Further delineation of the phenotype of severe congenital neutropenia type 4 due to mutations in G6PC3
Further delineation of the phenotype of severe congenital neutropenia type 4 due to mutations in G6PC3
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DOI：
10.1038/ejhg.2010.136
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发表时间：
2011-01-01
影响因子：
5.2
通讯作者：
Shalev, Stavit
中科院分区：
文献类型：
--
作者：
Banka, Siddharth;Chervinsky, Elena;Shalev, Stavit
重度先天性中性粒细胞减少4型（SCN4）是一种常染色体隐性遗传病，最近在G6PC3中发现了致病突变。迄今为止，文献中只有三篇报道描述了G6PC3基因突变的SCN4患者。我们报告了4个患有SCN4的个体，他们属于一个大的近亲。我们提供了一个非血液学特征的条件的概述，重点是成人表型，这在以前没有详细描述。我们发现SCN4患者的浅表静脉改变可在成年期发展为静脉曲张和静脉溃疡。我们回顾了与SCN4相关的先天性异常的范围。我们证明，第二房间隔缺损，动脉导管未闭和瓣膜缺损是SCN4中最常见的心脏异常。与1型糖原蓄积性疾病相似，我们认为产前发育不良、轻度至中度学习障碍、原发性肺动脉高压、青春期延迟或不完全、甲状腺功能减退和畸形可能是该综合征的特征。我们还建议监测血脂异常，以及患者的肾脏和肝脏功能。SCN4表型的描述可能有助于适当的治疗和管理，并为这种多系统疾病的发病机制提供进一步的见解。欧洲人类遗传学杂志（2011）19,18 -22；doi: 10.1038 / ejhg.2010.136;2010年8月18日在线发布
Severe congenital neutropenia type 4 (SCN4) is an autosomal recessive condition, which was defined recently with identification of the causative mutations in G6PC3. To date there are only three reports in the literature describing patients with SCN4 with mutations in the G6PC3 gene. We report four individuals with SCN4 who belong to a single large consanguineous kindred. We provide an overview of the non-haematological features of the condition with a focus on the adult phenotype, which has not been previously described in detail. We show that the superficial venous changes seen in SCN4 patients can develop into varicose veins and venous ulcers in adulthood. We review the range of congenital anomalies associated with SCN4. We demonstrate that secundum atrial septal defect, patent ductus arteriosus and valvular defects are the most frequent cardiac anomalies in SCN4. Drawing parallels with type 1 glycogen storage disease, we propose that poor growth of prenatal onset, mild-to-moderate learning disability, primary pulmonary hypertension, delayed or incomplete puberty, hypothyroidism and dysmorphism likely represent features of this syndrome. We also suggest monitoring for lipid anomalies, and kidney and liver function in affected patients. Delineation of the SCN4 phenotype may help in appropriate treatment and management and provide further insights into the pathogenesis of this multisystem disease. European Journal of Human Genetics (2011) 19, 18-22; doi:10.1038/ejhg.2010.136; published online 18 August 2010