王珊, 刘盈, 徐子刚, 王召阳, 焦磊, 梁源, 徐哲, 马琳. 常染色体显性及隐性遗传高免疫球蛋白E综合征临床特征及基因分析[J]. 罕见病研究, 2022, 1(3): 268-277. DOI: 10.12376/j.issn.2097-0501.2022.03.007
引用本文: 王珊, 刘盈, 徐子刚, 王召阳, 焦磊, 梁源, 徐哲, 马琳. 常染色体显性及隐性遗传高免疫球蛋白E综合征临床特征及基因分析[J]. 罕见病研究, 2022, 1(3): 268-277. DOI: 10.12376/j.issn.2097-0501.2022.03.007
WANG Shan, LIU Ying, XU Zigang, WANG Zhaoyang, JIAO Lei, LIANG Yuan, XU Zhe, MA Lin. Clinical Features and Genetic Analysis of Autosomal Dominant and Recessive Hyperimmunoglobulin E Syndrome[J]. Journal of Rare Diseases, 2022, 1(3): 268-277. DOI: 10.12376/j.issn.2097-0501.2022.03.007
Citation: WANG Shan, LIU Ying, XU Zigang, WANG Zhaoyang, JIAO Lei, LIANG Yuan, XU Zhe, MA Lin. Clinical Features and Genetic Analysis of Autosomal Dominant and Recessive Hyperimmunoglobulin E Syndrome[J]. Journal of Rare Diseases, 2022, 1(3): 268-277. DOI: 10.12376/j.issn.2097-0501.2022.03.007

常染色体显性及隐性遗传高免疫球蛋白E综合征临床特征及基因分析

Clinical Features and Genetic Analysis of Autosomal Dominant and Recessive Hyperimmunoglobulin E Syndrome

  • 摘要:
      目的  总结常染色体显性及隐性遗传高免疫球蛋白E综合征(HIES)患儿的临床特征及基因分析。
      方法  收集于2013年1月至2021年12月在首都医科大学附属北京儿童医院皮肤科收治的经临床及基因共同确诊为HIES患儿,归纳一般资料并分析其临床特征和基因型特点,比较常染色体显性遗传HIES(AD-HIES)和常染色体隐性遗传HIES(AR-HIES)临床特点的异同。
      结果  共收集确诊HIES患儿7例,其中AD-HIES 3例,AR-HIES 4例。男4例,女3例。所有患儿均存在反复发作的顽固性湿疹样皮疹、反复皮肤及肺部感染,以及血清IgE和嗜酸性粒细胞水平升高。AD-HIES与AR-HIES的不同点主要包括:3例AD-HIES患儿皮肤感染均以细菌感染为主要表现(如脓肿、脓疱疮),而4例AR-HIES患儿皮肤均以严重的病毒感染为主要表现(如寻常疣、传染性软疣);3例AD-HIES患儿均存在不同种类的肺部实质改变(如肺大疱、肺囊肿、肺不张),而4例AR-HIES患儿肺部均无类似改变;AR-HIES患儿中3/4存在过敏性疾病(包括哮喘、食物过敏等),而AD-HIES患儿均无过敏性疾病报道;免疫系统外表现方面,AD-HIES更易见鼻梁扁平、高腭弓等特殊面容,AR-HIES中有肿瘤发生情况而AD-HIES尚未见。AD-HIES主要由STAT3基因突变引起,AR-HIES主要由DOCK8基因突变引起,其中两例患儿分别存在DOCK8基因的c.1798-2A>T和c.874G>A为新发突变位点。
      结论  对于临床表现为顽固性湿疹样皮疹、反复感染,伴血清IgE水平显著升高的患儿,需寻找早期HIES疑诊线索,尽早进行基因检测明确诊断及分类,以更好地长期管理,改善生存预后。

     

    Abstract:
      Objective  To summarize the clinical and genetic features of children with autosomal dominant and recessive hyperimmunoglobulin E syndrome (HIES).
      Methods  HIES patients were studied at the dermatology department of Beijing Children's Hospital, Capital Medical University were collected, from January 2013 to December 2021, diagnosed by both clinical manifestation and genetic assessment. The general data were summarized, the clinical and genetic characteristics were analyzed, and the similarities and differences between autosomal dominant HIES (AD-HIES) and autosomal recessive HIES (AR-HIES) were compared.
      Results  A total of 7 children with HIES were studied, including 3 cases of AD-HIES and 4 cases of AR-HIES. There were 4 males and 3 females. All children had recurrent eczema-like lesions, recurrent skin and pulmonary infections, and elevated serum IgE and eosinophil levels. The differences between AD-HIES and AR-HIES mainly include: the main cutaneous infection in 3 children with AD-HIES were bacterial infections (such as abscess and impetigo), while in 4 children with AR-HIES, cutaneous infections were mostly severe viral infection (such as verruca vulgaris and molluscum contagiosum). There were pulmonary parenchymal changes (such as pneumatoceles, cyst and atelectasis) in 3 children with AD-HIES, whilst there were no similar changes in the lungs of 4 children with AR-HIES; 75% of children with AR-HIES had allergic diseases (including asthma and food allergy), while there were no reports of allergic diseases in children with AD-HIES. As for manifestations outside of immune system, AD-HIES was more likely to appear facial dysmorphism(such a broad nasal bridge and a high-arched palate). Furthermore, the incidence of tumor in AR-HIES was higher than that in AD-HIES. AD-HIES was mainly caused by the mutation of STAT3 gene, and AR-HIES was mainly caused by the mutation of DOCK8 gene. We reported two new mutation sites of DOCK8 gene c.1798-2A > T and c.874G > A in two cases, respectively.
      Conclusions  For children with clinical manifestations of recurrent eczema-like lesions, repeated infection and significant increase in serum IgE levels, HIES should be suspected, and genetic screening should be carried out to make definite diagnosis and classification, to achieve better long-term management and improve prognosis.

     

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