SOPH syndrome in three affected individuals showing similarities with progeroid cutis laxa conditions in early infancy
SOPH syndrome in three affected individuals showing similarities with progeroid cutis laxa conditions in early infancy
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DOI：
10.1038/s10038-019-0602-8
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发表时间：
2019-07-01
影响因子：
3.5
通讯作者：
Kornak, Uwe
中科院分区：
文献类型：
--
作者：
Fischer-Zirnsak, Bjoern;Koenig, Rainer;Kornak, Uwe
患有 2B 型和 3 型常染色体隐性皮肤松弛症的个体通常表现出半透明皮肤、可见静脉和异常弹性纤维、宫内和/或产后生长受限以及典型的三角形面部形态。在这里，我们描述了三个无关的个体，他们被怀疑患有这种皮肤松弛综合症，特别是在电子显微镜显示其中一个人的真皮弹性纤维不成熟且密度较低之后。然而，其中一名儿童还表现出视神经萎缩和两名低丙种球蛋白血症。所有患者在发热期间均出现肝酶升高和急性肝功能衰竭，导致其中两人过早死亡。唯一幸存的患者接受了免疫球蛋白治疗。通过外显子组测序，我们发现了 NBAS 的突变，编码参与高尔基体到内质网运输的蛋白质。 NBAS 缺乏会导致多种罕见疾病，从孤立的复发性急性肝衰竭到主要以身材矮小、视神经萎缩和 Pelger-Huet 异常 (SOPH) 为特征的多系统疾病。由于我们随后在其中两名患者中验证了 PelgerHuet 异常，因此 SOPH 综合征的诊断得到明确证实。我们的数据表明，SOPH 综合征可被视为婴儿早期早衰样皮肤松弛的鉴别诊断，并且低丙种球蛋白血症的治疗可能与预后高度相关。
Individuals affected with autosomal recessive cutis laxa type 2B and 3 usually show translucent skin with visible veins and abnormal elastic fibers, intrauterine and/or postnatal growth restriction and a typical triangular facial gestalt. Here we describe three unrelated individuals in whom such a cutis laxa syndrome was suspected, especially after electron microscopy revealed immature and less dense dermal elastic fibers in one of them. However, one of these children also displayed optic atrophy and two hypogammaglobulinemia. All had elevated liver enzymes and acute liver failure during febrile episodes leading to early demise in two of them. The only surviving patient had been treated with immunoglobulins. Through exome sequencing we identified mutations in NBAS, coding for a protein involved in Golgi-to-ER transport. NBAS deficiency causes several rare conditions ranging from isolated recurrent acute liver failure to a multisystem disorder mainly characterized by short stature, optic nerve atrophy and Pelger-Huet anomaly (SOPH). Since we subsequently verified PelgerHuet anomaly in two of the patients the diagnosis SOPH syndrome was unequivocally proven. Our data show that SOPH syndrome can be regarded as a differential diagnosis for the progeroid forms of cutis laxa in early infancy and that possibly treatment of the hypogammaglobulinemia can be of high relevance for the prognosis.