Department of Neurology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University, College of Medicine, Kaohsiung, Taiwan; Department of Information Management, National Sun Yat-sen University, Kaohsiung, Taiwan.
Department of Neurology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University, College of Medicine, Kaohsiung, Taiwan.
Mult Scler Relat Disord. 2019 May;30:57-62. doi: 10.1016/j.msard.2019.02.002. Epub 2019 Feb 4.
The aim of the current study was to examine intra-family phenotype variations in familial neuromyelitis optica (NMO) spectrum disorder.
The clinical presentation and neuroimaging features of two family members (mother and daughter) from a NMO spectrum disorder family (index family) were analyzed. Multiplex polymerase chain reaction was performed based on targeted re-sequencing on the AQP4 gene and the human leukocyte antigen (HLA) loci. The clinical and neuroimaging features of the members of six other previously reported NMO spectrum disorder families were also included for analysis.
In the core family, the mother was aged 39 at disease onset and the initial presentation was spinal cord involvement, whereas the daughter was 22 years old at disease onset and the initial presentation was brainstem involvement. No coding pathogenic variants or single nucleotide polymorphisms of the AQP4 gene were identified in the mother, daughter or father. As for HLA genotyping, the HLA-DRB103 and HLA-DPB104 alleles were shared by the mother and daughter. The HLA-DPB1*05 was present in the affected daughter and was inherited from the unaffected father. As for the other six reported families with familial NMO spectrum disorder, four mother-daughter pairs had a different age at disease onset and/or a different initial presentation. The other two affected family groups were sister-sister pairs; they had a similar age of onset and similar initial presentations.
The present study offers a preliminary view of the clinical and neuroimaging features of patients with familial NMO spectrum disorder. Clinical heterogeneities were found among the family members, especially the mother and daughter pairs. The presence of risk allele HLA-DR*03:01 may be an important genetic finding for familial NMO spectrum disorder patients. To the best of our knowledge, this clinical heterogeneity has not been previously examined or reported in the literature. For better delineation of the intra-familial phenotype variations in familial NMO spectrum disorder, further large-scale studies are needed.
本研究旨在探讨家族性视神经脊髓炎谱系疾病（NMOSD）中家族内表型变异。
分析一个 NMOSD 家系（先证家族）中 2 位家庭成员（母亲和女儿）的临床表现和神经影像学特征。基于靶向重测序，对 AQP4 基因和人类白细胞抗原（HLA）位点进行多重聚合酶链反应。同时分析了另外 6 个先前报道的 NMOSD 家系的成员的临床和神经影像学特征。
在核心家系中，母亲发病时 39 岁，首发症状为脊髓受累，而女儿发病时 22 岁，首发症状为脑干受累。在母亲、女儿和父亲中均未发现 AQP4 基因的编码致病性变异或单核苷酸多态性。HLA 基因分型显示，母亲和女儿共享 HLA-DRB103 和 HLA-DPB104 等位基因，受累女儿携带的 HLA-DPB1*05 则来自未受影响的父亲。在另外 6 个报道的家族性 NMOSD 家系中，4 对母女发病年龄和/或首发症状不同。另外 2 个受累家系为姐妹关系，发病年龄和首发症状相似。
本研究初步探讨了家族性 NMOSD 患者的临床和神经影像学特征。家系成员存在临床表现异质性，尤其是母女。HLA-DR*03:01 风险等位基因的存在可能是家族性 NMOSD 患者的一个重要遗传发现。据我们所知，这种临床异质性在文献中尚未被研究或报道过。为了更好地阐明家族性 NMOSD 中的家族内表型变异，需要进一步开展大规模研究。
