Abstract:
:The DNA mismatch repair genes MSH2 and MLH1 have been shown to account for a major share of hereditary non-polyposis colorectal cancer (HNPCC). We searched for germline mutations in these genes in 35 HNPCC kindreds fulfilling the Amsterdam diagnostic criteria and in a further 20 kindreds with an average of four affected members per family but not meeting the formal criteria. We first screened for truncations by reverse transcriptase (RT)-PCR. If no mutation was found, we screened genomic DNA by a novel application of two-dimensional (2-D) DNA electrophoresis that allows the simultaneous study of all exons of each gene. All abnormalities were followed up by sequencing. Eight different pathogenic germline mutations were found, two in MSH2 and six in MLH1. We report three major conclusions. First, these mutations together accounted for 86% (30/35) of the kindreds meeting the Amsterdam criteria, but only 30% (6/20) of the remaining kindreds, suggesting differences in etiology. Second, MLH1 was involved in > 90% (34/36) of kindreds with a known predisposing mutation, suggesting that mutations in the MLH1 gene are responsible for most HNPCC kindreds in Finland. Third, our results indicate that the successive application of RT-PCR and 2-D DNA electrophoresis is a sensitive and efficient method for mutation screening in typical HNPCC.
journal_name
Hum Mol Genetjournal_title
Human molecular geneticsauthors
Nyström-Lahti M,Wu Y,Moisio AL,Hofstra RM,Osinga J,Mecklin JP,Järvinen HJ,Leisti J,Buys CH,de la Chapelle A,Peltomäki Pdoi
10.1093/hmg/5.6.763subject
Has Abstractpub_date
1996-06-01 00:00:00pages
763-9issue
6eissn
0964-6906issn
1460-2083pii
6d0002journal_volume
5pub_type
杂志文章abstract::Ciliary trafficking defects underlie the pathogenesis of severe human ciliopathies, including Joubert Syndrome (JBTS), Bardet-Biedl Syndrome, and some forms of retinitis pigmentosa (RP). Mutations in the ciliary protein RPGR (retinitis pigmentosa GTPase regulator) are common causes of RP-associated photoreceptor degen...
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