title: A novel intronic mutation and a missense mutation of MEN1 identified in two Chinese families with multiple endocrine neoplasia type 1.
abstract: BACKGROUND
  Multiple endocrine neoplasia type 1 (MEN1) caused by MEN1 mutation is widely recognized. To date, 14 novel mutations were reported in Chinese and intronic mutations are getting more attention.
  
  
  OBJECTIVE
  To explore clinical features and MEN1 mutations in two Chinese families suffering from MEN1.
  
  
  METHODS
  Nineteen individuals (10 males and 9 females) from two unrelated families with MEN1 were studied. Mutations of MEN1 were analyzed by direct sequencing of PCR products. In vitro splicing analysis was also performed with minigenes containing both wildtype and novel mutant fragments. Through the RNAstructure program, we analyzed the secondary structure of the wild type MEN1 pre-mRNA and then introduced T>G mutation at +2 donor splice site of intron 7.
  
  
  RESULTS
  Clinical features of 3 patients in two families were described, and 5 individuals were proven to be carriers of MEN1 mutation without apparent symptoms. A novel splicing site mutation of the intron 7 (IVS7+2 T→G) was identified in the first family. In vitro analysis also verified this mutation caused the aberrant splicing of MEN1 mRNA. With the RNAstructure program, we could figure out that the global secondary structure as well as the number of stems and loops of pre-mRNA greatly changed after this mutation. The mutation c. 1227 C>A (C409X) was identified in another family, which also caused the truncation of menin.
  
  
  CONCLUSIONS
  We reported a novel intronic mutation and a missense mutations in two Chinese families suffering from MEN1.
authors.affiliation: Department of Endocrinology, Shanghai Ninth People's Hospital, Shanghai, China.
authors.forename: B
authors.initials: B
authors.lastname: Han
authors.forename: Z Y
authors.initials: ZY
authors.lastname: Song
authors.forename: J J
authors.initials: JJ
authors.lastname: Wu
authors.forename: W
authors.initials: W
authors.lastname: Liu
authors.forename: B L
authors.initials: BL
authors.lastname: Liu
authors.forename: X P
authors.initials: XP
authors.lastname: Ye
authors.forename: X
authors.initials: X
authors.lastname: Chen
authors.forename: C M
authors.initials: CM
authors.lastname: Pan
authors.forename: H Y
authors.initials: HY
authors.lastname: Xu
authors.forename: L
authors.initials: L
authors.lastname: Li
authors.forename: H
authors.initials: H
authors.lastname: Zhu
authors.forename: Y L
authors.initials: YL
authors.lastname: Lu
authors.forename: W L
authors.initials: WL
authors.lastname: Wu
authors.forename: M D
authors.initials: MD
authors.lastname: Chen
authors.forename: H D
authors.initials: HD
authors.lastname: Song
authors.forename: J
authors.initials: J
authors.lastname: Qiao
mesh_terms: D000328:Adult; D000369:Aged, 80 and over; D044466:Asian People / Q000235:genetics; D001483:Base Sequence; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007223:Infant; D007438:Introns / Q000235:genetics; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D018761:Multiple Endocrine Neoplasia Type 1 / Q000235:genetics*; D020125:Mutation, Missense / Q000502:physiology; D009690:Nucleic Acid Conformation; D010375:Pedigree; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D012322:RNA Precursors / Q000737:chemistry / Q000235:genetics
chemical_list: C105373:MEN1 protein, human; D011518:Proto-Oncogene Proteins; D012322:RNA Precursors