Blau syndrome-associated mutations in exon 4 of the caspase activating recruitment domain 15 (CARD 15) gene are not found in ethnic Danes with sarcoidosis

TY - JOUR

T1 - Blau syndrome-associated mutations in exon 4 of the caspase activating recruitment domain 15 (CARD 15) gene are not found in ethnic Danes with sarcoidosis

AU - Milman, Nils

AU - Nielsen, Finn Cilius

AU - Hviid, Thomas Vauvert F

AU - Hansen, Thomas van Overeem

PY - 2007/12

Y1 - 2007/12

N2 - BACKGROUND: Distinct mutations of the caspase activating recruitment domain 15 (CARD15) gene (also known as nucleotide-binding oligomerisation domain protein 2) on chromosome 16q are associated with the chronic granulomatous disease called Blau syndrome. Sarcoidosis is a systemic granulomatous disease, which has features in common with Blau syndrome.AIM: The aim of this study was to evaluate whether ethnic Danes with sarcoidosis have CARD15 mutations associated with Blau syndrome.METHODS: Analysis of exon 4 of the CARD15 gene containing mutations associated with Blau syndrome was performed by polymerase chain reaction and sequencing of genomic DNA from 52 patients with histologically verified sarcoidosis.RESULTS: None of the patients had mutations in CARD15 associated with Blau syndrome. Eight other variations were found in exon 4: single nucleotide polymorphism (SNP)6 in 40% of the 104 alleles examined, SNP7 in 26%, c. 1833 C > T and SNP8 in 4%, c. 2107 C > T in 2%, and c. 931 C > T, c. 1292 C > T and c. 2377 G > A in 1%. One variation was found in intron 4 (IVS4 + 10 A > C) in 3% of the alleles. The frequencies of the variations in sarcoidosis patients were not statistically significant compared with frequencies in a control group of 103 healthy subjects. The course of disease was not significantly different in patients with or without variations in CARD15 or in the 46 patients with SNP6 and/or SNP7.CONCLUSIONS: Danish sarcoidosis patients have frequent variations in CARD15 exon 4, but do not present any mutation associated with Blau syndrome. The variations found had no influence on the course of disease.

AB - BACKGROUND: Distinct mutations of the caspase activating recruitment domain 15 (CARD15) gene (also known as nucleotide-binding oligomerisation domain protein 2) on chromosome 16q are associated with the chronic granulomatous disease called Blau syndrome. Sarcoidosis is a systemic granulomatous disease, which has features in common with Blau syndrome.AIM: The aim of this study was to evaluate whether ethnic Danes with sarcoidosis have CARD15 mutations associated with Blau syndrome.METHODS: Analysis of exon 4 of the CARD15 gene containing mutations associated with Blau syndrome was performed by polymerase chain reaction and sequencing of genomic DNA from 52 patients with histologically verified sarcoidosis.RESULTS: None of the patients had mutations in CARD15 associated with Blau syndrome. Eight other variations were found in exon 4: single nucleotide polymorphism (SNP)6 in 40% of the 104 alleles examined, SNP7 in 26%, c. 1833 C > T and SNP8 in 4%, c. 2107 C > T in 2%, and c. 931 C > T, c. 1292 C > T and c. 2377 G > A in 1%. One variation was found in intron 4 (IVS4 + 10 A > C) in 3% of the alleles. The frequencies of the variations in sarcoidosis patients were not statistically significant compared with frequencies in a control group of 103 healthy subjects. The course of disease was not significantly different in patients with or without variations in CARD15 or in the 46 patients with SNP6 and/or SNP7.CONCLUSIONS: Danish sarcoidosis patients have frequent variations in CARD15 exon 4, but do not present any mutation associated with Blau syndrome. The variations found had no influence on the course of disease.

KW - Adult

KW - Aged

KW - Alleles

KW - Denmark

KW - Exons

KW - Genetic Variation

KW - Granulomatous Disease, Chronic

KW - Humans

KW - Incidence

KW - Introns

KW - Male

KW - Middle Aged

KW - Mutation

KW - Nod2 Signaling Adaptor Protein

KW - Polymorphism, Single Nucleotide

KW - Sarcoidosis

KW - Syndrome

KW - Young Adult

KW - Journal Article

KW - Research Support, Non-U.S. Gov't

U2 - 10.1111/j.1752-699X.2007.00037.x

DO - 10.1111/j.1752-699X.2007.00037.x

M3 - Journal article

C2 - 20298285

SN - 1752-6981

VL - 1

SP - 74

EP - 79

JO - Clinical Respiratory Journal

JF - Clinical Respiratory Journal

IS - 2

ER -