title: Persistent Mullerian duct syndrome caused by both a 27-bp deletion and a novel splice mutation in the MIS type II receptor gene.
abstract: BACKGROUND
  Persistent Mullerian duct syndrome (PMDS) is a rare form of male pseudohermaphroditism that is characterized by the persistence of Mullerian derivatives in otherwise normally virilized males. Mutations of the Mullerian inhibiting substance (MIS) gene or the MIS type II receptor (MISRII) gene have been identified in PMDS patients with autosomal recessive transmission. We analyzed a compound heterozygote PMDS patient who had a 27-bp deletion in exon 10 in one allele and a novel mutation in intron 5 in the other allele of the MISRII gene.
  
  
  METHODS
  Whole blood and tissue samples were obtained from a one-month-old 46,XY male with persistent PMDS and the MISRII gene was sequenced and compared to his mother's genomic DNA and that of 22 normal individuals. Serum MIS and the reproductive hormones were measured by standard immunoassays.
  
  
  RESULTS
  The patient's hormone levels were normal but the gene for MISRII contained several mutations, a 27-bp deletion in exon 10 on one allele (one of the most common mutations in PMDS) and a novel mutation in intron 5 in the other allele that altered splicing, resulting in retention of the intron and a frameshift, introducing a stop codon. Other mutations in introns 6 and 9 and in exon 11 might not be functionally significant.
  
  
  CONCLUSIONS
  This case reveals a novel mutation in the MISRII gene involving intronic sequences, which when coexisting with the already identified 27-bp deletion in exon 10, leads to PMDS.
authors.affiliation: Department of Surgery, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114, USA.
authors.forename: Makiko
authors.initials: M
authors.lastname: Hoshiya
authors.forename: Benjamin P
authors.initials: BP
authors.lastname: Christian
authors.forename: William J
authors.initials: WJ
authors.lastname: Cromie
authors.forename: Hyung
authors.initials: H
authors.lastname: Kim
authors.forename: Yong
authors.initials: Y
authors.lastname: Zhan
authors.forename: David T
authors.initials: DT
authors.lastname: MacLaughlin
authors.forename: Patricia K
authors.initials: PK
authors.lastname: Donahoe
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D004252:DNA Mutational Analysis; D017931:DNA Primers / Q000737:chemistry; D012734:Disorders of Sex Development / Q000235:genetics* / Q000601:surgery; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D008969:Molecular Sequence Data; D009095:Mullerian Ducts / Q000002:abnormalities* / Q000601:surgery; D017354:Point Mutation; D012326:RNA Splicing / Q000235:genetics*; D012333:RNA, Messenger / Q000032:analysis; D018000:Receptors, Peptide / Q000235:genetics*; D018125:Receptors, Transforming Growth Factor beta; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017384:Sequence Deletion; D013577:Syndrome
chemical_list: D017931:DNA Primers; D012333:RNA, Messenger; D018000:Receptors, Peptide; D018125:Receptors, Transforming Growth Factor beta; C084621:anti-Mullerian hormone receptor