Mao S T, Li B, Wang D, Liu S S, Su S F, Wei L L, Chai F Y, Liu Y, Liu Y F
Department of Hematology and Oncology, Children's Hospital, the First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China.
Zhonghua Er Ke Za Zhi. 2023 Sep 2;61(9):833-838. doi: 10.3760/cma.j.cn112140-20230329-00220.
To summarize the clinical characteristics and gene variants of 2 pedigrees of non-muscle myosin heavy chain 9 related diseases (MYH9-RD) in children. The basic information, clinical features, gene variants and laboratory tests of MYH9-RD patients from 2 pedigrees confirmed in the First Affiliated Hospital of Zhengzhou University in November 2021 and July 2022 were analyzed retrospectively. "Non-muscle myosin heavy chain 9 related disease" "MYH9" and "children" were used as key words to search at Pubmed database, CNKI and Wanfang database up to February 2023. The MYH9-RD gene variant spectrum and clinical data were analyzed and summarized. Proband 1 (male, 11 years old) sought medical attention due to epistaxis, the eldest sister and second sister of proband 1 only showed excessive menstrual bleeding, the skin and mucous membrane of the their mother were prone to ecchymosis after bumping, the uncle of proband 1 had kidney damage, and the maternal grandmother and maternal great-grandmother of proband 1 had a history of cataracts. There were 7 cases of phenotypic abnormalities in this pedigree. High-throughput sequencing showed that the proband 1 MYH9 gene had c.279C>G (p.N93K) missense variant, and family verification analysis showed that the variant was inherited from the mother. A total of 4 patients including proband 1 and family members were diagnosed with MYH9-RD. The proband 2 (female, 1 year old) sought medical attention duo to fever and cough, and the father's physical examination revealed thrombocytopenia. There were 2 cases of phenotypic abnormalities in this pedigree. High-throughput sequencing showed that there was a c.4270G>A (p.D1424N) missense variant in the proband 2 MYH9 gene, and family verification analysis showed that the variant was inherited from the father. A total of 2 patients including proband 2 and his father were diagnosed with MYH9-RD. A total of 99 articles were retrieved, including 32 domestic literatures and 67 foreign literatures. The MYH9-RD cases totaled 149 pedigrees and 197 sporadic patients, including 2 pedigrees in our study. There were 101 cases with complete clinical data, including 62 sporadic cases and 39 pedigrees. There were 56 males and 45 females, with an average age of 6.9 years old. The main clinical manifestations were thrombocytopenia, skin ecchymosis, and epistaxis. Most patients didn't receive special treatment after diagnosis. Six English literatures related to MYH9-RD caused by c.279C>G mutation in MYH9 gene were retrieved. Italy reported the highest number of cases (3 cases). Twelve literatures related to MYH9-RD caused by c.4270G>A mutation in MYH9 gene were retrieved. China reported the highest number of cases (9 cases). The clinical manifestations of patients in the MYH9-RD pedigrees varied greatly. MYH9 gene c.279C>G and c.4270G>A mutations are the cause of MYH9-RD.
总结2个儿童非肌球蛋白重链9相关疾病（MYH9-RD）家系的临床特征及基因变异情况。回顾性分析2021年11月及2022年7月在郑州大学第一附属医院确诊的2个MYH9-RD家系患者的基本信息、临床特征、基因变异及实验室检查结果。以“非肌球蛋白重链9相关疾病”“MYH9”“儿童”为关键词，检索截至2023年2月的Pubmed数据库、中国知网和万方数据库。对MYH9-RD基因变异谱及临床资料进行分析总结。先证者1（男，11岁）因鼻出血就诊，先证者1的大姐和二姐仅表现为月经过多，其母亲的皮肤和黏膜在碰撞后易出现瘀斑，先证者1的舅舅有肾脏损害，先证者1的外祖母和曾外祖母有白内障病史。该家系共有7例表型异常。高通量测序显示先证者1的MYH9基因有c.279C>G（p.N93K）错义变异，家系验证分析表明该变异遗传自母亲。包括先证者1及其家庭成员在内，共有4例患者被诊断为MYH9-RD。先证者2（女，1岁）因发热、咳嗽就诊，父亲体检发现血小板减少。该家系有2例表型异常。高通量测序显示先证者2的MYH9基因有c.4270G>A（p.D1424N）错义变异，家系验证分析表明该变异遗传自父亲。包括先证者2及其父亲在内，共有2例患者被诊断为MYH9-RD。共检索到99篇文献，其中国内文献32篇，国外文献67篇。MYH9-RD病例共149个家系及197例散发病例，包括本研究中的2个家系。有101例患者有完整临床资料，其中散发病例62例，家系39个。男性56例，女性45例，平均年龄6.9岁。主要临床表现为血小板减少、皮肤瘀斑及鼻出血。多数患者确诊后未接受特殊治疗。检索到6篇与MYH9基因c.279C>G突变所致MYH9-RD相关的英文文献。意大利报道的病例数最多（3例）。检索到12篇与MYH9基因c.4270G>A突变所致MYH9-RD相关的文献。中国报道的病例数最多（9例）。MYH9-RD家系患者的临床表现差异很大。MYH9基因c.279C>G和c.4270G>A突变是MYH9-RD的病因。
