Selcuk University Faculty of Medicine, Department of Pediatrics, Division of Pediatric Infectious Diseases.
Selcuk University Faculty of Medicine, Department of Ophthalmology.
Blood Coagul Fibrinolysis. 2023 Oct 1;34(7):456-461. doi: 10.1097/MBC.0000000000001246. Epub 2023 Jul 27.
Ligneous conjunctivitis (LC) is a chronic conjunctivitis characterized by recurrent, firm, fibrin-rich, woody pseudomembranes on the palpebral conjunctiva. It is an ultrarare autosomal recessive disease associated with congenital plasminogen (PLG) deficiency due to mutations in the PLG gene (6q26). Immunoglobulin G4-related disease (IgG4-RD) is an idiopathic, systemic fibroinflammatory disease characterized by elevated serum IgG4 concentration and tissue infiltration of IgG4-positive plasma cells leading to organ enlargement, fibrosis and damage.
A 7-year-old girl with LC was hospitalized for recurrent pancreatitis and diagnosed as IgG4-RD. PLG activity level was 15% (normal range 55-145%). Co-segregation analysis indicated that the patient was homozygous for the c. NG_016200.1(NM_000301.5):c.1465 T>C mutation in PLG gene. c. NG_016200.1(NM_000301.5):c.1465 T>C PLG variant was found to be heterozygous by NGS analysis in both parents. She also had plasminogen activator inhibitor - 1 (PAI-1) NG_013213.1(NM_000602.5):c.-816A>G (4G/4G) homozygous polymorphism and a heterozygote NG_001333.2 (NM_002769.5):c.292_293insC mutation in the serine protease 1 (PRSS-1) gene. However, heterozygous PRSS-1NG_001333.2 (NM_002769.5):c.292_293insC variant was found in the mother of the patient. All detected variants are currently considered as a variant of uncertain (or unknown) significance (VUS) according to the American College of Medical Genetics and Genomics (ACMG) classification. Oral steroid, oral azathioprine, topical fresh frozen plasma, topical heparin, topical steroid and topical cyclosporine were given. After 3 years of follow-up, IgG4-RD is under partial remission and no pseudomembranes.
She is the second case had both LC and IgG4-RD. We identified a NG_016200.1(NM_000301.5):c.1465 T>C novel homozygous mutation in PLG gene and a PAI-1 NG_016200.1(NM_000301.5):c.1465 T>C (4G/4G) homozygous polymorphism, which has been reported as a risk factor for thrombotic events.
树突状结膜炎（LC）是一种慢性结膜炎，其特征为反复发作、坚硬、富含纤维蛋白的木样伪膜，位于睑结膜上。它是一种超罕见的常染色体隐性疾病，与先天性纤溶酶原（PLG）缺乏有关，由 PLG 基因（6q26）突变引起。免疫球蛋白 G4 相关疾病（IgG4-RD）是一种特发性系统性纤维炎症性疾病，其特征为血清 IgG4 浓度升高，组织中 IgG4 阳性浆细胞浸润导致器官肿大、纤维化和损伤。
一名 7 岁女孩因 LC 反复发作胰腺炎住院，被诊断为 IgG4-RD。PLG 活性水平为 15%（正常范围 55-145%）。共分离分析表明，该患者 PLG 基因杂合子 c. NG_016200.1（NM_000301.5）：c.1465 T>C 突变。通过 NGS 分析在父母双方均发现 PLG 变体 c. NG_016200.1（NM_000301.5）：c.1465 T>C 为杂合子。该患者还存在纤溶酶原激活物抑制剂-1（PAI-1）NG_013213.1（NM_000602.5）：c.-816A>G（4G/4G）纯合子多态性和丝氨酸蛋白酶 1（PRSS-1）基因的杂合子 NG_001333.2（NM_002769.5）：c.292_293insC 突变。然而，在患者的母亲中发现了杂合子 PRSS-1NG_001333.2（NM_002769.5）：c.292_293insC 变体。所有检测到的变体根据美国医学遗传学与基因组学学院（ACMG）分类目前被认为是意义不明（或未知）的变体（VUS）。给予口服类固醇、口服硫唑嘌呤、局部新鲜冷冻血浆、局部肝素、局部类固醇和局部环孢素。经过 3 年的随访，IgG4-RD 部分缓解，无伪膜。
这是第二例同时患有 LC 和 IgG4-RD 的病例。我们在 PLG 基因中发现了一个新的 c. NG_016200.1（NM_000301.5）：c.1465 T>C 纯合突变，以及一个 PAI-1 NG_016200.1（NM_000301.5）：c.1465 T>C（4G/4G）纯合多态性，据报道这是血栓事件的危险因素。
