BCHE基因复合杂合变异致丁酰胆碱酯酶缺乏症临床特征和遗传分析

doi:10.3969/j.issn.1673-8640.2022.07.002

摘要/Abstract

摘要：

目的探讨2例由BCHE基因复合杂合变异导致的丁酰胆碱酯酶缺乏症（BCHED）患儿的临床特征和基因变异分析结果。方法分析2例BCHED患儿临床特征,并行全外显子家系检测,通过生物信息学分析评估变异位点的危害性,并对变异位点进行Sanger测序验证。结果 2例BCHED患儿均出现血清胆碱酯酶异常降低及胆红素升高,但无肝功能损伤。患儿1出现新生儿腹泻症状,患儿2出现新生儿黄疸症状。基因检测结果显示,2例患儿BCHE基因均发生复合杂合变异（患儿1为c.401_c.402insA与c.221delC;患儿2为c.401_c.402insA与c.127G>A）。Sanger测序证实存在变异位点,检索ClinVar及HGMD数据库,未见c.221delC及c.127G>A的相关报道。结论通过2例BCHED患儿不同表型及BCHE基因新变异的发现,进一步拓展了该基因变异谱-表型谱。

关键词: 丁酰胆碱酯酶, BCHE基因, 杂合变异, 丁酰胆碱酯酶缺乏症

Abstract:

Objective To investigate the clinical characteristic and genetic variation analysis of 2 cases of neonatal butyrylcholinesterase deficiency（BCHED） caused by compound heterozygous mutation of BCHE gene. Methods Totally,the clinical characteristics of 2 cases of BCHED were analyzed,and trio-based whole-exome sequencing was performed. The harm of variants was evaluated by bioinformatics analysis,which were verified by Sanger sequencing. Results The 2 cases had decreased serum cholinesterase and increased bilirubin,without liver function injure. Case 1 had neonatal diarrhea symptom,and Case 2 had neonatal jaundice symptom. The results of genetic analysis showed that there were compound heterozygous mutations（c.401_c.402insA and c.221delC; c.401_c.402insA and c.127G>A） in BCHE gene in the 2 cases. Sanger sequencing confirmed the existence of mutation. c.221delC and c.127G>A were not reported in ClinVar and HGMD databases,which were new mutations. Conclusions The gene variation and phenotype spectra have further expanded through the discovery of different phenotypes and new variations of BCHE gene in the 2 neonatal cases of BCHED.

Key words: Butyrylcholinesterase, BCHE gene, Heterozygous mutation, Butyrylcholinesterase deficiency

中图分类号:

Q556

王娟, 余静, 陈珺, 郑洪, 戴立英. BCHE基因复合杂合变异致丁酰胆碱酯酶缺乏症临床特征和遗传分析[J]. 检验医学, 2022, 37(7): 610-614.

WANG Juan, YU Jing, CHEN Jun, ZHENG Hong, DAI Liying. Clinical characteristic and genetic variation analysis of compound heterozygous mutation of BCHE gene leading to neonatal butyrylcholinesterase deficiency[J]. Laboratory Medicine, 2022, 37(7): 610-614.

图/表 3

参考文献 17

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病例	血细胞比容/ %	血红蛋白/（g/L）	白细胞计数/（×10⁹/L）	中性粒细胞百分比/%	淋巴细胞百分比/%	单核细胞百分比/%	嗜酸性粒细胞百分比/%	嗜碱性粒细胞百分比/%
患儿1	40.5	136	11.61	36.0	44.8	14.6	4.1	0.50
患儿2	47.2	110	13.32	42.0	35.6	8.8	5.1	0.40
参考区间	37~50	170~200	15~20	41~70	24~48	1~5	1~5	0~1
病例	血小板计数/（×10⁹/L）	红细胞计数/（×10¹²/L）	网织红细胞百分比/%	钙/ （mmol/L）	磷/ （mmol/L）	钾/ （mmol/L）	总蛋白/ （g/L）	白蛋白/ （g/L）
患儿1	551	4.2	0.008	2.77	1.70	5.69	68.1	46.2
患儿2	620	3.7	0.005	2.49	2.30	5.40	72.0	50.6
参考区间	100~300	5.2~6.4	0.005~0.015	2.2~2.6	0.8~1.6	3.5~5.5	60~82	30~55
病例	球蛋白/ （g/L）	ALT/ （IU/L）	AST/ （IU/L）	TB/ （μmol/L）	DBil/ （μmol/L）	IBil/ （μmol/L）	γ-谷氨酰基转移酶/（IU/L）	胆碱酯酶/ （U/L）
患儿1	21.9	29.0	45.0	74.0	11.2	62.8	78	149
患儿2	31.2	50.0	30.0	97.0	18.8	102.2	110	32
参考区间	25~35	5~60	10~60	2~21	0~8	2~18	0~50	4 000~13 000

病例	血细胞比容/ %	血红蛋白/（g/L）	白细胞计数/（×10⁹/L）	中性粒细胞百分比/%	淋巴细胞百分比/%	单核细胞百分比/%	嗜酸性粒细胞百分比/%	嗜碱性粒细胞百分比/%
患儿1	40.5	136	11.61	36.0	44.8	14.6	4.1	0.50
患儿2	47.2	110	13.32	42.0	35.6	8.8	5.1	0.40
参考区间	37~50	170~200	15~20	41~70	24~48	1~5	1~5	0~1
病例	血小板计数/（×10⁹/L）	红细胞计数/（×10¹²/L）	网织红细胞百分比/%	钙/ （mmol/L）	磷/ （mmol/L）	钾/ （mmol/L）	总蛋白/ （g/L）	白蛋白/ （g/L）
患儿1	551	4.2	0.008	2.77	1.70	5.69	68.1	46.2
患儿2	620	3.7	0.005	2.49	2.30	5.40	72.0	50.6
参考区间	100~300	5.2~6.4	0.005~0.015	2.2~2.6	0.8~1.6	3.5~5.5	60~82	30~55
病例	球蛋白/ （g/L）	ALT/ （IU/L）	AST/ （IU/L）	TB/ （μmol/L）	DBil/ （μmol/L）	IBil/ （μmol/L）	γ-谷氨酰基转移酶/（IU/L）	胆碱酯酶/ （U/L）
患儿1	21.9	29.0	45.0	74.0	11.2	62.8	78	149
患儿2	31.2	50.0	30.0	97.0	18.8	102.2	110	32
参考区间	25~35	5~60	10~60	2~21	0~8	2~18	0~50	4 000~13 000