5 and 3 Mutations in PTEN In patient JUV�\16, the MLPA test reve

5 and 3. Mutations in PTEN In patient JUV�\16, the MLPA test revealed an isolated ��deletion�� of PTEN exon 7. Sequencing this exon, we found http://www.selleckchem.com/products/baricitinib-ly3009104.html the heterozygous nonsense mutation c.697C��T;p.Arg233X localised close to the hybridisation site of the MLPA probe for PTEN exon 7. The mutation was also found in the affected father of the index patient. Subsequently, all the remaining mutation�\negative patients were screened for PTEN germline mutations by direct sequencing. Of the 40 patients, 1 (JUV�\18) was found to have a pathogenic splice site mutation in intron 4 (c.253+1G��T). Genotype�Cphenotype correlation The colorectal phenotype of SMAD4 and BMPR1A mutation carriers was indistinguishable: There was no significant difference in the median age at diagnosis of JPS between carriers of the SMAD4 (12 years) and the BMPR1A (14 years) mutations (p=0.

48; table 33).). Both groups had a comparable number and histological spectrum of colorectal polyps. Table 3Genotype�Cphenotype correlation (age at diagnosis, gastric polyposis, hereditary haemorrhagic telangiectasia phenotype) in carriers of SMAD4 and BMPR1A mutations Gastric polyposis In a previous study on 29 unrelated patients with JPS with 12 identified mutations, we found an over�\representation of gastric polyposis among carriers of SMAD4 mutations compared with carriers of BMPR1A mutations.6 A similar trend was observed when only the 27 patients (22 families) with known status of gastric polyposis who had not been analysed in our previous study were considered: 11 of 17 patients with SMAD4 mutations, but none of 11 patients with BMPR1A mutations, had gastric polyposis (p<0.

01). In the combined sample (previously and newly analysed cases) information on results of gastroscopy was available for 30 patients with SMAD4 mutations (20 unrelated index patients and 10 affected relatives) and for 13 patients with BMPR1A mutations (nine index patients and four affected relatives) (table 33).). Of the 30 patients with a SMAD4 mutation, 22 (73%) were found to have gastric polyposis. In contrast, only 1 of the 13 patients (8%) with BMPR1A mutations had gastric polyps (p<0.001). The over�\representation of gastric polyposis in SMAD4 mutation carriers remained true even Drug_discovery when age at gastroscopy was considered. Although the median age at gastroscopy was 35 (range 11�C60) years for patients with SMAD4 mutations and 26 (range 4�C73) years for patients with BMPR1A mutations, the difference was not significant (p=0.71) (table 33). Generally, gastric polyposis in SMAD4 mutation carriers is diagnosed later in life (median age at diagnosis 41 years) compared with diagnosis of colorectal polyps (12 years) (p<0.001).

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