携带相同DOK7突变的2例无关病例的表型差异。
Phenotypic Differences in 2 Unrelated Cases Carrying Identical DOK7 Mutations.
作者信息
Bissay Véronique, Maselli Ricardo A
机构信息
Department of Neurology, Center for Neurosciences, UZ Brussel, Vrije Universiteit Brussel (VUB), Brussels, Belgium.
Department of Neurology, University of California at Davis, Davis, CA.
出版信息
J Clin Neuromuscul Dis. 2019 Sep;21(1):30-34. doi: 10.1097/CND.0000000000000246.
INTRODUCTION
Mutations in the Dok-7 gene (DOK7) underlie a congenital myasthenic syndrome (CMS) with a characteristic limb-girdle (LG) pattern of muscle weakness. Multiple clinical findings and a wide clinical heterogeneity have been identified in this form of CMS.
METHODS
We describe here 2 unrelated adult patients who presented with a LG CMS, caused by 2 compound heterozygous pathogenic sequence variants in DOK7: c.1124_1127dupTGCC (P.Ala378Serfs30) and c.480C> A (p.Tyr160).
RESULTS
Although both patients presented with severe proximal weakness consistent with LG myasthenia, one of the patients presented with additional distal muscle involvement in the lower extremities. By contrast, the other patient had severe bulbar and respiratory deficit requiring gastric tube feeding and mechanical ventilatory support for most parts of the day.
DISCUSSION
These 2 cases illustrate the lack of phenotype-genotype correlation and the absence of geographic, genetic, and ethnic association in cases of LG CMS caused by DOK7 mutations.
引言
Dok-7基因（DOK7）突变是一种先天性肌无力综合征（CMS）的病因，其特征为具有典型的肢带型（LG）肌无力模式。这种类型的CMS已发现多种临床症状及广泛的临床异质性。
方法
我们在此描述2例无血缘关系的成年患者，他们患有肢带型CMS，由DOK7基因中的2个复合杂合致病性序列变异引起：c.1124_1127dupTGCC（P.Ala378Serfs30）和c.480C>A（p.Tyr160）。
结果
尽管两名患者均表现出与肢带型肌无力相符的严重近端肌无力，但其中一名患者下肢还出现了额外的远端肌肉受累。相比之下，另一名患者有严重的延髓和呼吸功能障碍，一天中的大部分时间都需要鼻饲和机械通气支持。
讨论
这2例病例说明了由DOK7突变引起的肢带型CMS病例中表型与基因型缺乏相关性，以及不存在地域、遗传和种族关联。
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