一个May-Hegglin异常家系非肌性肌球蛋白重链9基因突变位点的鉴定

目的：鉴定一个May-Hegglin异常（MHA）家系非肌性肌球蛋白重链9基因（MYH9）突变的类型及临床表型特点。方法：用聚合酶链反应（PCR）技术扩增先证者及其父亲的非性肌球蛋白重链9基因（MYH9）的25、31－32、38、40号外显子，分析PCR产物的核苷酸序列。确定突变位点后，分别扩增正常对照、后天获得性血小板减少症患者的对应基因区域并行核苷酸序列分析以资对照。进而进行PCR扩增片段的CpoI(RsrII）限制性内切酶图谱分析。结果：本家系中May-Hegglin异常患者具有典型的“血小板减少、巨大血小板、粒细胞包涵体”三连征。先证者及其父亲在MYH9的38号外显子上第5521位核苷酸存在G→A突变（GAG→AAG),并导致特征性的CpoI限制性内切酶图谱改变。结论：中国人的May-Hegglin异常存在MYH9基因突变。本家系中，其突变位点位于38号外显子（G5521A），MYH9基因突变的传递规律与家系中临床表型分布相符。

Identification of nonmuscle mysin heavy chain 9 gene mutation in a May-Hegglin anomaly family

OBJECTIVE: To describe the clinical phenotype and identify the nonmuscle myosin heavy chain 9 (MYH9) gene mutation in the first May-Hegglin anomaly family in China. METHODS: The exons 25, 31 approximately 32 38 and 40 in the MYH9 gene of the proband and her affected father were amplified with polymerase chain reaction, and the PCR products were sequenced. After the specific point mutation in exon 38 was identified in these two cases, the corresponding region of the MYH9 gene was amplified and nuclear acid sequence analysis was conducted among 30 healthy persons, one patient with idiopathic thrombocytopenic purpura and one patient with thrombotic thrombocytopenic purpura. The CpoI restriction endonuclease map from the PCR products of exon 38 of MYH9 gene was analysed among the proband, her father and other family members, 30 normal controls, 1 ITP patient, and one TTP patient. RESULTS: The proband and her affected father manifested a typical triad of thrombocytopenia, giant platelets, and inclusion bodies in leukocytes. The patient showed mild hemorrhagic tendency since infancy, while the platelet aggregation function was normal. A 5521G --> A mutation (GAG --> AAG) in the exon 38 of the MYH9 gene existed in the proband and her affected father, resulting in a characteristic change in CpoI restriction endonuclease map. CONCLUSION: The cases of May-Heggelin anomaly in China show typical triad of thrombocytopenia, giant platelets, and inclusion bodies in leukocytes too. Mutation of MYH9 gene exists in cases of May-Hegglin anomaly in China. The point mutation is located in exon 38 (G5521A) in this family.