Identification of a Novel Mutation in Carboxyl Ester Lipase Gene in a Patient with MODY-like Diabetes
Identification of a Novel Mutation in Carboxyl Ester Lipase Gene in a Patient with MODY-like Diabetes
复制标题
DOI：
10.1620/tjem.256.37
复制
发表时间：
2022-01-01
影响因子：
2.2
通讯作者：
Kurahashi, Hiroki
中科院分区：
文献类型：
--
作者：
Kondoh, Tomomi;Nakajima, Yoko;Kurahashi, Hiroki
青年成熟型糖尿病（MODY）是一种糖尿病，其特点是常染色体显性遗传，发病早，缺乏胰腺自身免疫标记物。在14个基因中发现了引起MODY8的突变，羧基酯脂肪酶（CEL）与MODY8有关。我们报道了一例日本MODY患者，其细胞外显子2存在异质突变（NM_001807.4:c.146_147delCT; NP_001798.2:p.Ser49CysfsTer52）。13岁女孩首次出现糖尿病酮症酸中毒，内源性胰岛素分泌差。但患者胰岛素分泌在胰岛素治疗开始2个月后明显恢复，此后2年无需进一步治疗。患者15岁时再次发生糖尿病酮症酸中毒，此时胰岛素分泌再次变差。从那时起，这位现年18岁的患者一直在接受持续的胰岛素治疗。她胰岛素分泌能力的大幅波动使我们怀疑是MODY。携带CEL基因最后外显子可变数目串联重复序列突变的MODY8患者通常表现为胰腺外分泌功能障碍。然而，在本病例中，其特征是过早终止，没有涉及外分泌功能障碍，潜在地证明了基因型-表型相关。
Maturity-onset diabetes of the young (MODY) is a form of diabetes mellitus characterized by autosomal dominant inheritance, early onset, and the absence of pancreatic autoimmune markers. MODY-causing mutations have been identified in 14 genes, and carboxyl ester lipase (CEL) has been implicated in MODY8. We report a Japanese patient with MODY who harbored a heterogeneous mutation in CEL exon 2 (NM_001807.4:c.146_147delCT; NP_001798.2:p.Ser49CysfsTer52). A 13-year-old girl experienced her first episode of diabetic ketoacidosis, during which her endogenous insulin secretion was poor. However, her insulin secretion had apparently recovered 2 months after the commencement of insulin treatment, and no further treatment was required for the following 2 years. Diabetic ketoacidosis recurred when the patient was 15 years old, when her insulin secretion was again poor. Since that time, the patient, who is now 18 years old, has been undergoing continuous insulin treatment. The large fluctuations in her insulin secretory capacity led us to suspect MODY. MODY8 patients that carry a mutation in the variable number of tandem repeats in the last exon of the CEL gene typically show pancreatic exocrine dysfunction. However, in the present case, which features premature termination, there is no involvement of exocrine dysfunction, potentially demonstrating a genotype-phenotype correlation.