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Disorders of sex development: a genetic study of patients in a multidisciplinary clinic.

Laino L, Majore S, Preziosi N, Grammatico B, De Bernardo C, Scommegna S, Rapone AM, Marrocco G, Bottillo I, Grammatico P - Endocr Connect (2014)

Bottom Line: Incomplete knowledge of the genetic mechanisms involved in sex development results in a low probability of determining the molecular definition of the genetic defect in many of the patients.In this study, we describe the clinical, cytogenetic, and molecular study of 88 cases with DSD, including 29 patients with 46,XY and disorders in androgen synthesis or action, 18 with 46,XX and disorders in androgen excess, 17 with 46,XY and disorders of gonadal (testicular) development, 11 classified as 46,XX other, eight with 46,XX and disorders of gonadal (ovarian) development, and five with sex chromosome anomalies.In conclusion, our results highlight the fact that each category of DSD is related to a large number of different DNA alterations, thus requiring multiple genetic studies to achieve a precise etiological diagnosis for each patient.

View Article: PubMed Central - PubMed

Affiliation: Department of Molecular MedicineMedical Genetics, San Camillo-Forlanini Hospital, Sapienza University, A.O. San Camillo-Forlanini, Padiglione Morgagni, I piano, UOC Laboratorio di Genetica Medica, Circonvallazione Gianicolense 87, Rome 00152, ItalyDepartment of Pediatrics and HematologySan Camillo-Forlanini Hospital, A.O. San Camillo-Forlanini, Padiglione Baccelli, II piano, Pediatria ed Ematologia Pediatrica, Circonvallazione Gianicolense 87, Rome 00152, ItalyPsychology DepartmentSan Camillo-Forlanini Hospital, A.O. San Camillo-Forlanini, Dipartimento di Pscicologia, Circonvallazione Gianicolense 87, Rome 00152, ItalyDepartment of Pediatric SurgerySan Camillo-Forlanini Hospital, A.O. San Camillo-Forlanini, Padiglione Baccelli, II piano, Pediatria ed Ematologia Pediatrica, Circonvallazione Gianicolense 87, Rome 00152, Italy.

No MeSH data available.


Related in: MedlinePlus

Positions of the identified point mutations along the coding sequences of the SRY, AMH, SRD5A2, NR5A1, CYP11B1, AR, RSPO1, and CYP21A2 genes. Exons are symbolized by gray boxes and introns (not in scale) by black lines. Functional protein domains are represented by black stripes above each gene diagram. HMG, High-Mobility Group; TGFB, transforming growth factor Beta; ZnF_C4, c4 zinc finger; HOLI, ligand-binding domain of hormone receptors; FU, furin-like repeats; TSP1, thrombospondin type 1 repeats. Protein domains were predicted using the SMART software (30).
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fig4: Positions of the identified point mutations along the coding sequences of the SRY, AMH, SRD5A2, NR5A1, CYP11B1, AR, RSPO1, and CYP21A2 genes. Exons are symbolized by gray boxes and introns (not in scale) by black lines. Functional protein domains are represented by black stripes above each gene diagram. HMG, High-Mobility Group; TGFB, transforming growth factor Beta; ZnF_C4, c4 zinc finger; HOLI, ligand-binding domain of hormone receptors; FU, furin-like repeats; TSP1, thrombospondin type 1 repeats. Protein domains were predicted using the SMART software (30).

Mentions: In total, we found a genetic alteration in 56 out of 88 (64%) patients (Table 2). Figure 3 summarizes the genetic tests, and the respective results, performed on patients with 46,XX disorders of ovarian development, 46,XX androgen excess, 46,XX other, 46,XY disorders of testicular development, and 46,XY disorders in androgen synthesis/action. The positions of all the identified point mutations along the SRY, AMH, SRD5A2, NR5A1, CYP11B1, AR, RSPO1, and CYP21A2 coding sequences are shown in Fig. 4.


Disorders of sex development: a genetic study of patients in a multidisciplinary clinic.

Laino L, Majore S, Preziosi N, Grammatico B, De Bernardo C, Scommegna S, Rapone AM, Marrocco G, Bottillo I, Grammatico P - Endocr Connect (2014)

Positions of the identified point mutations along the coding sequences of the SRY, AMH, SRD5A2, NR5A1, CYP11B1, AR, RSPO1, and CYP21A2 genes. Exons are symbolized by gray boxes and introns (not in scale) by black lines. Functional protein domains are represented by black stripes above each gene diagram. HMG, High-Mobility Group; TGFB, transforming growth factor Beta; ZnF_C4, c4 zinc finger; HOLI, ligand-binding domain of hormone receptors; FU, furin-like repeats; TSP1, thrombospondin type 1 repeats. Protein domains were predicted using the SMART software (30).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4195882&req=5

fig4: Positions of the identified point mutations along the coding sequences of the SRY, AMH, SRD5A2, NR5A1, CYP11B1, AR, RSPO1, and CYP21A2 genes. Exons are symbolized by gray boxes and introns (not in scale) by black lines. Functional protein domains are represented by black stripes above each gene diagram. HMG, High-Mobility Group; TGFB, transforming growth factor Beta; ZnF_C4, c4 zinc finger; HOLI, ligand-binding domain of hormone receptors; FU, furin-like repeats; TSP1, thrombospondin type 1 repeats. Protein domains were predicted using the SMART software (30).
Mentions: In total, we found a genetic alteration in 56 out of 88 (64%) patients (Table 2). Figure 3 summarizes the genetic tests, and the respective results, performed on patients with 46,XX disorders of ovarian development, 46,XX androgen excess, 46,XX other, 46,XY disorders of testicular development, and 46,XY disorders in androgen synthesis/action. The positions of all the identified point mutations along the SRY, AMH, SRD5A2, NR5A1, CYP11B1, AR, RSPO1, and CYP21A2 coding sequences are shown in Fig. 4.

Bottom Line: Incomplete knowledge of the genetic mechanisms involved in sex development results in a low probability of determining the molecular definition of the genetic defect in many of the patients.In this study, we describe the clinical, cytogenetic, and molecular study of 88 cases with DSD, including 29 patients with 46,XY and disorders in androgen synthesis or action, 18 with 46,XX and disorders in androgen excess, 17 with 46,XY and disorders of gonadal (testicular) development, 11 classified as 46,XX other, eight with 46,XX and disorders of gonadal (ovarian) development, and five with sex chromosome anomalies.In conclusion, our results highlight the fact that each category of DSD is related to a large number of different DNA alterations, thus requiring multiple genetic studies to achieve a precise etiological diagnosis for each patient.

View Article: PubMed Central - PubMed

Affiliation: Department of Molecular MedicineMedical Genetics, San Camillo-Forlanini Hospital, Sapienza University, A.O. San Camillo-Forlanini, Padiglione Morgagni, I piano, UOC Laboratorio di Genetica Medica, Circonvallazione Gianicolense 87, Rome 00152, ItalyDepartment of Pediatrics and HematologySan Camillo-Forlanini Hospital, A.O. San Camillo-Forlanini, Padiglione Baccelli, II piano, Pediatria ed Ematologia Pediatrica, Circonvallazione Gianicolense 87, Rome 00152, ItalyPsychology DepartmentSan Camillo-Forlanini Hospital, A.O. San Camillo-Forlanini, Dipartimento di Pscicologia, Circonvallazione Gianicolense 87, Rome 00152, ItalyDepartment of Pediatric SurgerySan Camillo-Forlanini Hospital, A.O. San Camillo-Forlanini, Padiglione Baccelli, II piano, Pediatria ed Ematologia Pediatrica, Circonvallazione Gianicolense 87, Rome 00152, Italy.

No MeSH data available.


Related in: MedlinePlus