McLeod综合征的XK基因新突变位点一家系研究

A McLeod syndrome family and new novel XK gene mutation

目的 探讨XK基因突变导致的McLeod综合征的临床特征及遗传学特点。 方法 收集1例于2017年5月入住南京医科大学附属脑科医院,表现为McLeod综合征的中年男性患者的临床资料,并对该患者进行全基因组外显子检测,发现XK基因异常,后检测先证者亲属的基因进行验证。 结果 该先证者及其哥哥临床均表现为全身的舞蹈症、外周血棘红细胞、血清肌酸激酶增高。其家系分析符合性X染色体隐性遗传。先证者携带XK基因c.1004G>A突变。疾病数据库尚未报道该突变位点,该位点突变可使XK蛋白丧失最后一个跨膜结构,影响蛋白功能。先证者及其哥哥为半合突变,一位姐姐为正常纯合子,其另一位姐姐、先证者的母亲和女儿为杂合突变,在家庭成员中验证此突变位点,符合家系共分离特点。 结论 报道了中国大陆首例McLeod综合征的家系,并通过血液学和基因检测得到证实,同时发现XK基因的一个新突变位点。建议对中老年男性患者,若出现舞蹈症、心脏病、血清肌酸激酶升高等多系统症状,需常规行XK基因筛查排除McLeod综合征。

Objective To explore the clinical and genetic features of McLeod syndrome caused by XK gene mutation. Methods The clinical data of a patient who came from the Affiliated Brain Hospital of Nanjing Medical University in May 2017 and diagnosed as McLeod syndrome by gene detection were analyzed. Gene analysis was also carried out in his family to confirm the result. Results Acanthocytes in peripheral blood, systemic chorea symptom, and increased serum levels of creatine kinase were observed in this patient and his brother. The proband and his brother showed half mutations. One of the proband′s sister was homozygous normal. The proband′s mother, one of the proband′s sister and the proband′s daughter showed heterozygous mutations. The family analysis accorded with X-linked recessive inheritance trait. Genetic testing for mutations in the XK gene revealed a previously unreported hemizygous single base-pair frame shift deletion at exon 3 (c.1004G>A). Conclusions A rare phenotype of a patient with McLeod syndrome is first described in mainland of China which was discovered coincidentally during routine blood group testing and consecutively genetically confirmed. One novel mutation in XK gene was found in the patient. For old male patient with multiple system disorders including dyskinetic movement disorders, cardiopathy, acanthocytes and elevated serum creatine kinase, a genetic test for XK gene mutation is highly suggested to confirm the McLeod syndrome.