Major contribution from recurrent alterations and MSH6 mutations in the Danish Lynch syndrome population.
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Major contribution from recurrent alterations and MSH6 mutations in the Danish Lynch syndrome population. / Nilbert, Mef; Wikman, Friedrik P; Hansen, Thomas V O; Krarup, Henrik B; Orntoft, Torben F; Nielsen, Finn C; Sunde, Lone; Gerdes, Anne-Marie; Cruger, Dorthe; Timshel, Susanne; Bisgaard, Søs Marie Luise; Bernstein, Inge; Okkels, Henrik; Nilbert, Mef; Wikman, Friedrik; Hansen, Thomas; Krarup, Henrik; Orntoft, Torben; Nielsen, Finn; Sunde, Lone; Gerdes, Anne-Marie; Cruger, Dorthe; Timshel, Susanne; Bisgaard, Marie-Louise; Bernstein, Inge; Okkels, Henrik.
I: Familial Cancer, Bind 8, Nr. 1, 2009, s. 75-83.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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TY - JOUR
T1 - Major contribution from recurrent alterations and MSH6 mutations in the Danish Lynch syndrome population.
AU - Nilbert, Mef
AU - Wikman, Friedrik P
AU - Hansen, Thomas V O
AU - Krarup, Henrik B
AU - Orntoft, Torben F
AU - Nielsen, Finn C
AU - Sunde, Lone
AU - Gerdes, Anne-Marie
AU - Cruger, Dorthe
AU - Timshel, Susanne
AU - Bisgaard, Søs Marie Luise
AU - Bernstein, Inge
AU - Okkels, Henrik
AU - Nilbert, Mef
AU - Wikman, Friedrik
AU - Hansen, Thomas
AU - Krarup, Henrik
AU - Orntoft, Torben
AU - Nielsen, Finn
AU - Sunde, Lone
AU - Gerdes, Anne-Marie
AU - Cruger, Dorthe
AU - Timshel, Susanne
AU - Bisgaard, Marie-Louise
AU - Bernstein, Inge
AU - Okkels, Henrik
N1 - Keywords: Adaptor Proteins, Signal Transducing; Colorectal Neoplasms, Hereditary Nonpolyposis; DNA Mutational Analysis; DNA-Binding Proteins; Denmark; Female; Founder Effect; Humans; Male; Middle Aged; MutS Homolog 2 Protein; Mutation; Nuclear Proteins
PY - 2009
Y1 - 2009
N2 - An increasing number of mismatch-repair (MMR) gene mutations have been identified in hereditary nonpolyposis colorectal cancer (HNPCC) or Lynch syndrome. This study presents the population-based Danish MMR gene mutation profile, which contains 138 different MMR gene alterations. Among these, 88 mutations in 164 families are considered pathogenic and an additional 50 variants from 76 families are considered to represent variants of unknown pathogenicity. The different MMR genes contribute to 40% (MSH2), 29% (MLH1), and 22% (MSH6) of the mutations and the Danish population thus shows a considerably higher frequency of MSH6 mutations than previously described. Although 69/88 (78%) pathogenic mutations were present in a single family, previously recognized recurrent/founder mutations were causative in 75/137 (55%) MLH1/MSH2 mutant families. In addition, the Danish MLH1 founder mutation c.1667+2_1667_+8TAAATCAdelinsATTT was identified in 14/58 (24%) MLH1 mutant families. The Danish Lynch syndrome population thus demonstrates that MSH6 mutations and recurrent/founder mutations have a larger contribution than previously recognized, which implies that the MSH6 gene should be included in routine diagnostics and suggests that directed analysis of recurrent/founder mutations may be feasible e.g. in families were diagnostic material is restricted to archival tissue.
AB - An increasing number of mismatch-repair (MMR) gene mutations have been identified in hereditary nonpolyposis colorectal cancer (HNPCC) or Lynch syndrome. This study presents the population-based Danish MMR gene mutation profile, which contains 138 different MMR gene alterations. Among these, 88 mutations in 164 families are considered pathogenic and an additional 50 variants from 76 families are considered to represent variants of unknown pathogenicity. The different MMR genes contribute to 40% (MSH2), 29% (MLH1), and 22% (MSH6) of the mutations and the Danish population thus shows a considerably higher frequency of MSH6 mutations than previously described. Although 69/88 (78%) pathogenic mutations were present in a single family, previously recognized recurrent/founder mutations were causative in 75/137 (55%) MLH1/MSH2 mutant families. In addition, the Danish MLH1 founder mutation c.1667+2_1667_+8TAAATCAdelinsATTT was identified in 14/58 (24%) MLH1 mutant families. The Danish Lynch syndrome population thus demonstrates that MSH6 mutations and recurrent/founder mutations have a larger contribution than previously recognized, which implies that the MSH6 gene should be included in routine diagnostics and suggests that directed analysis of recurrent/founder mutations may be feasible e.g. in families were diagnostic material is restricted to archival tissue.
U2 - 10.1007/s10689-008-9199-3
DO - 10.1007/s10689-008-9199-3
M3 - Journal article
VL - 8
SP - 75
EP - 83
JO - Familial Cancer
JF - Familial Cancer
SN - 1389-9600
IS - 1
ER -
ID: 15790378