Ocular manifestations in Blau syndrome associated with a CARD15/Nod2 mutation

Kurokawa, Toru; Kikuchi, Takanobu; Ohta, Kouichi; Imai, Hisanori; Yoshimura, Nagahisa

doi:10.1016/s0161-6420(03)00717-6

Cited by 79 publications

(53 citation statements)

References 10 publications

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“…6,7 While mutations in LRRs are reportedly associated with Crohn disease (CD) and psoriatic arthritis, [8][9][10] 3 types of missense point mutations in the NOD, 1000CϾT (R334W in amino acid change), 1001GϾA (R334Q), and 1405CϾT (L469F), have been discovered in BS families. 5,11,12 It has been discussed since the first report of BS whether EOS and BS are the same diseases. 13 However, no direct evidence of their common origin has been shown and confusion still remains.…”

Section: Introductionmentioning

confidence: 99%

Early-onset sarcoidosis and CARD15 mutations with constitutive nuclear factor- B activation: common genetic etiology with Blau syndrome

Kanazawa

Okafuji

Kambe

et al. 2004

Blood

460

345

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Early-onset sarcoidosis (EOS) and inheritable Blau syndrome (BS) share characteristic clinical features of juvenile-onset systemic granulomatosis syndrome that mainly affects skin, joints, and eyes. However, no direct evidence has been shown for the possible common origin of these 2 diseases. Recent discovery of CARD15 mutations in BS families encouraged us to investigate similar CARD15 mutations in EOS patients. Among 10 EOS cases retrospectively collected in Japan, heterozygous missense mutations were found in 9 cases; 4 showed a 1000C>T (R334W in amino acid change) that has been reported in BS, 4 showed novel 1487A>T (H496L) , IntroductionSarcoidosis is a multiorganic inflammatory disease with unknown etiology, characterized by the histologic features of noncaseating epithelioid granulomas. In childhood, 2 distinct types of sarcoidosis have been described. 1 Usually the disease is detected in older children by chest radiography and the clinical manifestations are characterized by a classical triad of lung, lymph node, and eye involvement, similar to those in adults. In contrast, early-onset sarcoidosis (EOS), which usually appears in those younger than 4 years of age, is quite rare and has a distinct triad of skin, joint, and eye disorders, without apparent pulmonary involvement. Compared with an asymptomatic and sometimes naturally disappearing course of the disease in older children, EOS is progressive and in many cases causes severe complications, such as blindness, joint destruction, and visceral involvement. 2 Blau syndrome (BS), also showing early-onset granulomatous arthritis, uveitis, and skin rash, is a rare familial disease transmitted in an autosomal dominant manner. 3 By linkage analysis, the responsible locus for BS was mapped to chromosome 16,4 in which CARD15 has recently been identified as the susceptibility gene. 5 CARD15 (NOD2) is a member of the growing family of nucleotide-binding oligomerization domain (NOD) proteins and composed of 2 amino-terminal caspase recruitment domains (CARDs), one NOD, and carboxy-terminal leucinerich repeats (LRRs). 6,7 While mutations in LRRs are reportedly associated with Crohn disease (CD) and psoriatic arthritis, 8-10 3 types of missense point mutations in the NOD, 1000CϾT (R334W in amino acid change), 1001GϾA (R334Q), and 1405CϾT (L469F), have been discovered in BS families. 5,11,12 It has been discussed since the first report of BS whether EOS and BS are the same diseases. 13 However, no direct evidence of their common origin has been shown and confusion still remains. 14 In the first paper describing genetic abnormalities in BS, the authors recognized no CARD15 mutation in 2 EOS patients and therefore proposed a different etiology of BS and EOS. 5 However, we have recently described a sporadic case of systemic granulomatosis syndrome with clinical features of EOS that showed the same CARD15 mutation as detected in BS. 15 In this report, therefore, we retrospectively collected Japanese EOS cases and searched for CARD15 mutations, to further evaluate the re...

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Section: Introductionmentioning

confidence: 99%

Early-onset sarcoidosis and CARD15 mutations with constitutive nuclear factor- B activation: common genetic etiology with Blau syndrome

Kanazawa

Okafuji

Kambe

et al. 2004

Blood

460

345

View full text Add to dashboard Cite

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“…7,12,13 Granulomas were absent in this study sample, as described in a previous report. 9 This observation was also not unexpected, as the patient had been treated for a prolonged period with immunosuppressive medications and had long-standing disease quiescence.…”

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confidence: 78%

“…8 Most commonly, patients develop a granulomatous panuveitis and some degree of its sequelae, including band keratopathy, anterior and posterior synechiae, iris bombe, secondary glaucoma, cataract, cystoid macular edema, chorioretinal lesions or scarring, and retinal detachment. 9 Pathologic investigation of ocular fluids and tissues in Blau patients has been limited. 10 Nonspecific iris inflammation and absence of multinucleated giant and epithelioid cells was described in one iridectomy specimen.…”

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confidence: 99%

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Immunohistochemical Evidence of Specific Iris Involvement in Blau Syndrome

Paparizos

Goldstein

Bouhenni

et al. 2012

Ocular Immunology and Inflammation

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“…[1][2][3]59 Anterior or panuveitis is the most common ocular manifestation of EOS/BS and may present with eye pain, photophobia, and blurred vision. 14,28,38 Granulomatous inflammation can also involve the conjunctiva, lacrimal glands, retina, and optic nerve, and ocular complications include cataracts and glaucoma. 28 Because early ocular disease is often asymptomatic and its onset can be delayed, slitlamp examination should be performed on a regular basis.…”

Section: Commentmentioning

confidence: 99%