x连锁肌小管肌病:一种扩大表型异质性肌病基因型谱的新突变。

IF 0.4 Q4 PEDIATRICS
Andreia Carvalho, Carmen Costa, Miguel Pinto, Ricardo Taipa, Ana Gonçalves, Márcia E Oliveira, Sofia Ferreira, Joana Afonso Ribeiro
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引用次数: 0

摘要

x连锁肌小管肌病(XLMTM)是一种继发于编码肌小管蛋白的MTM1基因致病性变异的核中心性先天性肌病,其典型的严重表型包括新生儿张力低下、严重肌肉无力、长期呼吸机依赖、明显延迟的大运动里程碑,无法独立行走,以及新生儿和儿童的高死亡率。然而,温和的先天性形式的条件和其他表型是公认的。我们描述了一个6岁的男孩与轻度XLMTM表型独立的步态,没有呼吸功能不全,甚至在新生儿期。该患儿MTM1基因(c.232-25A > T)具有半合子剪接位点变异,其致病性经cDNA研究(外显子5跳脱)和肌肉活检结果证实。我们还将该患者的表型与少数报道的出生时表现为轻度XLMTM表型且无呼吸窘迫的病例进行了比较,并讨论了这种表型的潜在机制,如正常肌小管蛋白转录物的残留表达。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
X-Linked Myotubular Myopathy: A Novel Mutation Expanding the Genotypic Spectrum of a Phenotypically Heterogeneous Myopathy.

X-linked myotubular myopathy (XLMTM), a centronuclear congenital myopathy secondary to pathogenic variants in the MTM1 gene encoding myotubularin, is typically recognized for its classic and severe phenotype which includes neonatal hypotonia, severe muscle weakness, long-term ventilator dependence, markedly delayed gross motor milestones with inability to independently ambulate, and a high neonatal and childhood mortality. However, milder congenital forms of the condition and other phenotypes are recognized. We describe a 6-year-old boy with a mild XLMTM phenotype with independent gait and no respiratory insufficiency even in the neonatal period. The child has a hemizygous novel splice site variant in the MTM1 gene (c.232-25A > T) whose pathogenicity was confirmed by cDNA studies (exon 5 skipping) and muscle biopsy findings. We also compared the phenotype of our patient with the few reported cases that presented a mild XLMTM phenotype and no respiratory distress at birth, and discussed the potential mechanisms underlying this phenotype such as the presence of residual expression of the normal myotubularin transcript.

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来源期刊
自引率
0.00%
发文量
32
期刊介绍: The Journal of Pediatric Genetics is an English multidisciplinary peer-reviewed international journal publishing articles on all aspects of genetics in childhood and of the genetics of experimental models. These topics include clinical genetics, molecular genetics, biochemical genetics, medical genetics, dysmorphology, teratology, genetic counselling, genetic engineering, formal genetics, neuropsychiatric genetics, behavioral genetics, community genetics, cytogenetics, hereditary or syndromic cancer genetics, genetic mapping, reproductive genetics, fetal pathology and prenatal diagnosis, multiple congenital anomaly syndromes, and molecular embryology of birth defects. Journal of Pediatric Genetics provides an in-depth update on new subjects and current comprehensive coverage of the latest techniques used in the diagnosis of childhood genetics. Journal of Pediatric Genetics encourages submissions from all authors throughout the world. The following articles will be considered for publication: editorials, original and review articles, short report, rapid communications, case reports, letters to the editor, and book reviews. The aim of the journal is to share and disseminate knowledge between all disciplines in the field of pediatric genetics. This journal is a publication of the World Pediatric Society: http://www.worldpediatricsociety.org/ The Journal of Pediatric Genetics is available in print and online. Articles published ahead of print are available via the eFirst service on the Thieme E-Journals platform.
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