Abstract: Objective　To improve the understanding of the disease and the accuracy of diagnosis by studying the clinical and genetic characteristics of familial short stature caused by ACAN gene mutation and reviewing relevant literature. Methods　The clinical data and genetic test results of 7 children with familial short stature diagnosed from March 2017 to December 2020 by ACAN gene mutation were retrospectively analyzed. Results　All patients were tested by whole exome sequencing （WES），and the results showed that they all had heterozygous mutations in the ACAN gene.Seven patients were from 4 families，including 5 males and 2 females. All the children went to see the doctor due to slow height growth and had a family history of short stature. There were no osteoarthritis manifestations such as joint pain，restricted joint movement or swelling in the medical history. Among them，2 cases had special facial features，which were characterized by wide eye distance，low nose bridge，collapsed nasal ridge，protruding forehead，and dysplasia in the middle of the face； 3 cases had special physical signs with short neck and wide toes； 2 cases had obvious early bone age. After a full-length spine radiography，it was found that，except for 1 case of sacral cracks，no abnormalities were found in the other patients. Conclusion　Heterozygous mutations in ACAN gene can cause short stature in children and have significant family genetic characteristics. Due to the differences in mutations，some patients may be accompanied by early bone age and special appearance and physical signs.

Key words: familial short stature, genetic characteristics, whole exome sequencing, ACAN gene, heterozygous mutation

摘要： 目的　研究聚集蛋白聚糖（aggrecan，ACAN）基因突变致家族性矮身材的临床特点及遗传学特征，并进行文献复习，以提高对该病的认识及诊断的准确性。方法　回顾性分析2017年3月至2020年12月湖南省人民医院﹑中南大学湘雅二医院及柳州市妇幼保健院诊断的ACAN基因突变致家族性矮身材7例患儿的临床资料及基因检测结果。结果　所有患儿均进行了全外显子测序（WES）检测，结果显示他们都具有ACAN基因的杂合突变。7例患儿分别来自4个家系，其中男性5例，女性2例，患儿均因身高增长缓慢就诊且有身材矮小家族史，病史中均无关节疼痛、关节活动受限及肿大等骨关节炎表现。其中2例有特殊面容，表现为眼距宽、鼻梁低、鼻脊塌陷、前额突出及面中部发育不良；3例有特殊体征，表现为短颈、脚趾宽大；2例有明显的骨龄提前；行脊柱全长片检查除1例有骶椎隐裂外均无异常。结论　ACAN基因杂合变异可导致儿童身材矮小，且具显著的家系遗传特征，由于变异的差异部分患儿可能会伴有骨龄提前的情况及特殊的外貌和体征。

关键词: 家族性矮身材, 遗传学特征, 全外显子测序, ACAN基因, 杂合突变