title: DNA sequence variations of the entire anti-Mullerian hormone (AMH) gene promoter and AMH protein expression in patients with the Mayer-Rokitanski-Kuster-Hauser syndrome.
abstract: BACKGROUND
  The etiology of the Mayer-Rokitanski-Kuster-Hauser (MRKH) syndrome, where congenitally the Mullerian ducts fail to develop into the uterus, cervix and upper vagina, along with other malformations, is unresolved. Anti-Mullerian hormone (AMH) signal transduction inducing the degradation of Mullerian ducts in males is implicated in the MRKH syndrome. This study examined if DNA sequence variations are responsible for the activation of AMH and aberrant hormone levels in MRKH patients.
  
  
  METHODS
  The entire AMH promoter and 3' regulatory elements of the constitutively expressed splicing factor SF3a2 were sequenced in 30 MRKH patients and genotyped in 48 control individuals using matrix-assisted laser desorption/ionization-time-of-flight mass spectronomy. Ovarian AMH promoter function was correlated with protein expression in plasma and peritoneal fluid of MRKH patients.
  
  
  RESULTS
  Of six identified AMH promoter variations, two at positions -639 (SP1-binding site) and -210 [steroidogenic factor (SF)1-binding site] were homozygote in 73% of patients, and 69% of control individuals, destroying the SP1-binding site. AMH protein levels in plasma and peritoneal fluid from patients were equivalent to control individuals, however in three patients plasma levels were abnormally high.
  
  
  CONCLUSIONS
  AMH is an important indicator for ovarian function. AMH promoter sequence variations or the previously proposed SF3a2-AMH fusion co-transcripts cannot be responsible for aberrant AMH expression leading to Mullerian duct degradation.
authors.affiliation: Department of Gynaecology and Obstetrics and Department of Biochemistry at the University of Erlangen-Nuremberg, Erlangen, Germany.
authors.forename: P
authors.initials: P
authors.lastname: Oppelt
authors.forename: P L
authors.initials: PL
authors.lastname: Strissel
authors.forename: A
authors.initials: A
authors.lastname: Kellermann
authors.forename: S
authors.initials: S
authors.lastname: Seeber
authors.forename: A
authors.initials: A
authors.lastname: Humeny
authors.forename: M W
authors.initials: MW
authors.lastname: Beckmann
authors.forename: R
authors.initials: R
authors.lastname: Strick
mesh_terms: D000015:Abnormalities, Multiple / Q000097:blood / Q000235:genetics / Q000378:metabolism; D000293:Adolescent; D000328:Adult; D000483:Alleles; D054304:Anti-Mullerian Hormone; D001202:Ascitic Fluid / Q000378:metabolism; D001483:Base Sequence; D016022:Case-Control Studies; D004247:DNA / Q000235:genetics*; D005091:Exons; D005260:Female; D015870:Gene Expression; D014644:Genetic Variation; D005836:Genitalia, Female / Q000002:abnormalities*; D006023:Glycoproteins / Q000097:blood / Q000235:genetics* / Q000378:metabolism*; D006801:Humans; D008875:Middle Aged; D009095:Mullerian Ducts / Q000196:embryology; D009698:Nucleoproteins / Q000235:genetics; D010641:Phenotype; D011401:Promoter Regions, Genetic; D000072260:RNA Splicing Factors; D016601:RNA-Binding Proteins / Q000235:genetics; D013577:Syndrome; D013735:Testicular Hormones / Q000097:blood / Q000235:genetics* / Q000378:metabolism*
chemical_list: D006023:Glycoproteins; D009698:Nucleoproteins; D000072260:RNA Splicing Factors; D016601:RNA-Binding Proteins; C083433:SF3A2 protein, human; D013735:Testicular Hormones; D054304:Anti-Mullerian Hormone; D004247:DNA