PDF(Pubmed)
Abstract：
Primary immunodeficiencies are disorders of the immune system often caused by mutations of genes required for lymphocyte development. Phosphoinositide-3-kinase regulatory subunit 1 (PIK3R1) gene mutations are associated with SHORT syndrome, a rare multisystem disease. The name stands for Short stature, Hyperextensibility, Ocular depression, Rieger anomaly and Teething delay. Our case describes a child who presented with agammaglobulinemia with phenotypical features of SHORT syndrome. Upon further investigation, he was found to have a rare variant of the PIK3R1 gene mutation. This new mutation combines two distinct diseases with the same gene defect, which otherwise has been reported as two separate entities. The objective of this report is to identify a new gene mutation associated with SHORT syndrome along with agammaglobulinemia and to highlight the importance of recognizing the features of SHORT syndrome. We describe a nine-year-old male who presented with developmental delay and recurrent infections at the age of 12 months. Immunological evaluation revealed agammaglobulinemia and he has been scheduled for regular intravenous immunoglobulin replacement therapy. In view of characteristic syndromic physical features, speech and teething delay, we investigated further for the underlying genetic reason for agammaglobulinemia. The molecular analysis demonstrated a rare homozygous variant, c.244dup, in the PIK3R1 gene. This case reveals the association of the PIK3R1 gene mutation with agammaglobulinemia and SHORT syndrome. It further demonstrates the discovery of a new pathological variant of the gene. A detailed history and examination along with an immunological and genetic workup should be carried out for children with certain distinct phenotypical features. SHORT syndrome has specific characteristics that call for awareness and early recognition for prompt diagnosis and intervention. Emphasis is placed on genetic counseling as the disease is inherited in an autosomal recessive pattern, as demonstrated by molecular genetic studies.
摘要：
原发性免疫缺陷是通常由淋巴细胞发育所需的基因突变引起的免疫系统疾病。磷酸肌醇-3-激酶调节亚基1(PIK3R1)基因突变与SHORT综合征相关,一种罕见的多系统疾病。这个名字代表身材矮小，超扩展性,眼部抑郁,Rieger异常和牙齿延迟。我们的病例描述了一个患有无球蛋白血症并具有SHORT综合征表型特征的儿童。经进一步调查,他被发现有一个罕见的变异的PIK3R1基因突变。这种新的突变结合了两种不同的疾病，具有相同的基因缺陷，否则被报告为两个独立的实体。本报告的目的是确定与SHORT综合征和无丙种球蛋白血症相关的新基因突变，并强调认识SHORT综合征特征的重要性。我们描述了一名9岁的男性，他在12个月大时出现发育迟缓和反复感染。免疫学评估显示无丙种球蛋白血症，他已计划接受定期静脉注射免疫球蛋白替代疗法。鉴于特征性的综合征物理特征，说话和出牙延迟，我们进一步调查了无丙种球蛋白血症的潜在遗传原因。分子分析显示了一种罕见的纯合变体，c.244dup，在PIK3R1基因中。该病例揭示了PIK3R1基因突变与无丙种球蛋白血症和SHORT综合征的相关性。它进一步证明了该基因的新病理变体的发现。对于具有某些独特表型特征的儿童，应进行详细的病史和检查以及免疫和遗传检查。SHORT综合征具有特定的特征，需要意识和早期识别以及时诊断和干预。重点放在遗传咨询，因为该疾病以常染色体隐性遗传模式遗传，正如分子遗传学研究所证明的那样。
