A novel missense mutation in the MECOM gene in a Chinese boy with radioulnar synostosis with amegakaryocytic thrombocytopenia

• Published in: BMC pediatrics 2024-01, Vol.24 (1), p.62-62, Article 62
• Main Authors: Huang, Duowen, Jiang, Mingyan, Zhu, Yiping, Li, Dongjun, Lu, Xiaoxi, Gao, Ju
• Format: Article
• Language: English
• Subjects: Amino acids; Analysis; Blood platelets; Blood tests; Bone marrow; Care and treatment; Case reports; China; Diagnosis; Families & family life; Gene amplification; Gene mutations; Genetic aspects; Hematopoetic stem cell transplantation; Hemoglobin; Hemorrhage; Humans; Male; MDS1 and EVI1 complex locus (MECOM) gene mutations; MDS1 and EVI1 Complex Locus Protein - genetics; Medical screening; Mutation; Mutation, Missense; Neutrophils; Patients; Pediatrics; Radioulnar synostosis with amegakaryocytic thrombocytopenia (RUSAT); Radius - abnormalities; Stem cells; Synostosis; Thrombocytopenia; Thrombocytopenia - diagnosis; Thrombocytopenia - genetics; Transcription factors; Transcription Factors - genetics; Ulna - abnormalities; Whole-exome sequencing (WES)
• ISSN: 1471-2431; 1471-2431
• 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.