Screening for mutations in the SRY gene in patients with mixed gonadal dysgenesis or with Turner syndrome and Y mosaicism

Canto, Patricia; Galicia, Norma; Söderlund, Daniela; Escudero, Irineo; Méndez, Juan Pablo

doi:10.1016/j.ejogrb.2003.10.035

Cited by 15 publications

(10 citation statements)

References 18 publications

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“…Our results suggest that mutations in the SRY are rarely identified in patients with mosaicisms of the Y chromosome, similarly to previous descriptions [12,23,24,27], weakening the putative association of point mutations in SRY to compromised Y chromosome integri- ty. Therefore, a significant role of mutated SRY in the etiology of gonadal dysgenesis in patients harboring 45,X/46,XY karyotype and variants seems very unlikely.…”

Section: Discussionsupporting

confidence: 70%

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The Role of <i>SRY</i> Mutations in the Etiology of Gonadal Dysgenesis in Patients with 45,X/46,XY Disorder of Sex Development and Variants

Nishi¹,

Costa²,

Oliveira³

et al. 2010

Horm Res Paediatr

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Background: The potential involvement of SRY in abnormal gonadal development in 45,X/46,X,der(Y) patients was proposed following the identification of SRY mutations in a few patients with Turner syndrome (TS). However, its exact etiological role in gonadal dysgenesis in patients with Y chromosome mosaicisms has not yet been clarified. Aims: It was the aim of this study to screen for allelic variation in SRY in a large cohort of patients with disorders of sex development due to chromosomal abnormalities with 45,X/46,X,der(Y) karyotype. Patients: Twenty-seven patients, 14 with TS and 13 with mixed gonadal dysgenesis (MGD), harboring 45,X/46,X,der(Y) karyotypes were selected. Methods: Genomic DNA was extracted from peripheral blood leukocytes of all patients and from gonadal tissue in 4 cases. The SRY coding region was PCR amplified and sequenced. Results: We identified only 1 polymorphism (c.561C→T) in a 45,X/46,XY MGD patient, which was detected in blood and in gonadal tissue. Conclusion: Our results indicate that mutations in SRY are rare findings in patients with Y chromosome mosaicisms. Therefore, a significant role of mutated SRY in the etiology of gonadal dysgenesis in patients harboring 45,X/46,XY karyotype and variants seems very unlikely.

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Section: Discussionsupporting

confidence: 70%

“…Unlike TS, no SRY mutation has been identified in patients with MGD until now [23,24]. Canto et al [25], analyzing the desert hedgehog (DHH) gene in patients with MGD, described a mutation c.1086delG in 2 of 10 individuals, in heterozygous state.…”

Section: Discussionmentioning

confidence: 99%

The Role of <i>SRY</i> Mutations in the Etiology of Gonadal Dysgenesis in Patients with 45,X/46,XY Disorder of Sex Development and Variants

Nishi¹,

Costa²,

Oliveira³

et al. 2010

Horm Res Paediatr

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“…The proportion of the 45,X cell line in various tissues especially the gonads [Alvarez‐Nava et al, 2003; DesGroseillier et al, 2006]. Other associated factors are mutations affecting the SRY gene leading to functional loss [Canto et al, 2000; Fernandez et al, 2002] or mutations affecting other genes involved in the testis determination pathway [Morava et al, 2000; Alvarez‐Nava et al, 2001, 2003; Canto et al, 2004]. …”

Section: Introductionmentioning

confidence: 99%

Isodicentric Y chromosomes in Egyptian patients with disorders of sex development (DSD)

Mekkawy

Kamel

El-Ruby

et al. 2012

American J of Med Genetics Pt A

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Isodicentric chromosome formation is the most common structural abnormality of the Y chromosome. As dicentrics are mitotically unstable, they are subsequently lost during cell division resulting in mosaicism with a 45,X cell line. We report on six patients with variable signs of disorders of sex development (DSD) including ambiguous genitalia, short stature, primary amenorrhea, and male infertility with azoospermia. Cytogenetic studies showed the presence of a sex chromosome marker in all patients; associated with a 45,X cell line in five of them. Fluorescence in situ hybridization (FISH) technique was used to determine the structure and the breakage sites of the markers that all proved to be isodicentric Y chromosomes. Three patients, were found to have similar breakpoints: idic Y(qter→ p11.32:: p11.32→ qter), two of them presented with ambiguous genitalia and were found to have ovotesticular DSD, while the third presented with short stature and hypomelanosis of Ito. One female patient presenting with primary amenorrhea, Turner manifestations and ambiguous genitalia revealed the breakpoint: idic Y (pter→q11.1::q11.1→pter). The same breakpoint was detected in a male with azoospermia but in non-mosaic form. An infant with ambiguous genitalia and mixed gonadal dysgenesis (MGD) had the breakpoint at Yq11.2: idic Y(pter→q11.2::q11.2→pter). SRY signals were detected in all patients. Sequencing of the SRY gene was carried out for three patients with normal results. This study emphasizes the importance of FISH analysis in the diagnosis of patients with DSD as well as the establishment of the relationship between phenotype and karyotype.

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“…Other associated factors such as mutations affecting the SRY gene or other genes involved in the testis-determining pathway could not be excluded in such cases [Fernandez et al, 2002;Alvarez-Nava et al, 2003;Canto et al, 2004]. Patient 3 exhibited an idic(Yq) abnormality in 36% of blood lymphocytes, associated with a 45,X cell line.…”

Section: Discussionmentioning

confidence: 99%

Sex Chromosome Mosaicism in the Gonads of DSD Patients: A Karyotype/Phenotype Correlation

Kamel

El-Ghany²,

Mekkawy³

et al. 2015

Sex Dev

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Sex chromosome mosaicism results in a large clinical spectrum of disorders of sexual development (DSD). The percentage of 45,X cells in the developing gonad plays a major role in sex determination. However, few reports on the gonadal mosaic status have been published, and the phenotype is usually correlated with peripheral lymphocyte karyotypes, which makes the phenotype prediction imprecise. This study was conducted on 7 Egyptian DSD patients to demonstrate the effect of sex chromosome constitution of both blood lymphocytes and gonadal tissues on the phenotypic manifestations. Conventional cytogenetic and FISH analyses of blood lymphocytes were conducted, and laparoscopy with gonadal biopsy was performed for histopathologic examination and FISH analysis. Gonosomal mosaicism was detected in 3 patients who had a non-mosaic chromosome pattern in blood lymphocytes. Two patients showed the same type of sex chromosome mosaicism in both the blood and gonadal tissues but with different distributions. Two other patients revealed a non-mosaic pattern in both tissues. The present study elucidates the importance of examining sex chromosome mosaicism in gonadal tissues of DSD patients and highlights the critical role of 45,X mosaicism which can lead to serious effects during early gonadal organogenesis.

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Screening for mutations in the SRY gene in patients with mixed gonadal dysgenesis or with Turner syndrome and Y mosaicism

Cited by 15 publications

References 18 publications

The Role of <i>SRY</i> Mutations in the Etiology of Gonadal Dysgenesis in Patients with 45,X/46,XY Disorder of Sex Development and Variants

The Role of <i>SRY</i> Mutations in the Etiology of Gonadal Dysgenesis in Patients with 45,X/46,XY Disorder of Sex Development and Variants

Isodicentric Y chromosomes in Egyptian patients with disorders of sex development (DSD)

Sex Chromosome Mosaicism in the Gonads of DSD Patients: A Karyotype/Phenotype Correlation

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