Purchase this article with an account.
TM Doyle, KC Rust, D Dinulescu, JR Smith, JT Rosenbaum, TM Martin; Sequencing of the IBD1 Gene, CARD15, in Sarcoidosis Patients with and without Uveitis . Invest. Ophthalmol. Vis. Sci. 2002;43(13):4249.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
Purpose: Mutations in CARD15 (IBD1, NOD2) are responsible for a rare, autosomal-dominant syndrome: familial juvenile systemic granulomatosis (Blau syndrome). This syndrome can be mistakenly diagnosed as sarcoidosis as patients share the features of uveitis, arthritis and dermatitis with granuloma formation. Approximately 25% of patients with another granulomatous disease, Crohn's disease, are homozygous for mutations in CARD15 distinct from the Blau mutations. CARD15 contains several functional domains including 2 caspase recruitment domains (CARD), a nucleotide binding domain (site of the Blau mutations) and a leucine rich repeat region (site of the Crohn's mutations). We sought to determine if mutations in CARD15 occurred in patients with a third granulomatous disease, sarcoidosis, particularly those with the complication of uveitis. Methods: Patients with sarcoidosis submitted a blood sample after giving permission by informed consent. Patients with sarcoidosis-associated uveitis (n=12, 7 female, 5 male) and patients with sarcoidosis but not uveitis (n=12, 11 female, 1 male) were analyzed. The age range for each group was 34-74 years (with uveitis) and 40-66 years (without uveitis). The majority of patients in both groups were Caucasian. DNA was extracted from white blood cells by standard techniques. Each of the 12 exons of the CARD15 gene were amplified by PCR (exons 5 and 6 were amplified together). The PCR products were gel purified and subjected to sequencing. Sequencing was performed by the Portland VA Medical Center Molecular Biology Core Lab on an ABI 377 automated fluorescence DNA sequencer. Results: A DNA sequence polymorphism in exon 9 was observed in 3 out of 12 patients with uveitis and in none of the patients without uveitis. This polymorphism changes a "c" to a "t" and corresponds to position 2968 in the mRNA sequence. This results in a conservative amino acid change (valine to isoleucine) at position 955. All 3 patients with this change were heterozygous for the polymorphism. Conclusion: The polymorphism described here is in the leucine-rich repeat domain of the protein, the same domain where mutations have been found to be associated with Crohn's disease. However, this particular polymorphism (V955I) is not reported to be associated with Crohn's disease. It is possible that mutations in the CARD15 gene may play a role in the development of uveitis as a complication of sarcoidosis.
This PDF is available to Subscribers Only