Dong Yuehua, Pei Shaohua, Yang Zirao, Xue Yanyan, Wang He
Department of Endocrinology, Baoding, NO. 1 Central Hospital, Baoding, Hebei, China.
Graduate School of Hebei Medical University, Shijiazhuang, Hebei, China.
Ital J Pediatr. 2025 Jun 23;51(1):199. doi: 10.1186/s13052-025-02050-3.
Acromesomelic dysplasia Maroteaux type (AMDM) is a rare autosomal recessive skeletal dysplasia with an estimated prevalence of 1:1,000,000. It is characterized by extreme shortening of the forelimbs and disproportionate short stature.
Here we present the clinical and genetic features of an 8-year-8-month-old boy exhibiting idiopathic short stature and abnormal changes of the appendicular skeleton and axial skeleton, consistent with the established phenotypic spectrum of AMDM. Using diagnostic exome sequencing, we identified two variants in NPR2: a known pathogenic nonsense variant, C.2965 C > T (p.Arg989*), and a missense variant of unknown significance, C.2291T > C (p.Leu764Pro), which has never been reported before. Sanger sequencing confirmed that the variants were inherited from his phenotypically normal parents. The proband is compound heterozygous, while both parents are heterozygous carriers, indicating an autosomal recessive pattern of inheritance.
This study enriches the pathogenic gene mutation spectrum of NPR2 in patients with AMDM and further emphasizes the application of molecular genetic detection in the diagnosis of rare skeletal abnormalities.
马罗泰克斯型肢端中胚层发育不良（AMDM）是一种罕见的常染色体隐性骨骼发育不良，估计患病率为1:1,000,000。其特征是前肢极度缩短和身材比例失调。
在此，我们报告一名8岁8个月大男孩的临床和遗传特征，该男孩表现为特发性身材矮小以及四肢骨骼和中轴骨骼的异常变化，与已确定的AMDM表型谱一致。通过诊断性外显子组测序，我们在NPR2基因中鉴定出两个变异：一个已知的致病性无义变异，即C.2965C>T（p.Arg989*），以及一个意义不明的错义变异，C.2291T>C（p.Leu764Pro），此前从未有过相关报道。桑格测序证实这些变异是从其表型正常的父母遗传而来。先证者为复合杂合子，而父母双方均为杂合子携带者，表明为常染色体隐性遗传模式。
本研究丰富了AMDM患者NPR2基因的致病基因突变谱，并进一步强调了分子遗传学检测在罕见骨骼异常诊断中的应用。
