title: Genetic mutations and somatic anomalies in association with 46,XY gonadal dysgenesis.
abstract: OBJECTIVE
  To assess genetic mutations and associated somatic anomalies in a series of patients with 46,XY gonadal dysgenesis (GD).
  
  
  METHODS
  Single center retrospective study.
  
  
  METHODS
  University pediatric hospital.
  
  
  METHODS
  Fourteen patients with 46,XY GD.
  
  
  METHODS
  None.
  
  
  METHODS
  Genotype-phenotype relationship.
  
  
  RESULTS
  The presenting symptom was disorders of sex development (6 patients), primary amenorrhea (2 patients), discordance between 46,XY karyotype and female external genitalia (3 patients), discovery of Müllerian structures at surgery (2 patients), or diagnosed in the evaluation of a gonadal tumor (1 patient). Müllerian structures were shown by ultrasound evaluation in 7 of 13 patients, genitography in 3 of 6 patients and/or surgery in 8 of 10 patients (3 not seen at imaging), or only by histologic examination (1 patient). Three patients had gonadoblastoma and/or seminoma. A mutation was found in 7 patients of whom 2 had family history of reproductive problems and 5 had associated somatic anomalies. The mutations were FOG2/ZFPM2 (1 patient), SRY (2 patients), WT1 (1 patient), or deletions of distal chromosome 9p (3 patients). Among the three other patients with associated anomalies and no mutation, two had ectodermal dysplasia and one had leukemia.
  
  
  CONCLUSIONS
  Mutations were observed in half of the patients with 46,XY GD with Müllerian structures. We also describe for the first time the association between GD and ectodermal dysplasia. Müllerian structures can be found in some cases only by histologic examination, which should be coupled to preventive gonadectomy because of the risk of tumor formation.
authors: Université Paris Descartes and Pediatric Endocrinology Unit, Fondation Ophtalmologique Adolphe de Rothschild, Paris, France.
authors: Claire
authors: C
authors: Bastian
authors: Université Paris Descartes and Pediatric Endocrinology Unit, Fondation Ophtalmologique Adolphe de Rothschild, Paris, France.
authors: Jean-Baptiste
authors: JB
authors: Muller
authors: Assistance Publique-Hôpitaux de Paris, Hôpital Necker-Enfants Malades, Service de chirurgie viscérale pédiatrique, Paris, France.
authors: Stephen
authors: S
authors: Lortat-Jacob
authors: Université Paris Descartes, Institut Pasteur, Paris, France.
authors: Claire
authors: C
authors: Nihoul-Fékété
authors: Human Developmental Genetics, Institut Pasteur, Paris, France.
authors: Joelle
authors: J
authors: Bignon-Topalovic
authors: Human Developmental Genetics, Institut Pasteur, Paris, France. Electronic address: kenneth.mcelreavey@pasteur.fr.
authors: Ken
authors: K
authors: McElreavey
authors: Human Developmental Genetics, Institut Pasteur, Paris, France.
authors: Anu
authors: A
authors: Bashamboo
authors: Université Paris Descartes and Pediatric Endocrinology Unit, Fondation Ophtalmologique Adolphe de Rothschild, Paris, France.
authors: Raja
authors: R
authors: Brauner
mesh_terms: D000568:Amenorrhea / Q000235:genetics / Q000503:physiopathology; D002872:Chromosome Deletion; D002899:Chromosomes, Human, Pair 9; D004252:DNA Mutational Analysis; D004268:DNA-Binding Proteins / Q000235:genetics; D004476:Ectodermal Dysplasia / Q000235:genetics; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006061:Gonadal Dysgenesis, 46,XY / Q000175:diagnosis / Q000235:genetics* / Q000503:physiopathology / Q000601:surgery; D018238:Gonadoblastoma / Q000235:genetics / Q000473:pathology; D006801:Humans; D008297:Male; D009095:Mullerian Ducts / Q000002:abnormalities* / Q000000981:diagnostic imaging / Q000601:surgery; D009154:Mutation; D010051:Ovarian Neoplasms / Q000235:genetics / Q000473:pathology; D010297:Paris; D010641:Phenotype; D012189:Retrospective Studies; D018239:Seminoma / Q000235:genetics / Q000473:pathology; D051876:Sex-Determining Region Y Protein / Q000235:genetics; D013736:Testicular Neoplasms / Q000235:genetics / Q000473:pathology; D014157:Transcription Factors / Q000235:genetics; D014463:Ultrasonography; D025721:WT1 Proteins / Q000235:genetics
chemical_list: D004268:DNA-Binding Proteins; C497745:SRY protein, human; D051876:Sex-Determining Region Y Protein; D014157:Transcription Factors; D025721:WT1 Proteins; C583751:WT1 protein, human; C117427:ZFPM2 protein, human
keywords: 46,XY disorders of sex development; DSD; ectodermal dysplasia; gene mutation; gonadal dysgenesis