A case of a child with an APC pathogenic mutation, aberrant expression of splice variants and positive family history of FAP.
Familial adenomatous polyposis is an autosomal dominant hereditary disease characterized by the appearance of hundreds to thousands of colorectal adenomatous polyps; if left untreated, there is nearly a 100% lifetime risk of colorectal cancer. In the present case, adenomatous polyps were observed at 6 years of age. Unlike our previous assumption, adenomatous polyps were detected by colonoscopy at <10 years of age. Considering the clinical importance of early diagnosis, we report this case involving germline adenomatous polyposis coli mutation (c.1958G > C, GenBank: M74088.1) that caused an increase in the isoform without exon 15. Although this isoform has been reported previously, it remains controversial whether the variant is pathogenic or not because it was observed both in patients with familial adenomatous polyposis and in normal controls. Nonetheless, due to quantitative distortion of splice variants in adenomatous polyposis coli transcripts and the early development of adenomatous polyps, we believe that this variant may be pathogenic.
Clinical Genetic Oncology, Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo.
Keiko
K
Taki
Clinical Genetic Oncology, Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo.
Yasuyoshi
Y
Sato
Clinical Genetic Oncology, Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo.
Yuri
Y
Sato
Clinical Genetic Oncology, Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo.
Yuumi
Y
Ashihara
Division of Gastroenterology, Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo.
Akiko
A
Chino
Division of Gastroenterology, Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo.
Masahiro
M
Igarashi
Division of Gastroenterology and Hepatology, Department of Internal Medicine, Toho University Ohashi Medical Center, Tokyo.
Koichiro
K
Sato
Division of Gastroenterology and Hepatology, Department of Internal Medicine, Toho University Ohashi Medical Center, Tokyo.
Tomoyuki
T
Kitagawa
Division of Gastroenterology and Hepatology, Department of Internal Medicine, Toho University Ohashi Medical Center, Tokyo.
Iruru
I
Maetani
Department of Pediatrics, Ohashi Hospital, Toho University School of Medicine, Tokyo, Japan.
Chieko
C
Nemoto
Department of Pediatrics, Ohashi Hospital, Toho University School of Medicine, Tokyo, Japan.
Kiyoto
K
Nasuno
Department of Pediatrics, Ohashi Hospital, Toho University School of Medicine, Tokyo, Japan.
Takashi
T
Sekine
Clinical Genetic Oncology, Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo marai@jfcr.or.jp.
Masami
M
Arai
D011125:Adenomatous Polyposis Coli / Q000175:diagnosis* / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D025601:Adenomatous Polyposis Coli Protein / Q000235:genetics*; D044466:Asian People; D002648:Child; D003110:Colonic Neoplasms / Q000235:genetics; D003113:Colonoscopy; D020022:Genetic Predisposition to Disease; D005820:Genetic Testing; D018095:Germ-Line Mutation; D006579:Heterozygote; D006801:Humans; D008297:Male; D010375:Pedigree; D020033:Protein Isoforms / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction
C555337:APC protein, human; D025601:Adenomatous Polyposis Coli Protein; D020033:Protein Isoforms
APC; FAP; splicing mutation