Abstract：
Mutations in ERLIN2 and MFN2 lead to the development of spastic paraplegia-18 (SPG18) and Charcot-Marie-Tooth type-2A (CMT2A), respectively. These disorders are unified by the fact that both can be termed inherited axonopathies. With whole-exome sequencing (WES), more patients of neurological disorders with clinical overlaps receive a genetic result than ever before. This study describes an Iranian family who harbor mutations in ERLIN2 and MFN2, simultaneously. The proband was a 73-year old man who has experienced weakness and spasticity of lower limbs since late childhood. He was diagnosed with hereditary spastic paraplegia (HSP). His WES identified a novel homozygous variant in ERLIN2 as well as a known heterozygous variant in MFN2. These variants were cosegregated with the phenotypes among the family members. His sister with a similar phenotype just carried the homozygous ERLIN2 variant, whereas, his asymptomatic brother and daughter carried the heterozygous variant of MFN2. Re-evaluation of the MFN2 variant carriers by nerve conduction study revealed that only the proband\'s daughter has peripheral neuropathy. Herein, using WES two distinct disease-causing variants with different modes of inheritance in ERLIN2 and MFN2 were detected in the proband. As expected, individuals with a defined MFN2 variant, p.Arg468His, were asymptomatic or had a mild phenotype. The co-occurrence of such diseases, SPG18 and CMT2A, may result in the milder phenotype to be overlooked or its features considered as a part of the symptoms of other disease. Certainly, providing genetic counseling in such cases can be challenging. These cases reveal the importance of WES.
摘要：
■ERLIN2和MFN2中的突变导致痉挛型截瘫18（SPG18）和Charcot-Marie-Tooth2A（CMT2A）的发展，分别。这些疾病都可以被称为遗传性轴突病。通过全外显子组测序（WES），有临床重叠的神经系统疾病患者比以往任何时候都获得遗传结果。这项研究描述了一个同时在ERLIN2和MFN2中具有突变的伊朗家族。案例介绍：先证者是一名73岁的男子，自童年后期以来就经历了下肢的虚弱和痉挛。他被诊断为遗传性痉挛性截瘫（HSP）。他的WES鉴定了ERLIN2中的新纯合变体以及MFN2中的已知杂合变体。这些变体与家族成员中的表型共分离。他的妹妹具有类似的表型，只是携带了纯合的ERLIN2变体，然而,他无症状的兄弟和女儿携带MFN2的杂合变体。通过神经传导研究对MFN2变体携带者的重新评估显示，只有先证者的女儿患有周围神经病变。
■这里，使用WES在先证者中检测到两种不同的致病变体,它们在ERLIN2和MFN2中具有不同的遗传模式.不出所料,具有确定的MFN2变体的个体，p.Arg468His,无症状或有轻度表型。这些疾病的共同发生，SPG18和CMT2A,可能导致轻度表型被忽视或其特征被认为是其他疾病症状的一部分。当然,在这种情况下提供遗传咨询可能具有挑战性。这些案例揭示了WES的重要性。
■这里，使用WES在先证者中检测到两种不同的致病变体,它们在ERLIN2和MFN2中具有不同的遗传模式.不出所料,具有确定的MFN2变体的个体，p.Arg468His,无症状或有轻度表型。这些疾病的共同发生，SPG18和CMT2A,可能导致轻度表型被忽视或其特征被认为是其他疾病症状的一部分。当然,在这种情况下提供遗传咨询可能具有挑战性。这些案例揭示了WES的重要性。
