17q12微缺失综合征3例报告并文献复习

doi:10.12372/jcp.2023.22e0461

摘要/Abstract

摘要： 目的总结儿童染色体17q12微缺失综合征的临床特征，以提高对该病的认识。方法回顾性分析2014年10月至2021年10月收治的3例染色体17q12微缺失综合征患儿临床资料，应用二代测序技术对全基因组染色体拷贝数变异进行检测，并进行相关文献复习。结果 3例患儿中男2例，女1例。染色体17q12均发现大片缺失（分别为1.89Mb，1.4Mb，1.8Mb），缺失均为新发变异；3例均有肾脏囊肿、高尿酸血症和高碱性磷酸酶；2例有单侧肾脏发育不良及蛋白尿；低镁血症2例，高胆固醇血症2例，肝酶升高1例，糖尿病2例。结论染色体17q12微缺失综合征是一种影响多器官系统的罕见遗传性疾病，主要表现为肾脏囊肿和发育不良，也可出现糖尿病、高尿酸血症和高胆固醇血症等代谢内分泌异常。

关键词: 17q12微缺失综合征, 肝细胞核因子1B, 肾囊肿, 遗传性疾病, 儿童

Abstract: Objective To summarize the clinical characteristics of chromosomal 17q12 microdeletion syndrome in children in order to improve the understanding of the disease. Methods The clinical data of 3 children with chromosomal 17q12 microdeletion syndrome admitted from October 2014 to October 2021 were retrospectively analyzed. Genome-wide chromosomal copy number variation was detected by second-generation sequencing and the relevant literature was reviewed. Results Large deletions (1.89Mb, 1.4Mb and 1.8Mb, respectively) were found on chromosome 17q12 of 3 children (2 boys and 1 girl), and the deletions were all de novo variations. All three patients had renal cysts, hyperuricemia and elevated alkaline phosphatase. Two patients had unilateral renal dysplasia and proteinuria. Two patients had hypomagnesemia, 2 had hypercholesterolemia, 2 had diabetes mellitus, and 1 had elevated liver enzymes. Conclusions Chromosome 17q12 microdeletion syndrome is a rare genetic disorder affecting multiple organ systems, mainly manifesting as renal cysts and dysplasia, as well as metabolic and endocrine abnormalities such as diabetes, hyperuricemia, and hypercholesterolemia.

Key words: 17q12 microdeletion syndrome, hepatocyte nuclear factor 1 beta, renal cyst, genetic disease, child

徐永丽, 杨静, 周兰琪, 周建华. 17q12微缺失综合征3例报告并文献复习[J]. 临床儿科杂志, 2023, 41(1): 60-65.

XU Yongli, YANG Jing, ZHOU Lanqi, ZHOU Jianhua. 17q12 microdeletion syndrome: a report of three cases and literature review[J]. Journal of Clinical Pediatrics, 2023, 41(1): 60-65.

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参考文献 34

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项目	例1	例2	例3
诊断年龄/岁	7	8	7
发病年龄/岁	4	8	7
性别	男	男	女
肾病家族史	无	无	无
蛋白尿	无	++	+
微量白蛋白/mg·L^-1	2.6	710.5	189
24小时尿微量总蛋白/mg	59.8	680	415.8
血肌酐/μmo1·L^-1	40	41	271
尿酸/μmo1·L^-1	646.0	583.0	493.0
丙氨酸转氨酶/U·L^-1	21	164	17
天冬氨酸转氨酶/U·L^-1	25	205	29
碱性磷酸酶/U·L^-1	301	327	467
总胆固醇/mmol·L^-1	3.30	8.15	6.5
血镁/mmol·L^-1	0.56	0.46	1.03
糖尿病	+	+	-
肾脏大小/cm	9.9×4.4（左）	6.8×2.4（左）	8.1×2.6（左）
	10.6×4.1（右）	9.5×4.2（右）	5.7×1.5（右）

基因	例1	例2	例3	显性遗传对应疾病
CCL3、CCL4	-	+	-
CCL4L2、CCL3L1、CCL3L3	-	+	-
TBC1D3B/3C/3G/3H/3F	-	+	-
ZNHIT3	-	-	-
MYO19¹⁾	-	-	-	高钾性周期性麻痹
PIGW	-	-	-
GGNBP2	-	-	-
DHRS11	-	-	-
MRM1	-	-	-
LHX1¹⁾	-	-	-	Mayer-Rokitansky-Kuster-Hauser 综合征、输尿管膨出、肾囊肿和糖尿病综合征
AATF	-	-	-
ACACA	-	-	-
C17orf78	-	-	-
TADA2A	-	-	-
DUSP14	-	-	-
SYNRG	-	-	-
DDX52¹⁾	-	-	-	Robinow 综合征、常染色体显性非综合征性智力障碍
HNF1B¹⁾	-	-	-	肾囊肿和糖尿病综合征 ( RCAD )、Hnf1b 相关的ADTKD 、 MODY5 等
YWHAEP7	-	-	-
TBC1D3¹⁾	-	+	-	前列腺癌

项目	占比（%）
年龄	0~18岁（中位数8岁8个月）
性别
男	60.4（29/48）
女	39.6（19/48）
变异类型
新发变异	72.9（35/48）
遗传自父母	27.1（13/48）
肾脏异常
囊性肾病	69.4（34/49）
肾功能不全	26.9（7/26）
低镁血症	54.5（6/11）
高尿酸血症	30.0（3/10）
肝脏异常	39.3（11/28）
胰腺结构性异常	29.4（5/17）
糖尿病	21.3（10/47）
神经精神异常^1）	49.0（25/51）
发育迟缓^2）	59.6（31/52）
面部畸形	51.4（18/35）

肾脏		多囊肾发育不良、慢性肾衰竭、蛋白尿、低镁血症、高尿酸血症皮质-髓质分化不良、肾积水或输尿管扩张、产前超声双侧高回声肾、马蹄形和重复肾、集合系统异常和双侧肾积水、
肝脏		肝功能异常、肝酶水平无症状升高(常见)、碱性磷酸酶(AP)升高、新生儿胆汁淤积症(罕见)、胆管稀少
糖尿病		青年5型成熟型糖尿病(MODY5)
神经系统		神经发育或神经精神障碍(例如发育迟缓、自闭症谱系障碍、注意力缺陷/多动障碍、精神分裂症和双相情感障碍)
其他	胰腺结构性损伤	胰腺发育不全、胰体尾部发育不良伴头部轻度萎缩，可伴胰腺外分泌功能障碍
	生殖系统	MRKH综合征、双角子宫、双胎子宫、残缺子宫、双阴道、双侧或单侧隐睾
	面部畸形	眼睛畸形、斜视、高拱形眉毛、鼻梁塌陷