Eight novel CARD15 variants detected by DNA sequence analysis of the CARD15 gene in 111 patients with inflammatory bowel disease.
We performed a limited DNA sequence analysis of the CARD15 gene in 89 patients with Crohn's disease (CD), 19 patients with ulcerative colitis (UC), and three patients with indeterminate colitis (IC), who were heterozygous carriers of one of the common CARD15 mutations [c.2104C>T (p.R702W), c.2722G>C (p.G908R), or c.3019_3020insC (p.Leu1007fsX1008)], the c.2462+10A>C variant, or of a new amino acid substitution in the 3'-end of exon 4. CARD15 exons 4, 5, 6, 8, and 11 were amplified by PCR and completely sequenced, thereby theoretically covering 73.9% of the described CARD15 variants and 96.6% of the mutated alleles. Using this approach, eight novel amino acid substitutions [c.1171C>T (p.R391C), c.1387C>G (p.P463A), c.2138G>A (p.R713H), c.2278C>T (p.R760C), c.2368C>T (p.R790W), c.2371C>T (p.R791W), c.2475C>G (p.N825K), and c.2546C>T (p.A849V)] were detected in six CD and two IC patients, and one UC patient. A severe disease phenotype was observed especially in patients who are compound-heterozygous for a common and a novel CARD15 mutation.
Department of Clinical Chemistry-Grosshadern, Ludwig-Maximilians-University Munich, Marchioninistr. 15, 81377 Munich, Germany.
Fabian
F
Schnitzler
Stephan
S
Brand
Tanja
T
Staudinger
Simone
S
Pfennig
Katrin
K
Hofbauer
Julia
J
Seiderer
Cornelia
C
Tillack
Burkhard
B
Göke
Thomas
T
Ochsenkühn
Peter
P
Lohse
D000293:Adolescent; D000328:Adult; D019943:Amino Acid Substitution / Q000235:genetics; D004252:DNA Mutational Analysis; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000235:genetics*; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics*; D008297:Male; D009154:Mutation; D053473:Nod2 Signaling Adaptor Protein; D010641:Phenotype; D011110:Polymorphism, Genetic
D047908:Intracellular Signaling Peptides and Proteins; C429018:NOD2 protein, human; D053473:Nod2 Signaling Adaptor Protein