背景:ABCC8变异体可通过激活或失活基因表达引起高胰岛素血症。本研究使用靶向外显子测序来研究中国高胰岛素血症性低血糖(HH)患者ABCC8的遗传变异和相关表型特征。
方法:我们招募了8名中国HH患儿,并分析了他们的临床特征,实验室结果,和遗传变异。
结果:患者的就诊年龄范围从新生儿到0.6岁,诊断年龄从1个月到5岁,平均1.3±0.7年。在这些患者中,三个人出现癫痫发作,和五个低血糖。一名患者(患者7)也患有小头畸形。8例患者均表现为ABCC8异常,包括六个错义突变(c。2521C>G,c.3784G>A,c.4478G>A,c.4532T>C,c.2669T>C,和c。331G>A),两个缺失-插入突变(c.3126_3129delinsTCandc.3124_3126delins13),和一个剪接突变(c.1332+2T>C)。其中两个突变(c。3126_3129delinsTC和c。4532T>C)是新颖的。六种变化是父系的,两个是母亲,一个是从头。三名患者对二氮嗪有反应,一名患者对奥曲肽治疗有反应。所有患者均有二氮嗪戒断。两名患者(患者3和7)对二氮嗪和奥曲肽均无反应,并且智力低下。
结论:基因分析可以帮助分类,治疗,HH患儿的预后。在这项研究中,ABCC8基因中7个已知变异体和2个新变异体的鉴定进一步丰富了该基因的变异谱。
BACKGROUND: ABCC8 variants can cause hyperinsulinemia by activating or deactivating gene expression. This study used targeted exon sequencing to investigate genetic variants of ABCC8 and the associated phenotypic features in Chinese patients with hyperinsulinemic hypoglycemia (HH).
METHODS: We enrolled eight Chinese children with HH and analyzed their clinical characteristics, laboratory results, and genetic variations.
RESULTS: The age at presentation among the patients ranged from neonates to 0.6 years old, and the age at diagnosis ranged from 1 month to 5 years, with an average of 1.3 ± 0.7 years. Among these patients, three presented with seizures, and five with hypoglycemia. One patient (Patient 7) also had microcephaly. All eight patients exhibited ABCC8 abnormalities, including six missense mutations (c. 2521 C > G, c. 3784G > A, c. 4478G > A, c. 4532T > C, c. 2669T > C, and c. 331G > A), two deletion-insertion mutations (c. 3126_3129delinsTC and c. 3124_3126delins13), and one splicing mutation (c. 1332 + 2T > C). Two of these mutations (c. 3126_3129delinsTC and c. 4532T > C) are novel. Six variations were paternal, two were maternal, and one was de novo. Three patients responded to diazoxide and one patient responded to octreotide treatment. All there patients had diazoxide withdrawal with age. Two patients (patients 3 and 7) were unresponsive to both diazoxide and octreotide and had mental retardation.
CONCLUSIONS: Gene analysis can aid in the classification, treatment, and prognosis of children with HH. In this study, the identification of seven known and two novel variants in the ABCC8 gene further enriched the variation spectrum of the gene.