal lineages, which are informative for introgressions and migrations. This study aims to characterize genetic variation and phylogenetic relationships of Lakor goats based on male-specific region markers, i.e., sex-determining region-Y (SRY) gene. The genomes of 84 follicle samples of male goats (bucks) collected from Lakor island, were analyzed. The amplified product for SRY was 850 bp in encoding region (exon-1). Genetic variation and paternal phylogenetic relationship were established following sequencing using MEGA version X.0 software. The results of Y-chromosome alignments of the entire sequences identified two polymorphic nucleotides between individual goats within the population. Two polymorphism nucleotides, i.e. site 362 (A-G), and found in LK3, LK7, LK11, and LK13 samples, while site 410 (C-T) was found in LK3, LK7, LK11, LK13, and LK24 samples. The two mutations are categorized as substitution (transition type) and this is in the exon-1 area. This study concluded that genetic variation is very low in the Lakor goat breed and phylogenetic analysis grouping is a single clade or monophyletic group.

Characterisation of eight cattle with Swyer syndrome by whole-genome sequencing.

Swyer syndrome is where an individual has the karyotype of a typical male yet is phenotypically a female. The lack of a (functional) SRY gene located on the Y-chromosome is implicated in some cases of the Swyer syndrome, although many Swyer individuals with an apparently fully functional SRY gene have also been documented. The present study undertook whole genome sequence analyses of eight cattle with suspected Swyer syndrome and compared their genome to that of both a control male and female. Sequence analyses coupled with female phenotypes confirmed that all eight individuals had the 60,XY sex reversal Swyer syndrome. Seven of the eight Swyer syndrome individuals had a deletion on the Y chromosome encompassing the SRY gene (i.e., SRY-). The eighth individual had no obvious mutation in the SRY gene (SRY+) or indeed in any reported gene associated with sex reversal in mammals; a necropsy was performed on this individual. No testicles were detected during the necropsy. Histological examination of the reproductive tract revealed an immature uterine body and horns with inactive glandular tissue of normal histological appearance; both gonads were elongated, a characteristic of most reported cases of Swyer in mammals. The flanking sequence of 11 single nucleotide polymorphisms within 10 kb of the SRY gene are provided to help diagnose some cases of Swyer syndrome. These single nucleotide polymorphisms will not, however, detect all cases of Swyer syndrome since, as evidenced from the present study (and other studies), some individuals with the Swyer condition still contain the SRY gene (i.e., SRY+).

Challenges in the Diagnosis of XY Differences of Sexual Development

Background: We report the clinical case of female patient with 46,XY difference of sexual development (DSD) and discuss the challenges in the differential diagnosis between complete gonadal dysgenesis (also called Swyer syndrome) and complete androgen insensitivity syndrome. Case Presentation: The patient's with primary amenorrhea gynaecological examination and magnetic resonance imaging (MRI) revealed the absence of the uterus and a very short vagina. Two sclerotic structures, similar to ovaries, were recognised bilaterally in the iliac regions. Hormonal assay tests revealed hypergonadotropic hypogonadism and the testosterone level was above normal. The karyotype was 46,XY and a diagnosis of Swyer syndrome was made. At the age of 41, the patient underwent a gynaecological review and after evaluating her tests and medical history, the previous diagnosis was questioned. Therefore, a molecular analysis of sex-determining region Y (SRY) and androgen receptor (AR) genes was made and the results instead led to a definite diagnosis of complete androgen insensitivity syndrome. Conclusions: The presented case illustrates that differentiating between complete gonadal dysgenesis and complete androgen insensitivity can be challenging. A well-established diagnosis is crucial because the risk of malignancy is different in those two syndromes, as well as the timing and importance of gonadectomy.