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J Med Genet 38:863-867 doi:10.1136/jmg.38.12.863
  • Letters to the editor

A silent mutation in exon 14 of theAPC gene is associated with exon skipping in a FAP family

  1. Mariapina Monteraa,
  2. Francesca Piaggioa,
  3. Cristiana Marcheseb,
  4. Viviana Gismondic,
  5. Alessandro Stellad,
  6. Nicoletta Restad,
  7. Liliana Varescoc,
  8. Ginevra Guantid,
  9. Cristina Marenia
  1. aDipartimento di Medicina Interna, Università di Genova, Viale Benedetto XV/6, 16132 Genova, Italy, bOspedale Mauriziano Umberto I, Torino, Italy, cIstituto Nazionale per la Ricerca sul Cancro, Genova, Italy, dDipartimento di Medicina Interna e del Lavoro, Sezione di Genetica Medica, Università di Bari, Italy
  1. Dr Mareni, mareni{at}unige.it

    Editor—Familial adenomatous polyposis (FAP) is an autosomal dominantly inherited disorder characterised by the development of hundreds to thousands of adenomatous polyps in the colon and rectum. If left untreated, there is a very high risk of colorectal cancer. Adenomatous polyps may also develop proximally in the stomach and the distal part of the duodenum. FAP is also associated with a variety of extracolonic benign and malignant manifestations, including congenital hypertrophy of the retinal pigment epithelium (CHRPE), dental abnormalities, desmoid tumours, osteomas, epidermoid cysts, hepatoblastoma, and thyroid neoplasia.1 Germline mutations of the APC gene localised on chromosome 5q21.22 are responsible for FAP.2 3 APC is a tumour suppressor gene encoding a 2843 amino acid protein, which contains multiple functional domains and which mediates growth regulatory signals by its association with a variety of cytoplasmic proteins. More than 300 differentAPC mutations have so far been identified distributed throughout the whole gene, with a higher concentration in the 5′ part of exon 15 (codons 713-1597).4 5 The majority of mutations are predicted to introduce premature termination signals resulting from single nucleotide alterations, small insertions or deletions, or splice site mutations that lead to truncation of the normal protein product.4 Missense mutations have rarely been reported and their functional implications are often unclear.6 7 Larger deletions and insertions have been described, as well as genomic rearrangements resulting from recombinations mediated by Alu elements which cause inappropriate exon splicing.8-10 Isoforms of APCtranscripts lacking exon 9, exon 10A, and exon 14 encoded sequences have been reported.2 11-13 Isoforms lacking exon 9 or exon 14 owing to splice site mutations have also been associated with a FAP phenotype.14-17

    In this study, we describe a G→T transversion at nucleotide position 1869 in exon 14 which gives …