Background

Pathogenic variants in the IGHMBP2 gene cause recessive spinal motor neuropathies of variable phenotype, including a predominantly distal motor impairment of Charcot-Marie-Tooth type 2S and the more severe condition of spinal muscular atrophy with respiratory distress type 1 in which infantile respiratory failure predominates.

Methods

We describe the first reported case of spinal muscular atrophy with respiratory distress type 1 caused by a novel deep intronic variant in IGHMBP2 (NM_002180c.712-610A>G).

Results

The variant was detected by whole genome sequencing. Reverse transcription–polymerase chain reaction and complimentary DNA sequencing were used to characterize the impact of the novel variant.

Conclusions

This report illustrates the utility in clinical practice of genome sequencing and RNA analysis, compared with exome sequencing alone.

中文翻译：

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联合基因组测序和 RNA 分析揭示并表征了患有 1 型呼吸窘迫的脊髓性肌萎缩患者的 IGHMBP2 的深层内含子变异

背景

IGHMBP2基因中的致病性变异会导致不同表型的隐性脊髓运动神经病，包括主要为 Charcot-Marie-Tooth 2S 型的远端运动障碍，以及更严重的脊髓性肌萎缩症伴 1 型呼吸窘迫，其中以婴儿呼吸衰竭为主。

方法

我们描述了第一个报告的由IGHMBP2 (NM_002180c.712-610A>G) 中的新型深内含子变异引起的 1 型呼吸窘迫的脊髓性肌萎缩病例。

结果

该变异是通过全基因组测序检测到的。逆转录聚合酶链反应和互补 DNA 测序用于表征新变体的影响。

结论

与单独的外显子组测序相比，本报告说明了基因组测序和 RNA 分析在临床实践中的实用性。