PDF(Pubmed)
Abstract：
The aim of this study was to describe the clinical and molecular genetic findings in seven individuals from three unrelated families with Blau syndrome. A complex ophthalmic and general health examination including diagnostic imaging was performed. The NOD2 mutational hot spot located in exon 4 was Sanger sequenced in all three probands. Two individuals also underwent autoinflammatory disorder gene panel screening, and in one subject, exome sequencing was performed. Blau syndrome presenting as uveitis, skin rush or arthritis was diagnosed in four cases from three families. In two individuals from one family, only camptodactyly was noted, while another member had camptodactyly in combination with non-active uveitis and angioid streaks. One proband developed two attacks of meningoencephalitis attributed to presumed neurosarcoidosis, which is a rare finding in Blau syndrome. The probands from families 1 and 2 carried pathogenic variants in NOD2 (NM_022162.3): c.1001G>A p.(Arg334Gln) and c.1000C>T p.(Arg334Trp), respectively. In family 3, two variants of unknown significance in a heterozygous state were found: c.1412G>T p.(Arg471Leu) in NOD2 and c.928C>T p.(Arg310*) in NLRC4 (NM_001199139.1). In conclusion, Blau syndrome is a phenotypically highly variable, and there is a need to raise awareness about all clinical manifestations, including neurosarcoidosis. Variants of unknown significance pose a significant challenge regarding their contribution to etiopathogenesis of autoinflammatory diseases.
摘要：
这项研究的目的是描述来自三个无关的Blau综合征家庭的七个个体的临床和分子遗传学发现。进行了复杂的眼科和一般健康检查，包括诊断成像。在所有三个先证中对位于外显子4中的NOD2突变热点进行了Sanger测序。两名个体还接受了自身炎症性疾病基因小组筛查，在一个主题中，进行外显子组测序.布劳综合征表现为葡萄膜炎，来自三个家庭的四例患者被诊断出皮肤急流或关节炎。在一个家庭的两个人中，只有Camptodactyly被注意到，而另一名成员患有camptodyly并伴有非活动性葡萄膜炎和血管样条纹。一个先证者发展了两次脑膜脑炎的发作，归因于假定的神经结节病，这在布劳综合症中是罕见的发现。来自家族1和2的先证者在NOD2（NM_022162.3）中携带致病性变体：c.1001G>Ap。（Arg334Gln）和c.1000C>Tp。（Arg334Trp），分别。在家族3中，在杂合状态下发现了两个未知意义的变体：NOD2中c.1412G>Tp。（Arg471Leu）和NLRC4（NM_001199139.1）中c.928C>Tp。（Arg310*）。总之,布劳综合征是一种表型高度可变的，有必要提高对所有临床表现的认识，包括神经结节病.意义未知的变体对自身炎性疾病的病因构成了重大挑战。
