3例ACAN基因突变致矮小症病例家系分析及文献复习

doi:10.16150/j.1671-2870.2023.05.005

摘要/Abstract

摘要：

目的：分析3例ACAN基因突异致矮小症患儿的临床特征及遗传改变。方法：收集上海交通大学医学院附属瑞金医院2018年至2020年期间收治的3例ACAN基因突变的矮小患儿的临床资料、实验室检查及基因检测结果，并进行文献复习。结果：3例患儿均有矮小家族史，临床表现均有身材矮小，1例伴有胸腰椎前屈位活动度轻度受限，未见其他系统异常，3例患儿中，年龄最大者5岁1月，骨龄与其实际年龄大致相符或稍提前，2例生长激素（growth hormone， GH）激发峰值小于10 μg/L。基因检测显示3例患儿分别存在ACAN基因变异c.G1877A、c.7360_7361del及c.7038_7039insCGGTGT，其中前两者为新发现的突变，在各大数据库尚无报道。应用重组人生长激素后，3例患儿身高均有改善。回顾国内外文献发现，目前共报道120例患儿及216例亲属，其中已在人类基因数据库（The Human Gene Mutation Database, HGMD）中注册与矮小症相关的ACAN基因变异有80种，其中矮小是最主要临床表现，其次是骨骼发育异常，也可表现为仅矮小。结论：ACAN基因突变主要导致患儿身材矮小及骨骼发育异常，其骨骼临床表型多样，也可仅表现为矮小，对于矮小症特别是有矮小家族史的患儿，无论是否伴有骨骼异常，均需警惕该基因突变。

关键词: ACAN基因, 矮小症, 特发性矮小

Abstract:

Objective: To analyze the clinical features and genetic changes of 3 children in short stature with ACAN gene mutation. Methods: The clinical data, laboratory examinations, and genetic testing results of 3 children with ACAN gene mutations diagnosed with short stature at our pediatric endocrine disease clinic from 2018 to 2020 were collected, and the literature was reviewed for analysis and summary. Results: All the three children had a short family history, and their clinical manifestations were short stature. One patient had a slight limitation of the flexion activity of the thoracolumbar spine, and no other system abnormalities were found. Among them, the oldest of the 3 children was 5 years and 1 month, and the bone age was roughly consistent with or slightly advanced than the actual age, and the peak growth hormone challenge in 2 cases was less than 10 μg/L. The variations in the ACAN gene are c.G1877A and c.7360, respectively_ 7361del and c.7038_ 7039insCGGTGT, case 1 and case 2 are novel mutations that have not been reported in major databases. After the application of recombinant human growth hormone, the height of all three children improved. Reviewing the literature at home and abroad, we found that there were 120 children and 216 relatives reported at present. Among them, there were 80 ACAN gene variants related to short stature registered in HGMD, of which short stature was the most important clinical manifestation, followed by skeletal dysplasia. Conclusions: Mutations of ACAN gene mainly lead to short stature and skeletal dysplasia in children, and their clinical bone phenotypes are diverse, which can also only be manifested as short stature. For children with short stature, especially those with short stature family history, no matter whether they have skeletal abnormalities, they should be alert to this gene mutation.

Key words: ACAN gene, Short stature, Idiopathic short stature

中图分类号:

R596
R446

李彦晓, 陆文丽, 王歆琼, 陈烨, 肖园, 董治亚, 马晓宇. 3例ACAN基因突变致矮小症病例家系分析及文献复习[J]. 诊断学理论与实践, 2023, 22(05): 448-453.

LI Yanxiao, LU Wenli, WANG Xinqiong, CHEN Ye, XIAO Yuan, DONG Zhiya, MA Xiaoyu. Case analysis and literature review of 3 children with short stature with ACAN gene mutation[J]. Journal of Diagnostics Concepts & Practice, 2023, 22(05): 448-453.

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Indice	Patient 1	Patient 2	Patient 3
Gender	Male	Female	Male
Age	5 years and 1 month	4 years and 1 month	5 years
Height（cm）	103.3（-2.0 SD）	94.0（-2.52 SD）	101.2(-2.39 SD)
Weight（kg）	18.0	14.6	17.6
BMI（kg/m²）	16.9	16.5	17.2
Bone age（y)	5.75	4	5.5
IGF-1（ng/mL）	162	90	99
GH peak（μg/L）	8.35	12.1	8.9
Gene mutations	c.G1877A	c.7360_7361del	c.7038_7039insCGGTGT
Protein	p. W626	p. E2454fs	p. Arg2349_Glu2350insCysArg
ACMG	Seaked	Seaked	Unknown
Origin	Father	Mather	Mather

Reference	Mutations	S	He/N	Ha/F	J	OA/OD	V	BA
Reference	Mutations	S	He/N	Ha/F	J	OA/OD	V	delayed	advanced
[10]	74	12/74	34/74	24/74	8/74	20/74	20/74	22/45	23/45
[11]	1	0/1	1	1/1	0/1	0/1	1/1	0/1	1/1
[12]	2	1/2	0/2	0/1	0/1	0/2	0/2	1/2	1/2
[13]	1	0/1	1/1	0/1	0/1	0/1	0/1	1/1	0/1
[14]	2	0/2	2/2	2/2	2/2	2/2	0/2	2/2	0/2
[10]	2	1/2	1/2	1/2	1/2	1/2	1/2	1/2	1/2
[15]	5	4/5	1/5	0/5	0/5	0/5	4/5	4/5	1/5
[16]	13	/	/	/	/	/	/	5/13	7/13
[17]	7	2/7	4/7	5/7	0/7	0/7	3/7	6/7	1/7