Key Laboratory of Endocrinology of National Health Commission, Department of Endocrinology, Peking Union Medixcal College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, China.
Key Laboratory of Endocrinology of National Health Commission, Department of Endocrinology, Peking Union Medixcal College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, China..
Endocr Pract. 2020 Nov;26(11):1255-1268. doi: 10.4158/EP-2019-0518.
There are numerous reasons for short stature, including mutations in osteochondral development genes. ACAN, one such osteochondral development gene in which heterozygous mutations can cause short stature, has attracted attention from researchers in recent years. Therefore, we analyzed six cases of short stature with heterozygous ACAN mutations and performed a literature review.
Clinical information and blood samples from 6 probands and their family members were collected after consent forms were signed. Gene mutations in the probands were detected by whole-exome sequencing. Then, we searched the literature, performed statistical analyses, and summarized the characteristics of all reported cases.
We identified six novel mutations in ACAN: c.1411C>T, c.1817C>A, c.1762C>T, c.2266G>C, c.7469G>A, and c.1733-1G>A. In the literature, more than 200 affected individuals have been diagnosed genetically with a similar condition (height standard deviation score [SDS] -3.14 ± 1.15). Among affected individuals receiving growth-promoting treatment, their height before and after treatment was SDS -2.92±1.07 versus SDS -2.14±1.23 (P<.001). As of July 1, 2019, a total of 57 heterozygous ACAN mutations causing nonsyndromic short stature had been reported, including the six novel mutations found in our study. Approximately half of these mutations can lead to protein truncation.
This study used clinical and genetic means to examine the relationship between the ACAN gene and short stature. To some extent, clear diagnosis is difficult, since most of these affected individuals' characteristics are not prominent. Growth-promoting therapies may be beneficial for increasing the height of affected patients.
AI = aromatase inhibitor; ECM = extracellular matrix; GnRHa = gonadotropin-releasing hormone analogue; IQR = interquartile range; MIM = Mendelian Inheritance in Man; PGHD = partial growth hormone deficiency; rhGH = recombinant human growth hormone; SDS = standard deviation score; SGA = small for gestational age; SGHD = severe growth hormone deficiency.
身材矮小的原因有很多，包括骨软骨发育基因的突变。ACAN 就是这样一个骨软骨发育基因，其杂合突变可导致身材矮小，近年来引起了研究人员的关注。因此，我们分析了 6 例携带 ACAN 杂合突变的身材矮小患者，并进行了文献回顾。
在签署同意书后，收集了 6 名先证者及其家庭成员的临床信息和血样。通过全外显子组测序检测先证者的基因突变。然后，我们检索文献，进行统计学分析，并总结所有报道病例的特征。
我们在 ACAN 中发现了 6 个新的突变：c.1411C>T、c.1817C>A、c.1762C>T、c.2266G>C、c.7469G>A 和 c.1733-1G>A。在文献中，已有 200 多名受影响的个体通过基因诊断遗传得到了类似的情况（身高标准差评分[SDS] -3.14 ± 1.15）。在接受生长促进治疗的受影响个体中，治疗前后的身高为 SDS -2.92±1.07 与 SDS -2.14±1.23（P<.001）。截至 2019 年 7 月 1 日，共报道了 57 种导致非综合征性身材矮小的杂合 ACAN 突变，包括我们研究中发现的 6 种新突变。这些突变中约有一半可导致蛋白质截断。
本研究采用临床和遗传学方法研究了 ACAN 基因与身材矮小的关系。在某种程度上，由于大多数受影响个体的特征不明显，明确诊断是困难的。生长促进疗法可能有益于增加受影响患者的身高。
AI = 芳香化酶抑制剂；ECM = 细胞外基质；GnRHa = 促性腺激素释放激素类似物；IQR = 四分位距；MIM = 人类孟德尔遗传；PGHD = 部分生长激素缺乏症；rhGH = 重组人生长激素；SDS = 标准差评分；SGA = 小于胎龄儿；SGHD = 严重生长激素缺乏症。
