Blau syndrome is an autosomal dominant rare disease caused by mutations in NOD2 gene. Less than 200 patients published with Blau Syndrome Worldwide. We reported a 41-year old female Turkish patient diagnosed as Blau syndrome. Granulomatous dermatitis and severe headache, as well as recurrent chest and pelvic pain have been present since she was 8 years old. Arthritis started when she was teenage, hypertension diagnosed when she was 20 and other symptoms also occurred during the lifetime (severe preeclampsia, ischemic stroke, recurrent hemiparesis, recurrent-transient-vision-loss and renal-artery-stenosis). Genomic DNA was isolated from peripheral blood and 12 genes sequenced in Autoinflammatory panel on IonTorrent-S5-NGS platform with Parseq-VariFind™AIPassay. NGS analysis showed 107 variants in in the index case, mainly benign with no strong association with Blau syndrome. Additionally, we identified one very rare missense mutation in NOD2 gene (c2803G>A, p.Val935Met) and in silico assessment of the mutation indicated possible pathogenic significance and strong association with Blau syndrome. In addition, we analyzed family members of the index case and identified the same mutation in NOD2 gene. The segregation analysis shows the presence of the same mutant allele in NOD2 gene in the index case affected sister, as well as in her son with arthralgia, while in her non affecter brother we didn't detect the Val935Met mutation in NOD2 gene. Blau Syndrome is known as a very rare disease, mainly caused by mutations in NOD2 gene. Missense mutation diagnosed in our case could be responsible for the phenotype of the index case. Our results indicate the importance of NGS testing and its major role in the detection of rare mutations that may responsible for the onset of autoinflammatory disorders.

中文翻译：

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Blau综合征的NOD2基因第9外显子罕见突变。

布劳综合征是由NOD2基因突变引起的常染色体显性遗传性罕见病。全世界不到200例布劳综合症患者。我们报道了一名41岁的土耳其女性患者，被诊断为布劳综合征。自8岁起就出现肉芽肿性皮炎和严重头痛，以及反复出现的胸部和骨盆疼痛。关节炎从十几岁开始，一到二十岁就被诊断出高血压，一生中也出现了其他症状（严重的先兆子痫，缺血性中风，反复偏瘫，反复短暂性视力减退和肾动脉狭窄）。从外周血中分离基因组DNA，并在IonTorrent-S5-NGS平台上的自动炎症面板中使用Parseq-VariFind™AIPassay对12个基因进行测序。NGS分析显示索引案例中有107个变体，主要表现为良性，与布劳综合症无明显关联。此外，我们在NOD2基因中发现了一个非常罕见的错义突变（c2803G> A，p.Val935Met），并且对该突变的计算机评估表明其可能具有致病性，并与Blau综合征密切相关。此外，我们分析了索引病例的家庭成员，并确定了NOD2基因中的相同突变。分离分析显示，在受索引病例影响的姐妹以及患有关节痛的儿子中，NOD2基因中存在相同的突变等位基因，而在非患病兄弟中，我们未在NOD2基因中检测到Val935Met突变。布劳综合症是一种非常罕见的疾病，主要由NOD2基因突变引起。在我们的病例中诊断出的错义突变可能是导致索引病例表型的原因。