Objective: To summarize the clinical characteristics and gene variants of 2 pedigrees of non-muscle myosin heavy chain 9 related diseases (MYH9-RD) in children. Methods: 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. Results: 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). Conclusions: 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.
目的： 总结儿童非肌性肌球蛋白重链9相关疾病（MYH9-RD）2家系的临床特征及基因变异特点。 方法： 回顾性分析2021年11月及2022年7月郑州大学第一附属医院确诊的2个家系MYH9-RD患者的一般情况、临床表现、基因变异和实验室检查结果，并以“nonmuscle myosin heavy chain 9 related disease”“MYH9”“children”以及“非肌性肌球蛋白重链9相关疾病”“儿童”为关键词分别检索Pubmed数据库、中国知网、万方数据库建库至2023年2月的相关文献，对MYH9-RD基因变异谱及临床资料分析总结。 结果： 先证者1，男，11岁，因鼻衄就诊，先证者长姐、次姐仅表现为月经量过多，先证者母亲磕碰后皮肤黏膜易出现瘀斑，先证者舅舅有肾脏损伤，先证者外祖母及外曾祖母有白内障病史，共7例表型异常。高通量测序显示先证者1 MYH9基因存在c.279C>G（p.N93K）错义突变，家系验证分析显示该变异遗传自患儿母亲。先证者1及家系成员共4例患者诊断为MYH9-RD。先证者2，女，1岁，因发热、咳嗽就诊，患儿父亲为体检发现MYH9-RD。高通量测序显示先证者2 MYH9基因存在c.4270G>A（p.D1424N）错义突变，家系验证分析显示该变异遗传自患儿父亲。先证者2及其父亲共2例患者诊断为MYH9-RD。共检索到文献99篇（国内32篇、国外67篇），MYH9-RD病例共计149个家系、197例散发患者（包括本组2个家系）。临床资料完整的病例共101例（62例散发、39例家系），男56例、女45例，平均年龄6.9岁，主要临床表现为血小板减低、皮肤瘀点瘀斑、鼻衄。大多数患者确诊后未予特殊治疗。检索到MYH9基因 c.279C>G突变致MYH9-RD的英文文献6篇，意大利报道的病例数最多（3例）；MYH9基因 c.4270G>A突变致MYH9-RD的文献11篇，中国报道的病例数最多（9例）。 结论： MYH9-RD家系内发病患者临床表现差异较大，MYH9基因c.279C>G及c.4270G>A突变是MYH9-RD的致病原因。.