PDF(Pubmed)
Abstract：
UNASSIGNED: Pathogenic variants in the IGHMBP2 gene are associated with two distinct autosomal recessive neuromuscular disorders: spinal muscular atrophy with respiratory distress type 1 (SMARD1; OMIM #604320) and Charcot-Marie-Tooth type 2S (CMT2S; OMIM #616155). SMARD1 is a severe and fatal condition characterized by infantile-onset respiratory distress, diaphragmatic palsy, and distal muscular weakness, while CMT2S follows a milder clinical course, with slowly progressive distal muscle weakness and sensory loss, without manifestations of respiratory disorder.
UNASSIGNED: Whole-exome sequencing of the IGHMBP2 gene was performed for eight Vietnamese patients with IGHMBP2-related neuromuscular disorders including five patients with SMARD1 and the others with CMT2S.
UNASSIGNED: We identified one novel IGHMBP2 variant c.1574T > C (p.Leu525Pro) in a SMARD1 patient. Besides that, two patients shared the same pathogenic variants (c.1235 + 3A > G/c.1334A > C) but presented completely different clinical courses: one with SMARD1 who deceased at 8 months of age, the other with CMT2S was alive at 3 years old without any respiratory distress.
UNASSIGNED: This study is the first to report IGHMBP-2-related neuromuscular disorders in Vietnam. A novel IGHMBP2 variant c.1574T > C (p.Leu525Pro) expressing SMARD1 phenotype was detected. The presence of three patients with the same genotype but distinct clinical outcomes suggested the interaction of variants and other factors including relating modified genes in the mechanism of various phenotypes.
UNASSIGNED: Whole-exome sequencing of the IGHMBP2 gene was performed for eight Vietnamese patients with IGHMBP2-related neuromuscular disorders including five patients with SMARD1 and the others with CMT2S.
UNASSIGNED: We identified one novel IGHMBP2 variant c.1574T > C (p.Leu525Pro) in a SMARD1 patient. Besides that, two patients shared the same pathogenic variants (c.1235 + 3A > G/c.1334A > C) but presented completely different clinical courses: one with SMARD1 who deceased at 8 months of age, the other with CMT2S was alive at 3 years old without any respiratory distress.
UNASSIGNED: This study is the first to report IGHMBP-2-related neuromuscular disorders in Vietnam. A novel IGHMBP2 variant c.1574T > C (p.Leu525Pro) expressing SMARD1 phenotype was detected. The presence of three patients with the same genotype but distinct clinical outcomes suggested the interaction of variants and other factors including relating modified genes in the mechanism of various phenotypes.
摘要：
■IGHMBP2基因中的致病变体与两种不同的常染色体隐性神经肌肉疾病有关：伴有呼吸窘迫的脊髓性肌萎缩症1型（SMARD1；OMIM＃604320）和Charcot-Marie-Tooth型2S（CMT2S；OMIM＃616155）。SMARD1是一种严重且致命的疾病，其特征是婴儿发作性呼吸窘迫，膈肌麻痹,远端肌肉无力，而CMT2S遵循较温和的临床过程，缓慢进展的远端肌肉无力和感觉丧失，没有呼吸障碍的表现。
■对8名与IGHMBP2相关的神经肌肉疾病的越南患者进行了IGHMBP2基因的全外显子组测序，其中包括5名SMARD1患者和其他CMT2S患者。
■我们鉴定了一个新的IGHMBP2变体c.1574T>C（p。Leu525Pro）在SMARD1患者中。除此之外,两名患者共有相同的致病变异（c.1235+3A>G/c.1334A>C），但表现出完全不同的临床过程：一名患者在8个月大时死亡，另一个患有CMT2S的患者在3岁时还活着，没有任何呼吸窘迫。
■本研究首次报道了越南与IGHMBP-2相关的神经肌肉疾病。一种新的IGHMBP2变体c.1574T>C（p。检测到Leu525Pro)表达SMARD1表型。具有相同基因型但不同临床结果的三名患者的存在表明变体和其他因素的相互作用，包括在各种表型的机制中相关的修饰基因。
■对8名与IGHMBP2相关的神经肌肉疾病的越南患者进行了IGHMBP2基因的全外显子组测序，其中包括5名SMARD1患者和其他CMT2S患者。
■我们鉴定了一个新的IGHMBP2变体c.1574T>C（p。Leu525Pro）在SMARD1患者中。除此之外,两名患者共有相同的致病变异（c.1235+3A>G/c.1334A>C），但表现出完全不同的临床过程：一名患者在8个月大时死亡，另一个患有CMT2S的患者在3岁时还活着，没有任何呼吸窘迫。
■本研究首次报道了越南与IGHMBP-2相关的神经肌肉疾病。一种新的IGHMBP2变体c.1574T>C（p。检测到Leu525Pro)表达SMARD1表型。具有相同基因型但不同临床结果的三名患者的存在表明变体和其他因素的相互作用，包括在各种表型的机制中相关的修饰基因。
