title: Novel MLH1 frameshift mutation in an extended hereditary nonpolyposis colorectal cancer family.
abstract: OBJECTIVE
  To present novel frameshift mutation c.31delC [p.L11X] in the MLH1 gene identified in an extended Bulgarian hereditary non-polyposis colorectal cancer (HNPCC) family and to analyze the molecular and clinical findings within the pedigree concerning the proposal of adequate individual prophylactic strategy for all mutation carriers.
  
  
  METHODS
  The pedigree of the family consists of 42 members in four generations. Search for mutations in the MLH1 and hMSH2 genes was performed in the proband. After PCR amplification of all exons including flanking intronic regions, amplicons were directly sequenced.
  
  
  RESULTS
  The mutation was found in nine from the thirteen pedigree members who signed informed consent to participate in the study. In three adenocarcinomas, microsatellite instability and lack of the MLH1 protein expression were detected. The only one tubulovillous adenoma analyzed was microsatellite stable and the MLH1 protein showed an intact staining.
  
  
  CONCLUSIONS
  The newly described mutation c.31delC is HNPCC causative. Besides the typical clinical features of the syndrome, we found a specific pathologic manifestation such as moderate to high differentiated adenocarcinomas of the colon. One of the mutation carriers developed a benign giant cell soft tissue tumor. The primary tumor localizations were frequently extracolonic and detailed yearly gastrointestinal and gynecological examinations have been proposed to the mutation carriers. We emphasize the importance of including the HNPCC genetic counseling and testing as well in the following surveillance of all patients at risk in the services covered by the health insurance in Bulgaria.
authors.affiliation: Laboratory of Molecular Pathology, University Hospital of Obstetrics and Gynecology, 2 Zdrave str., Sofia-1431, Bulgaria. alextanya@excite.com
authors.forename: Tanya-Kirilova
authors.initials: TK
authors.lastname: Kadiyska
authors.forename: Radka-Petrova
authors.initials: RP
authors.lastname: Kaneva
authors.forename: Dimitar-Georgiev
authors.initials: DG
authors.lastname: Nedin
authors.forename: Alexandrina-Borisova
authors.initials: AB
authors.lastname: Alexandrova
authors.forename: Antonina-Todorova
authors.initials: AT
authors.lastname: Gegova
authors.forename: Stoyan-Ganchev
authors.initials: SG
authors.lastname: Lalchev
authors.forename: Tatyana
authors.initials: T
authors.lastname: Christova
authors.forename: Vanio-Ivanov
authors.initials: VI
authors.lastname: Mitev
authors.forename: Juergen
authors.initials: J
authors.lastname: Horst
authors.forename: Nadja
authors.initials: N
authors.lastname: Bogdanova
authors.forename: Ivo-Marinov
authors.initials: IM
authors.lastname: Kremensky
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000230:Adenocarcinoma / Q000235:genetics*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002031:Bulgaria; D002352:Carrier Proteins / Q000235:genetics*; D003123:Colorectal Neoplasms, Hereditary Nonpolyposis / Q000235:genetics*; D004273:DNA, Neoplasm / Q000235:genetics; D005260:Female; D016368:Frameshift Mutation / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic; D005817:Genetic Counseling; D006801:Humans; D008297:Male; D053842:Microsatellite Instability; D008875:Middle Aged; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein / Q000235:genetics; D009687:Nuclear Proteins / Q000235:genetics*; D010375:Pedigree; D017384:Sequence Deletion / Q000235:genetics
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D004273:DNA, Neoplasm; C501486:MLH1 protein, human; D009687:Nuclear Proteins; C497172:MSH2 protein, human; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein