title: A novel germline KIT mutation (p.L576P) in a family presenting with juvenile onset of multiple gastrointestinal stromal tumors, skin hyperpigmentations, and esophageal stenosis.
abstract: Familial gastrointestinal stromal tumor (GIST) syndrome is a rare autosomal dominant genetic disorder. We report on a kindred in which 3 family members carry a germline mutation (c.1727T>C, p.L576P) in exon 11 of the KIT gene. This mutation was not reported so far in familial GISTs. Apart from multiple GISTs in 2 of the mutation carriers, all of them had multiple hyperpigmented skin macules and a history of achalasia-like stenosis of the esophagus in early childhood. In the index patient >100 tumors and a diffuse Cajal cell hyperplasia of the small bowel occurred. Sequencing of DNA extracted from tumor tissue of one of his GISTs revealed the KIT mutation in exon 11 (c.1727T>C). By array comparative genomic hybridization whole chromosomal gains 3, 5, 7, 9, 12, 15, and 18 were detected. In addition, we could identify a gain on chromosome 4, spanning the KIT gene. Together with the family described here, 24 unrelated cases with proven germline mutations in KIT have been reported. In these families the diagnosis was established from the age of 30 years onwards. Because in 1 patient reported here the GIST was a coincidental finding at the age of 15 years, the tumors might occur at a very young age and remain unnoticed until they-either due to increasing size, ulceration, or malignant progression-become symptomatic. Therefore, we propose to start screening patients with known KIT mutations from a younger age.
authors.affiliation: Institut für Klinische Genetik, Technische Universität Dresden, Dresden, Germany.
authors.forename: Teresa M
authors.initials: TM
authors.lastname: Neuhann
authors.forename: Veit
authors.initials: V
authors.lastname: Mansmann
authors.forename: Sabine
authors.initials: S
authors.lastname: Merkelbach-Bruse
authors.forename: Barbara
authors.initials: B
authors.lastname: Klink
authors.forename: Achim
authors.initials: A
authors.lastname: Hellinger
authors.forename: Heinz-Gert
authors.initials: HG
authors.lastname: Höffkes
authors.forename: Eva
authors.initials: E
authors.lastname: Wardelmann
authors.forename: Hans-Ulrich
authors.initials: HU
authors.lastname: Schildhaus
authors.forename: Sigrid
authors.initials: S
authors.lastname: Tinschert
mesh_terms: D000293:Adolescent; D017668:Age of Onset; D055028:Comparative Genomic Hybridization; D004252:DNA Mutational Analysis; D004940:Esophageal Stenosis / Q000235:genetics*; D005260:Female; D046152:Gastrointestinal Stromal Tumors / Q000235:genetics*; D018095:Germ-Line Mutation; D006801:Humans; D017495:Hyperpigmentation / Q000235:genetics*; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D008875:Middle Aged; D010375:Pedigree; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics*; D055815:Young Adult
chemical_list: D019009:Proto-Oncogene Proteins c-kit