Severe phenotypes of SMARD1 associated with novel mutations of the IGHMBP2 gene and nuclear degeneration of muscle and Schwann cells

Jędrzejowska, Maria; Madej-Pilarczyk, Agnieszka; Fidziańska, Anna; Mierzewska, Hanna; Pronicka, Ewa; Obersztyn, Ewa; Gos, Monika; Pronicki, Maciej; Kmieć, Tomasz; Migdał, Marek; Mierzewska-Schmidt, Magdalena; Walczak-Wojtkowska, Iwona; Konopka, E.; Hausmanowa-Pétrusewicz, I

doi:10.1016/j.ejpn.2013.11.006

Cited by 23 publications

(33 citation statements)

References 23 publications

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“…Moreover, a predominance of the c.1730 T N C (p.L577P) missense mutations in exon 12 and of the nonsense c.1488C N A (p.C496X) and missense c.1478C N T (p.Thr493Ile) mutations in exon 10 was identified. Some authors reported single heterozygous mutations; probably the second mutation was not identified because of limits in gene sequencing approach which was not able to detect complex rearrangement and large deletion [1,9,10,17,28]. Interestingly, SMARD1 forms can display a high variability in their presentations but up to now a clear correlation between the type of mutation and the phenotype has not been assessed.…”

Section: Genetic Background Of Smard1mentioning

confidence: 91%

“…It was reported that SMARD1 can be associated with intrauterine growth delay, prematurity, foot deformities and a weak cry [8,9]. Some patients also presented an involvement of the autonomic and sensory systems [8,9].…”

Section: Neuromuscular and Respiratory Featuresmentioning

confidence: 93%

“…Foot deformities (equinovarus feet), fatty pads over the metacarpophalangeal joints, excessive sweating [9,12] and seizures [13] have also been reported. In some patients limb muscle involvement follows early respiratory failure making the clinical diagnosis more challenging.…”

Section: Neuromuscular and Respiratory Featuresmentioning

confidence: 95%

“…Recently, MRI study has been performed in 5 Polish patients with SMARD1 [9], showing a normal imaging in 4 of these patients, and a mild ventricular asymmetry in one patient.…”

Section: Neuroimagingmentioning

confidence: 97%

“…Some muscular and Schwann cells presented nuclear abnormalities: different shapes of heterochromatin, dark nuclei due to granular condensed chromatin, and nuclear membrane damage with leakage of nucleoplasm forming chromatin blebs [9]. …”

Section: Neuropathological Hallmarksmentioning

confidence: 99%

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The wide spectrum of clinical phenotypes of spinal muscular atrophy with respiratory distress type 1: A systematic review

Porro¹,

Rinchetti²,

Magri³

et al. 2014

Journal of the Neurological Sciences

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Section: Genetic Background Of Smard1mentioning

confidence: 91%

Section: Neuromuscular and Respiratory Featuresmentioning

confidence: 93%

Section: Neuromuscular and Respiratory Featuresmentioning

confidence: 95%

“…Recently, MRI study has been performed in 5 Polish patients with SMARD1 [9], showing a normal imaging in 4 of these patients, and a mild ventricular asymmetry in one patient.…”

Section: Neuroimagingmentioning

confidence: 97%

Section: Neuropathological Hallmarksmentioning

confidence: 99%

See 3 more Smart Citations

The wide spectrum of clinical phenotypes of spinal muscular atrophy with respiratory distress type 1: A systematic review

Porro¹,

Rinchetti²,

Magri³

et al. 2014

Journal of the Neurological Sciences

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No Evidence for Association of SCO2 Heterozygosity with High-Grade Myopia or Other Diseases with Possible Mitochondrial Dysfunction

Piekutowska‐Abramczuk

Kocyła-Karczmarewicz

Małkowska

et al. 2015

JIMD Reports

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SCO2 mutations cause recessively inherited cytochrome c oxidase deficiency. Recently Tran-Viet et al. proposed that heterozygosity for pathogenic SCO2 variants, including the common E140K variant, causes high-grade myopia. To investigate the association of SCO2 mutations with myopia, ophthalmic examinations were performed on 35 E140K carriers, one homozygous infant, and on a mouse model of Sco2 deficiency. Additionally, a screen for other putative effects of SCO2 heterozygosity was carried out by comparing the prevalence of the common E140K variant in a population of patients with undiagnosed diseases compatible with SCO2-related pathogenesis to that in a general population sample. High-grade myopia was not identified in any of the studied individuals. Of the carriers, 17 were emmetropic, and 18 possessed refractive errors. Additionally, no significant axial elongation indicative of high-grade myopia was found in mice carrying E129K (corresponding to E140K in humans) knock-in mutations. The prevalence of E140K carriers in the symptomatic cohort was evaluated as 1:103 (CI: 0.44-2.09) and did not differ significantly from the population prevalence (1:147, CI: 0.45-1.04).Our study demonstrates that heterozygosity for pathogenic SCO2 variants is not associated with high-grade myopia in either human patients or in mice.

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Current understanding of and emerging treatment options for spinal muscular atrophy with respiratory distress type 1 (SMARD1)

Perego

Galli

Nizzardo

et al. 2020

Cell. Mol. Life Sci.

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Spinal muscular atrophy (SMA) with respiratory distress type 1 (SMARD1) is an autosomal recessive motor neuron disease that is characterized by distal and proximal muscle weakness and diaphragmatic palsy that leads to respiratory distress. Without intervention, infants with the severe form of the disease die before 2 years of age. SMARD1 is caused by mutations in the IGHMBP2 gene that determine a deficiency in the encoded IGHMBP2 protein, which plays a critical role in motor neuron survival because of its functions in mRNA processing and maturation. Although it is rare, SMARD1 is the second most common motor neuron disease of infancy, and currently, treatment is primarily supportive. No effective therapy is available for this devastating disease, although multidisciplinary care has been an essential element of the improved quality of life and life span extension in these patients in recent years. The objectives of this review are to discuss the current understanding of SMARD1 through a summary of the presently known information regarding its clinical presentation and pathogenesis and to discuss emerging therapeutic approaches. Advances in clinical care management have significantly extended the lives of individuals affected by SMARD1 and research into the molecular mechanisms that lead to the disease has identified potential strategies for intervention that target the underlying causes of SMARD1. Gene therapy via gene replacement or gene correction provides the potential for transformative therapies to halt or possibly prevent neurodegenerative disease in SMARD1 patients. The recent approval of the first gene therapy approach for SMA associated with mutations in the SMN1 gene may be a turning point for the application of this strategy for SMARD1 and other genetic neurological diseases.

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Severe phenotypes of SMARD1 associated with novel mutations of the IGHMBP2 gene and nuclear degeneration of muscle and Schwann cells

Cited by 23 publications

References 23 publications

The wide spectrum of clinical phenotypes of spinal muscular atrophy with respiratory distress type 1: A systematic review

The wide spectrum of clinical phenotypes of spinal muscular atrophy with respiratory distress type 1: A systematic review

No Evidence for Association of SCO2 Heterozygosity with High-Grade Myopia or Other Diseases with Possible Mitochondrial Dysfunction

Current understanding of and emerging treatment options for spinal muscular atrophy with respiratory distress type 1 (SMARD1)

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