Hereditary non-polyposis colorectal cancer (HNPCC): New germline mutation (190-191 del AA) in the human MLH1 gene and review of clinical guidelines for surveillance of affected families

\Hereditary non-polyposis colorectal cancer (HNPCC) is one of the most comm on genetic diseases comprising at least 5-6% of all colorectal cancers. It is characterized by early onset and mostly right-sided tumors (proximal to the splenic flecture). Molecular analyses are useful methods for diagnosis in index patients and for the detection of risk persons in affected familie s. A 37-year-old female patient whose family history fulfilled the criteria fo r hereditary non-polyposis colorectal cancer (HNPCC) was studied using PCR and DNA sequencing for the detection of mutations in the mismatch repair ge nes hMSH2 and hMLH1. Additionally, literature was reviewed (MEDLINE researc h until 2000) concerning clinical guidelines for surveillance in HNPCC fami lies. A new deletion of two adenosine nucleotides (190-191del AA) at codon 64 in exon 2 of the hMLH1 gene was found. The frameshift led to a stop codon at a mino acid position 75. This mutation is considered to be disease causing in the development of the colorectal cancer of this family. Six publications with detailed recommendations for the surveillance of risk persons were found in the literature. Following their guidelines, colonosc opy is recommended from 20-30 years on for members of a family who fulfills either the Amsterdam criteria or the Bethesda criteria in combination with a detection of microsatellite instability. Female risk persons should be i nvestigated gynecologically, including a transvaginal ultrasound examinatio n, from 25-35 years on for the early detection of endometrial or ovarian ca ncer. Recommendations for gastroscopy, abdominal ultrasound examination and urine analysis are not given in all publications. Genetic counseling is re commended from 18 years on for all members of affected families.