title: Screening of Y chromosome microdeletions in 46,XY partial gonadal dysgenesis and in patients with a 45,X/46,XY karyotype or its variants.
abstract: BACKGROUND
  Partial and mixed gonadal dysgenesis (PGD and MGD) are characterized by genital ambiguity and the finding of either a streak gonad and a dysgenetic testis or two dysgenetic testes. The karyotype in PGD is 46,XY, whereas a 45,X/46,XY mosaicism or its variants (more than two lineages and/or structural abnormalities of the Y chromosome) is generally found in MGD. Such mosaics are also compatible with female phenotype and Turner syndrome, ovotesticular disorder of sex development, and infertility in men with normal external genitalia. During the last few years, evidences of a linkage between Y microdeletions and 45,X mosaicism have been reported. There are also indications that the instability caused by such deletions might be more significant in germ cells. The aim of this work was to investigate the presence of Y chromosome microdeletions in individuals with PGD and in those with 45,X/46,XY mosaicism or its variants and variable phenotypes.
  
  
  METHODS
  Our sample comprised 13 individuals with PGD and 15 with mosaicism, most of them with a MGD phenotype (n = 11). Thirty-six sequence tagged sites (STS) spanning the male specific region (MSY) on the Y chromosome (Yp, centromere and Yq) were analyzed by multiplex PCR and some individual reactions.
  
  
  RESULTS
  All STS showed positive amplifications in the PGD group. Conversely, in the group with mosaicism, six individuals with MGD had been identified with Yq microdeletions, two of them without structural abnormalities of the Y chromosome by routine cytogenetic analysis. The deleted STSs were located within AZFb and AZFc (Azoospermia Factor) regions, which harbor several genes responsible for spermatogenesis.
  
  
  CONCLUSIONS
  Absence of deletions in individuals with PGD does not confirm the hypothesis that instability of the Y chromosome in the gonads could be one of the causes of such condition. However, deletions identified in the second group indicate that mosaicism may be associated with Y chromosome abnormalities detectable only at the molecular level. If patients with mosaicism and Y microdeletions reared as males decide to undergo in vitro fertilization, Y chromosomes which tend to be unstable during cell division may be transmitted to offspring.
authors.forename: Ana Paula
authors.initials: AP
authors.lastname: dos Santos
authors.forename: Juliana Gabriel Ribeiro
authors.initials: JG
authors.lastname: Andrade
authors.forename: Cristiane Santos Cruz
authors.initials: CS
authors.lastname: Piveta
authors.forename: Juliana
authors.initials: J
authors.lastname: de Paulo
authors.forename: Gil
authors.initials: G
authors.lastname: Guerra
authors.forename: Maricilda Palandi
authors.initials: MP
authors.lastname: de Mello
authors.affiliation: Department of Medical Genetics, Faculty of Medical Sciences, University of Campinas - UNICAMP, Tessália Vieira de Camargo Street, 126 - Zip Code, 13083-887 Campinas, SP, Brazil. atmg@uol.com.br.
authors.forename: Andréa Trevas
authors.initials: AT
authors.lastname: Maciel-Guerra
mesh_terms: D000293:Adolescent; D002872:Chromosome Deletion; D041322:Chromosomes, Human, Y; D020224:Expressed Sequence Tags; D005260:Female; D006059:Gonadal Dysgenesis / Q000235:genetics; D006060:Gonadal Dysgenesis, Mixed / Q000235:genetics*; D006801:Humans; D007248:Infertility, Male; D059785:Karyotype; D008297:Male; D009030:Mosaicism; D012729:Sex Chromosome Aberrations; D058533:Sex Chromosome Disorders of Sex Development; D013737:Testis / Q000002:abnormalities; D055815:Young Adult