CARD15 mutations in familial granulomatosis syndromes: A study of the original Blau syndrome kindred and other families with large-vessel arteritis and cranial neuropathy

Xiaoju Wang, Helena Kuivaniemi, Gina Bonavita, Lysette Mutkus, Ulrike Mau, Edward Blau, Naohiro Inohara, Gabriel Nunez, Gerard Tromp, Charlene J. Williams

Research output: Contribution to journalArticlepeer-review

104 Scopus citations

Abstract

Objective. To analyze the CARD15 gene in families with heritable multi-organ granulomatoses, including the original Blau syndrome kindred as well as other families with related granulomatous conditions. Methods. Linkage mapping was performed in 10 families. Observed recombination events were used to exclude regions centromeric or telomeric to 16q12.1, and the Blau gene critical region was refined to <3 cM, corresponding to a physical distance of 3.5 megabasepairs. Based on its known biochemical function, CARD15 was analyzed as a positional candidate for the Blau syndrome susceptibility gene, by direct DNA sequencing. Results. These studies resulted in the identification, in 5 of the families, of 2 sequence variants at position 334 of the gene product (R334W and R334Q). Affected family members from the original Blau syndrome kindred were heterozygous for the R334W missense mutation; mutations at the same position were also observed in several unrelated Blau syndrome families, some of whose phenotypes included large-vessel arteritis and cranial neuropathy. The missense mutations segregated with the disease phenotype in the families, and were not seen in 208 control alleles. Conclusion. These findings demonstrate that CARD15 is an important susceptibility gene for Blau syndrome and for other familial granulomatoses that display phenotypic traits beyond those of classic Blau syndrome.

Original languageEnglish (US)
Pages (from-to)3041-3045
Number of pages5
JournalArthritis and Rheumatism
Volume46
Issue number11
DOIs
StatePublished - Nov 1 2002

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Rheumatology
  • Immunology
  • Pharmacology (medical)

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