PDF(Pubmed)
Abstract：
UNASSIGNED: Charcot-Marie-Tooth disease (CMT) is among the most common group of inherited neuromuscular diseases. SACS mutations were demonstrated to cause autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS). However, there have been few case reports regarding to NEFH and SACS gene mutation to CMT in Vietnamese patients, and the diagnosis of CMT and ARSACS in the clinical setting still overlapped.
UNASSIGNED: We report two patients presenting with sensorimotor neuropathy without cerebellar ataxia, spasticity and other neurological features, being diagnosed with intermediate form CMT by electrophysiological and clinical examination and neuroimaging. By whole-exome sequencing panel of two affected members, and PCR Sanger on NEFH and SACS genes to confirm the presence of selected variants on their parents, we identified a novel missense variant NEFH c.1925C>T (inherited from the mother) in an autosomal dominant heterozygous state, and two recessive SACS variants (SACS c.13174C>T, causing missense variant, and SACS c.11343del, causing frameshift variant) (inherited one from the mother and another from the father) in these two patients. Clinical and electrophysiological findings on these patients did not match classical ARSACS. To the best of our knowledge, this is the first case report of two affected siblings diagnosed with CMT carrying both a novel NEFH variant and biallelic SACS variants.
UNASSIGNED: We concluded that this novel NEFH variant is likely benign, and biallelic SACS mutation (c.13174C>T and c.11343del) is likely pathogenic for intermediate form CMT. This study is also expected to emphasize the current knowledge of intermediate form CMT, ARSACS, and the phenotypic spectrum of NEFH-related and SACS-related disorders. We expect to give a new understanding of CMT; however, further research should be conducted to provide a more thorough knowledge of the pathogenesis of CMT in the future.
UNASSIGNED: We report two patients presenting with sensorimotor neuropathy without cerebellar ataxia, spasticity and other neurological features, being diagnosed with intermediate form CMT by electrophysiological and clinical examination and neuroimaging. By whole-exome sequencing panel of two affected members, and PCR Sanger on NEFH and SACS genes to confirm the presence of selected variants on their parents, we identified a novel missense variant NEFH c.1925C>T (inherited from the mother) in an autosomal dominant heterozygous state, and two recessive SACS variants (SACS c.13174C>T, causing missense variant, and SACS c.11343del, causing frameshift variant) (inherited one from the mother and another from the father) in these two patients. Clinical and electrophysiological findings on these patients did not match classical ARSACS. To the best of our knowledge, this is the first case report of two affected siblings diagnosed with CMT carrying both a novel NEFH variant and biallelic SACS variants.
UNASSIGNED: We concluded that this novel NEFH variant is likely benign, and biallelic SACS mutation (c.13174C>T and c.11343del) is likely pathogenic for intermediate form CMT. This study is also expected to emphasize the current knowledge of intermediate form CMT, ARSACS, and the phenotypic spectrum of NEFH-related and SACS-related disorders. We expect to give a new understanding of CMT; however, further research should be conducted to provide a more thorough knowledge of the pathogenesis of CMT in the future.
摘要：
未经证实：Charcot-Marie-Tooth病（CMT）是最常见的遗传性神经肌肉疾病之一。SACS突变被证明会导致Charlevoix-Saguenay（ARSACS）的常染色体隐性遗传性痉挛性共济失调。然而,在越南患者中，关于CMT的NEFH和SACS基因突变的病例报道很少，CMT和ARSACS在临床上的诊断仍然重叠。
未经证实：我们报告了两名表现为无小脑共济失调的感觉运动神经病的患者，痉挛和其他神经特征，通过电生理和临床检查和神经影像学诊断为中间型CMT。通过两个受影响成员的全外显子组测序小组，并对NEFH和SACS基因进行PCRSanger，以确认其父母上存在选定的变体，我们发现了一个新的错义变异NEFHc.1925C>T（遗传自母亲）在常染色体显性杂合状态，和两个隐性SACS变体（SACSc.13174C>T，导致错觉变异，和SACSc.11343del，在这两名患者中引起移码变异）（从母亲那里继承了一个，从父亲那里继承了另一个）。这些患者的临床和电生理发现与经典的ARSACS不匹配。据我们所知,这是2例受影响的兄弟姐妹被诊断为携带新型NEFH变异体和双等位基因SACS变异体的CMT的首例病例报告.
UNASSIGNED：我们得出结论，这种新型NEFH变体可能是良性的，双等位基因SACS突变（c.13174C>T和c.11343del）可能是中间形式CMT的致病性。这项研究也有望强调中间形式CMT的当前知识，ARSACS,以及NEFH相关和SACS相关疾病的表型谱。我们希望对CMT有新的认识；然而，未来应进行进一步的研究，以提供对CMT发病机制的更透彻的认识。
未经证实：我们报告了两名表现为无小脑共济失调的感觉运动神经病的患者，痉挛和其他神经特征，通过电生理和临床检查和神经影像学诊断为中间型CMT。通过两个受影响成员的全外显子组测序小组，并对NEFH和SACS基因进行PCRSanger，以确认其父母上存在选定的变体，我们发现了一个新的错义变异NEFHc.1925C>T（遗传自母亲）在常染色体显性杂合状态，和两个隐性SACS变体（SACSc.13174C>T，导致错觉变异，和SACSc.11343del，在这两名患者中引起移码变异）（从母亲那里继承了一个，从父亲那里继承了另一个）。这些患者的临床和电生理发现与经典的ARSACS不匹配。据我们所知,这是2例受影响的兄弟姐妹被诊断为携带新型NEFH变异体和双等位基因SACS变异体的CMT的首例病例报告.
UNASSIGNED：我们得出结论，这种新型NEFH变体可能是良性的，双等位基因SACS突变（c.13174C>T和c.11343del）可能是中间形式CMT的致病性。这项研究也有望强调中间形式CMT的当前知识，ARSACS,以及NEFH相关和SACS相关疾病的表型谱。我们希望对CMT有新的认识；然而，未来应进行进一步的研究，以提供对CMT发病机制的更透彻的认识。
