A Case of McLeod Syndrome with A Novel XK Missense Mutation
A Case of McLeod Syndrome with A Novel XK Missense Mutation
复制标题
伴有新型 XK 错义突变的麦克劳德综合征一例
DOI：
10.1002/mdc3.12614
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发表时间：
2018
期刊：
影响因子：
--
通讯作者：
Tanaka F
中科院分区：
文献类型：
--
作者：
Komiya H;Takasu M;Hashiguchi S;Uematsu E;Fukai R;Tanaka K;Tada M;Joki H;Takahashi T;Koyano S;Doi H;Takeuchi H;Tanaka F
McLeod综合征患者通常出现神经系统表现，包括轴突神经病变、肌病伴高CK血症、心肌病、亨廷顿病样舞蹈病、癫痫发作、行为改变和痴呆。由于McLeod综合征的初始症状多种多样，早期诊断通常很困难。6以前的一项研究报告说，70%的患者发展为舞蹈病。由于舞蹈病是McLeod综合征的一个关键神经学特征，其缺失或迟发可能导致诊断延迟。这是一例罕见的XK基因错义突变病例，在发病27年后出现无特征的远端肌无力后出现非常轻微的舞蹈病。XK基因由三个外显子组成，编码一种具有10个跨膜结构域的膜转运蛋白XK。受损的XK基因功能导致RBC表面上Kx抗原的缺失。目前已知超过30种XK突变导致McLeod血液学表型和综合征。1，2，3，4，7然而，仅报道了三种错义突变：p.Arg222Gly、p.Cys294Arg和p.Glu327Lys。2，3，4我们的患者在第六个跨膜区发现了新的错义p.Arg222Pro突变。错义突变的临床表型通常被预测为比无义或移码突变的临床表型更温和，并且实际上，编码氨基酸Arg 222和Glu 327的基因的错义突变被报道引起McLeod血液学表型，但不是McLeod综合征，因为p.Arg222Gly和p.Glu327Lys突变不损害神经肌肉或脑功能。3，4，8本报告中的新发现是错义突变p.Arg222Pro不仅导致McLeod血液学表型，而且导致McLeod综合征。之前只有一份关于错义突变p.Cys294Arg的报告，该突变导致麦克劳德综合征伴严重神经缺陷，包括肌无力、舞蹈病、癫痫发作、认知障碍和不自主发声，始于44岁。9即使基因型相同且在同一家族中，麦克劳德综合征的临床特征也是可变的，10因此基因型-表型相关性与这种疾病并不非常相关。这些结果可以解释p.Arg222Gly和p.Arg222Pro引起的差异表型。我们的案例可能进一步了解Arg 222残基在XK功能中的重要性。
DiscussionPatients with McLeod syndrome usually develop neurological manifestations, including axonal neuropathy, myopathy with hyperCKemia, cardiomyopathy, Huntington's disease‐like chorea, seizure, behavioral change, and dementia. 2, 5 Since the initial symptoms of McLeod syndrome are diverse, early diagnosis is often difficult. 6 A previous study reported that 70% of patients developed chorea. 2 Because chorea is a key neurological feature of McLeod syndrome, its absence or late onset may lead to a diagnostic delay. This is a rare case with a novel missense mutation of XK in which very mild chorea appeared following featureless distal muscle weakness 27 years after disease onset. The XK gene consists of three exons and encodes XK, a membrane transport protein with 10 transmembrane domains. Impaired XK gene function results in the absence of the Kx antigen on the surface of RBCs. More than 30 XK mutations are currently known to cause McLeod hematologic phenotype and syndrome. 1, 2, 3, 4, 7 However, only three missense mutations have been reported: p. Arg222Gly, p. Cys294Arg, and p. Glu327Lys. 2, 3, 4 Our patient had the novel missense p. Arg222Pro mutation located in the sixth transmembrane domain. The clinical phenotypes of missense mutations are generally predicted to be milder than those of nonsense or frameshift mutations, and indeed, missense mutations of the genes encoding amino acids Arg222 and Glu327 were reported to cause McLeod hematologic phenotype but not McLeod syndrome, because the p. Arg222Gly and p. Glu327Lys mutations do not impair neuromuscular or cerebral functioning. 3, 4, 8 The novel finding in this report is that a missense mutation, p. Arg222Pro, led not only to the McLeod hematologic phenotype, but also to McLeod syndrome. There is only one previous report of a missense mutation, p. Cys294Arg, resulting in McLeod syndrome with severe neurological defects, including muscle weakness, chorea, seizure, cognitive impairment, and involuntary vocalizations, beginning at age 44. 9 The clinical features of McLeod syndrome is variable even with the same genotype and within the same family, 10 therefore the genotype‐phenotype correlation is not very relevant in this disease. These findings may explain the differential phenotypes resulting from p. Arg222Gly and p. Arg222Pro. Our case might further the understanding of the importance of the Arg222 residue in the function of XK.
麦克劳德综合征舞蹈病
影响因子：
8.6
作者：
A. Danek;F. Tison;J. Rubio;M. Oechsner;W. Kalckreuth;A. Monaco
通讯作者：
A. Monaco