Department of Pediatric Hematology and Oncology, West China Second University Hospital, Sichuan University, No. 20 Section 3, South Renmin Road, Chengdu, 610041, Sichuan Province, China.
Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Ministry of Education, Chengdu, 610041, Sichuan Province, China.
BMC Pediatr. 2024 Jan 20;24(1):62. doi: 10.1186/s12887-024-04552-1.
Radioulnar synostosis with amegakaryocytic thrombocytopenia (RUSAT) type 2, caused by MDS1 and EVI1 complex locus (MECOM) gene mutations, is a rare inherited bone marrow failure syndrome (IBMFS) with skeletal anomalies, characterized by varying presentation of congenital thrombocytopenia (progressing to pancytopenia), bilateral proximal radioulnar synostosis, and other skeletal abnormalities. Due to limited knowledge and heterogenous manifestations, clinical diagnosis of the disease is challenging. Here we reported a novel MECOM mutation in a Chinese boy with typical clinical features for RUSAT-2. Trio-based whole exome sequencing of buccal swab revealed a novel heterozygous missense mutation in exon 11 of the MECOM gene (chr3:168818673; NM_001105078.3:c.2285G > A). The results strongly suggest that the variant was a germline mutation and disease-causing mutation. The patient received matched unrelated donor hematopoetic stem cell transplantation (HSCT). This finding was not only expanded the pathogenic mutation spectrum of MECOM gene, but also provided key information for clinical diagnosis and treatment of RUSAT-2.
MDS1 和 EVI1 复合基因座(MECOM)基因突变导致的桡尺骨融合伴巨核细胞减少性血小板减少症(RUSAT)2 型是一种罕见的遗传性骨髓衰竭综合征(IBMFS),伴有骨骼异常,其特征为先天性血小板减少症(进展为全血细胞减少症)、双侧近侧桡尺骨融合和其他骨骼异常。由于认识有限且表现多样,该疾病的临床诊断具有挑战性。本研究报道了一例中国男孩的 MECOM 基因突变,该男孩具有典型的 RUSAT-2 临床特征。基于三核苷酸的口腔拭子全外显子组测序显示 MECOM 基因第 11 外显子的一个新型杂合错义突变(chr3:168818673;NM_001105078.3:c.2285G > A)。结果强烈提示该变异为种系突变和致病变异。该患者接受了匹配的无关供体造血干细胞移植(HSCT)。该发现不仅扩大了 MECOM 基因突变的致病突变谱,还为 RUSAT-2 的临床诊断和治疗提供了关键信息。