Abstract：
OBJECTIVE: This study aimed to report nine Charcot-Marie-Tooth disease (CMT) families with six novel IGHMBP2 mutations in our CMT2 cohort and to summarize the genetic and clinical features of all AR-CMT2S patients reported worldwide.
METHODS: General information, clinical and neurophysiological data of 275 axonal CMT families were collected. Genetic screening was performed by inherited peripheral neuropathy related genes panel or whole exome sequencing. The published papers reporting AR-CMT2S from 2014 to 2023 were searched in Pubmed and Wanfang databases.
RESULTS: In our CMT2 cohort, we detected 17 AR-CMT2S families carrying IGHMBP2 mutations and eight were published previously. Among these, c.743 T > A (p.Val248Glu), c.884A > G (p.Asp295Gly), c.1256C > A (p.Ser419*), c.2598_2599delGA (p.Lys868Sfs*16), c.1694_1696delATG (p.Asp565del) and c.2509A > T (p.Arg837*) were firstly reported. These patients prominently presented with early-onset typical axonal neuropathy and without respiratory dysfunction. So far, 56 AR-CMT2S patients and 57 different mutations coming from 43 families have been reported in the world. Twenty-nine of 32 missense mutations were clustered in helicase domain and ATPase region. The age at onset ranged from 0.11to 20 years (Mean ± SD: 3.43 ± 3.88 years) and the majority was infantile-onset (<2 years). The initial symptoms included weakness of limbs (19, 29.7%), delayed milestones (12, 18.8%), gait disturbance (11, 17.2%), feet deformity (8, 12.5%), feet drop (8, 12.5%), etc. INTERPRETATION: AR-CMT2S accounted for 6.2% in our CMT2 cohort. We firstly reported six novel IGHMBP2 mutations which expanded the genotypic spectrum of AR-CMT2S. Furthermore, 17 AR-CMT2S families could provide more resources for natural history study, drug research and development.
METHODS: General information, clinical and neurophysiological data of 275 axonal CMT families were collected. Genetic screening was performed by inherited peripheral neuropathy related genes panel or whole exome sequencing. The published papers reporting AR-CMT2S from 2014 to 2023 were searched in Pubmed and Wanfang databases.
RESULTS: In our CMT2 cohort, we detected 17 AR-CMT2S families carrying IGHMBP2 mutations and eight were published previously. Among these, c.743 T > A (p.Val248Glu), c.884A > G (p.Asp295Gly), c.1256C > A (p.Ser419*), c.2598_2599delGA (p.Lys868Sfs*16), c.1694_1696delATG (p.Asp565del) and c.2509A > T (p.Arg837*) were firstly reported. These patients prominently presented with early-onset typical axonal neuropathy and without respiratory dysfunction. So far, 56 AR-CMT2S patients and 57 different mutations coming from 43 families have been reported in the world. Twenty-nine of 32 missense mutations were clustered in helicase domain and ATPase region. The age at onset ranged from 0.11to 20 years (Mean ± SD: 3.43 ± 3.88 years) and the majority was infantile-onset (<2 years). The initial symptoms included weakness of limbs (19, 29.7%), delayed milestones (12, 18.8%), gait disturbance (11, 17.2%), feet deformity (8, 12.5%), feet drop (8, 12.5%), etc. INTERPRETATION: AR-CMT2S accounted for 6.2% in our CMT2 cohort. We firstly reported six novel IGHMBP2 mutations which expanded the genotypic spectrum of AR-CMT2S. Furthermore, 17 AR-CMT2S families could provide more resources for natural history study, drug research and development.
摘要：
目的：本研究旨在报告9个Charcot-Marie-Tooth病(CMT)家族，在我们的CMT2队列中具有6个新的IGHMBP2突变，并总结全球报道的所有AR-CMT2S患者的遗传和临床特征。
方法：一般信息，收集了275个轴突CMT家族的临床和神经生理数据.通过遗传性周围神经病变相关基因小组或全外显子组测序进行遗传筛选。在Pubmed和Wanfang数据库中搜索了2014年至2023年报告AR-CMT2S的已发表论文。
结果：在我们的CMT2队列中，我们检测到17个携带IGHMBP2突变的AR-CMT2S家族,其中8个是以前发表的.其中,c.743T>A（p。Val248Glu),c.884A>G（p.Asp295Gly),c.1256C>A（p。Ser419*),c.2598_2599delGA（p。Lys868Sfs*16），c.1694_1696delATG（p。Asp565del）和c.2509A>T（p。首次报道了Arg837*)。这些患者突出表现为早发性典型轴索神经病，无呼吸功能障碍。到目前为止,世界上已经报道了56例AR-CMT2S患者和来自43个家庭的57种不同的突变。32个错义突变中有29个聚集在解旋酶结构域和ATPase区域。发病年龄为0.11至20岁（平均值±SD：3.43±3.88岁），大多数为婴儿发病（<2岁）。最初的症状包括四肢无力（19，29.7%），延迟的里程碑（12，18.8%），步态障碍（11，17.2%），足畸形（8，12.5%），英尺下降(8，12.5%)，等。解释：在我们的CMT2队列中，AR-CMT2S占6.2%。我们首次报道了六个新的IGHMBP2突变，扩展了AR-CMT2S的基因型谱。此外，17个AR-CMT2S家族可以为自然史研究提供更多资源，药物研发。
方法：一般信息，收集了275个轴突CMT家族的临床和神经生理数据.通过遗传性周围神经病变相关基因小组或全外显子组测序进行遗传筛选。在Pubmed和Wanfang数据库中搜索了2014年至2023年报告AR-CMT2S的已发表论文。
结果：在我们的CMT2队列中，我们检测到17个携带IGHMBP2突变的AR-CMT2S家族,其中8个是以前发表的.其中,c.743T>A（p。Val248Glu),c.884A>G（p.Asp295Gly),c.1256C>A（p。Ser419*),c.2598_2599delGA（p。Lys868Sfs*16），c.1694_1696delATG（p。Asp565del）和c.2509A>T（p。首次报道了Arg837*)。这些患者突出表现为早发性典型轴索神经病，无呼吸功能障碍。到目前为止,世界上已经报道了56例AR-CMT2S患者和来自43个家庭的57种不同的突变。32个错义突变中有29个聚集在解旋酶结构域和ATPase区域。发病年龄为0.11至20岁（平均值±SD：3.43±3.88岁），大多数为婴儿发病（<2岁）。最初的症状包括四肢无力（19，29.7%），延迟的里程碑（12，18.8%），步态障碍（11，17.2%），足畸形（8，12.5%），英尺下降(8，12.5%)，等。解释：在我们的CMT2队列中，AR-CMT2S占6.2%。我们首次报道了六个新的IGHMBP2突变，扩展了AR-CMT2S的基因型谱。此外，17个AR-CMT2S家族可以为自然史研究提供更多资源，药物研发。
