Institute of Human Genetics, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Erlangen, Germany.
Institute of Biochemistry, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Erlangen, Germany.
Sci Rep. 2017 Sep 22;7(1):12225. doi: 10.1038/s41598-017-12465-6.
Short stature is a common pediatric disorder affecting 3% of the population. However, the clinical variability and genetic heterogeneity prevents the identification of the underlying cause in about 80% of the patients. Recently, heterozygous mutations in the ACAN gene coding for the proteoglycan aggrecan, a main component of the cartilage matrix, were associated with idiopathic short stature. To ascertain the prevalence of ACAN mutations and broaden the phenotypic spectrum in patients with idiopathic short stature we performed sequence analyses in 428 families. We identified heterozygous nonsense mutations in four and potentially disease-causing missense variants in two families (1.4%). These patients presented with a mean of -3.2 SDS and some suggestive clinical characteristics. The results suggest heterozygous mutations in ACAN as a common cause of isolated as well as inherited idiopathic short stature.
身材矮小是一种常见的儿科疾病，影响了 3%的人群。然而，临床变异性和遗传异质性使得大约 80%的患者无法确定其根本原因。最近，编码软骨基质主要成分蛋白聚糖聚集素的 ACAN 基因的杂合突变与特发性身材矮小有关。为了确定 ACAN 突变的患病率，并拓宽特发性身材矮小患者的表型谱，我们对 428 个家族进行了序列分析。我们在两个家族（1.4%）中发现了杂合无义突变和两个可能致病的错义变体。这些患者的平均身高标准差（SDS）为-3.2，并有一些提示性的临床特征。研究结果表明，ACAN 的杂合突变是孤立性和遗传性特发性身材矮小的常见原因。
