Exploring the relationship between IGHMBP2 gene mutations and spinal muscular atrophy with respiratory distress type 1 and Charcot-Marie-Tooth disease type 2S: a systematic review

Abstract

BackgroundIGHMBP2 is a crucial gene for the development and maintenance of the nervous system, especially in the survival of motor neurons. Mutations in this gene have been associated with spinal muscular atrophy with respiratory distress type 1 (SMARD1) and Charcot-Marie-Tooth disease type 2S (CMT2S).MethodsWe conducted a systematic literature search using the PubMed database to identify studies published up to April 1st, 2023, that investigated the association between IGHMBP2 mutations and SMARD1 or CMT2S. We compared the non-truncating mutations and truncating mutations of the IGHMBP2 gene and selected high-frequency mutations of the IGHMBP2 gene.ResultsWe identified 52 articles that investigated the association between IGHMBP2 mutations and SMARD1/CMT2S. We found 6 hotspot mutations of the IGHMBP2 gene. The truncating mutations in trans were all associated with SMARD1.ConclusionThis study provides evidence that the complete LOF mechanism of the IGHMBP2 gene defect may be an important cause of SMARD1.

Electrophysiological and radiological diagnosis of hereditary motor and sensory polyneuropathy

“…Diffuse white matter hyperintense signals in the posterior white matter, centrum semiovale, and corpus callosum of a child mimicking leukodystrophy have also been mentioned in the literature. [ 14 ] Depending on the region of the diseased nerve, MRI may show indirect signs of denervation myopathy, which is a part of many other neuropathies as well. It includes T2 or short tau inversion recovery hyperintense signals of muscles due to muscle edema in the acute phase, followed by muscle atrophy and T1 hyperintense fatty infiltration in the chronic stage.…”

Disease Mechanisms and Therapeutic Approaches in SMARD1—Insights from Animal Models and Cell Models

“…IGHMBP2 mutations in SMARD1 patients are mainly missense mutations in the helicase domain. In contrast, in CMT2S, the mutations were primarily a combination of a nonsense mutation in the 5 ′ region of the gene, with truncating frameshift, missense, or homozygous frameshift mutations in the last exon [5]. Finally, different combinations of mutations in the two diseases resulted in different levels of residual protein.…”

“…The current prevalence is unknown. The symptoms of SMARD1 are caused by mutations in the IGHMBP2 gene (Figure 1A), which encodes for a 5 ′ →3 ′ RNA helicase/ATPase [4] and ultimately results in the loss of helicase function [5]. This corresponds to dysfunction, degeneration, and loss of α-motoneurons in the ventral horn of the spinal cord, which ultimately leads to atrophy of skeletal muscle fibers in the extremities, trunk, and diaphragm [6].…”

“…Recently, mutations in IGHBMBP2 have been described in an axonal form of Charcot-Marie-Tooth (CMT), classified as CMT type 2S (CMT2S) [5,[15][16][17][18][19][20][21] (Figure 1A). CMT2S is a sensorimotor axonal polyneuropathy with normal or near-normal nerve conduction velocity (NCV).…”

“…Tian and colleagues have summarized the proportion of IGHMBP2 gene variants in SMARD1 and CMT2S. Non-truncating mutations in the RecA-like domains (1A and 2A) are hotspots for SMARD1, whereas truncating mutations in the last exon are hotspots for CMT2S [5]. However, Tran and colleagues have recently identified an IGHMBP2 mutation that leads to either SMARD1 or CMT2S, suggesting that the individual genetic background with potential disease-modifying regions plays a critical role in the expression of SMARD1 or CMTS2 [23].…”