Central Research Facility Cell Sorting, Hannover Medical School, Hannover, Germany.
Haematology and Oncology Department, Great Ormond Street Hospital for Children, London, United Kingdom.
Blood Adv. 2018 Mar 27;2(6):586-596. doi: 10.1182/bloodadvances.2018016501.
Heterozygous mutations in (MDS1 and EVI1 complex locus) have been reported to be causative of a rare association of congenital amegakaryocytic thrombocytopenia and radioulnar synostosis. Here we report on 12 patients with congenital hypomegakaryocytic thrombocytopenia caused by mutations (including 10 novel mutations). The mutations affected different functional domains of the EVI1 protein. The spectrum of phenotypes was much broader than initially reported for the first 3 patients; we found familial as well as sporadic cases, and the clinical spectrum ranged from isolated radioulnar synostosis with no or mild hematological involvement to severe bone marrow failure without obvious skeletal abnormality. The clinical picture included radioulnar synostosis, bone marrow failure, clinodactyly, cardiac and renal malformations, B-cell deficiency, and presenile hearing loss. No single clinical manifestation was detected in all patients affected by mutations. Radioulnar synostosis and B-cell deficiency were observed only in patients with mutations affecting a short region in the C-terminal zinc finger domain of EVI1. We propose the term MECOM-associated syndrome for this heterogeneous hereditary disease and inclusion of sequencing in the diagnostic workup of congenital bone marrow failure.
（MDS1 和 EVI1 复合物基因座）杂合性突变已被报道为先天性巨核细胞减少性血小板减少症和桡尺骨融合的罕见关联的致病原因。在此，我们报告了 12 例由 基因突变引起的先天性低巨核细胞性血小板减少症（包括 10 个新突变）。这些突变影响了 EVI1 蛋白的不同功能域。表型谱比最初报道的前 3 例患者广泛得多；我们发现了家族性和散发性病例，临床谱范围从无明显骨骼异常的孤立性桡尺骨融合、无或轻度血液学受累到严重的骨髓衰竭。临床表现包括桡尺骨融合、骨髓衰竭、指弯曲、心脏和肾脏畸形、B 细胞缺陷和早发性听力损失。受 基因突变影响的所有患者均未检测到单一临床表现。只有当 EVI1 的 C 末端锌指结构域中的短区域受到突变影响时，才会观察到桡尺骨融合和 B 细胞缺陷。我们提出 MECOM 相关综合征这一术语来描述这种异质性遗传性疾病，并建议将 测序纳入先天性骨髓衰竭的诊断评估中。
