Molecular Analysis of SMN2, NAIP and GTF2H2 Gene Deletions and Relation with Clinical Subtypes of Spinal Muscular Atrophy

Karasu, Nilgun; Acer, Hamit; Akalın, Hilal; Demir, Mikail; Şahin, İzem Olcay; Gökçe, Nuriye; Güleç, Ayten; Ciplakligil, Asli; Sarilar, Ayşe Çağlar; Cüce, İsa; Gümüş, Hakan; Per, Hüseyin; Canpolat, Mehmet; Dündar, Munis

doi:10.21203/rs.3.rs-1442537/v1

Cited by 4 publications

(5 citation statements)

References 31 publications

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“…2023;10(4): [24][25][26][27][28] Molecular genetic analysis of SMA associated genes Turkish population examined the expression levels of SER-F1A, GTF2H2, NCALD, ZPR1, TIA1, PFN2, and CORO1C genes for the first time in SMA patients (Zhuri et al, 2022) showed statistically significant differences ( p = 0.037, p = 0.001) between SERF1A and NAIP genes compared between control group and patients groups [26]. Another study conducted between 2018 and 2021 included 58 SMA patients and 40 healthy individuals as a control group also in Turkish population (Karasu et al, 2022) showed that the genes NAIP (p = 0.0095) and GTF2H2 (p = 0.0049) exhibited a significant difference between healthy subjects and those with SMA [8].…”

Section: Discussionmentioning

confidence: 97%

“…Additionally, prior research in various populations has linked severity to alterations in the NAIP and GTF2H2 genes (Liu et al, 2016) [21]. Additionally, it has been demonstrated that NAIP plays a role in preventing motor neuron apoptosis and is homozygously deleted in approximately 50% of SMA type 1 cases [25], while the GTF2H2 gene is important in transcription and DNA repair [8].…”

Section: Discussionmentioning

confidence: 99%

“…In over 95% of cases, SMA is caused by homozygous deletion of exon 7 in the SMN1 gene [3][4][5]. However, mutations in other genes in the SMA region can contribute to the disease, such as SMN2, NAIP, and GTF2H2 genes [6][7][8].…”

Section: Introductionmentioning

confidence: 99%

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Analysis of SMN1, NAIP and GTF2H2 gene status in correlation with spinal muscular atrophy

Coliban,

Sacara

2023

MJHS

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Introduction. Spinal Muscular Atrophy (SMA) is a genetic disorder caused by the loss of the survival motor neuron (SMN1) gene in over 95% of cases. Additionally, mutations in genes associated with the SMA chromosomal region can influence disease progression. Aim: To analyze the status of the NAIP and GTF2H2 genes in correlation with SMA. Material and methods. The study included 105 patients suspected for SMA of which 50 with confirmed with SMA and 55 without causative deletions, and 107 healthy, unrelated individuals. The molecular genetics methods used were mPCR, PCR-RFLP and MLPA. Results. From 105 patients, 50 were confirmed with SMA. In this group were identified in 8 patients (16%) with a homozygous deletion of exon 5 of the NAIP gene, 4 patients (8%) had a heterozygous status, and 2 (4%) had duplications. In the rest of the patients (55), in which deletions of SMN1 exon 7 were not identified, homozygous deletion of exon 5 of the NAIP gene was established in one patient (2%), 3 patients (5%) had duplications of exon 5 of the NAIP gene, and one patient had 5 copies of the NAIP gene. In the 107 healthy controls, one patient (1%) was identified with a deletion of exon 5 of the NAIP gene. None of the patients with combined deletions of SMN1 and NAIP had deletions in GTF2H2. Conclusions. The frequency of deletions in the NAIP gene was found to be higher in the SMA patient group compared to the control group. Thus, a significant relationship was identified, the P value being <0.00001. The significance threshold was set at p<0.05. The genetic patterning of genes associated with SMA is an important aspect in the study of molecular pathophysiology and assessment of disease prognosis, especially in the approach to gene therapies.

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Section: Discussionmentioning

confidence: 97%

Section: Discussionmentioning

confidence: 99%

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Analysis of SMN1, NAIP and GTF2H2 gene status in correlation with spinal muscular atrophy

Coliban,

Sacara

2023

MJHS

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“…The general transcription factor IIH subunit 2 (GTF2H2) is part of a 500 kb inverted duplication on chromosome 5q13. Duplicated regions often include at least four genes and repetitive elements, which tend to undergo rearrangement and deletion (Karasu et al, 2022).…”

Section: Discussionmentioning

confidence: 99%

Gene expression signature of human neuropathic pain identified through transcriptome analysis

Wang

et al. 2023

Front. Genet.

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Introduction: Neuropathic pain is a type of chronic pain that is characterized by ongoing discomfort and can be challenging to manage effectively. This study aimed to identify genes associated with neuropathic pain through transcriptome analysis in order to gain a better understanding of the mechanisms underlying this chronic, difficult-to-treat pain.Methods: We conducted transcriptome analysis using a training datasetof 202 individuals, including patients with neuropathic pain and healthy controls.Results: Our analysis identified five genes (GTF2H2, KLHL5, LRRC37A4P, PRR24, and MRPL23) that were significantly differentially expressed in the tissue of patients with neuropathic pain compared to controls. We constructed a neuropathic pain signature using these five genes and validated it using an independent dataset of 25 individuals. Receiver operating characteristic (ROC) curve analysis demonstrated that this signature had a high level of accuracy in differentiating between neuropathic pain patients and healthy controls, with an area under the curve (AUC) of 0.83 (95% CI 0.65–1).Discussion: These findings suggest that these five genes may be potential therapeutic targets for neuropathic pain.

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“…Наблюдалась значительная разница между контрольной группой и группой пациентов с делецией NAIP (р = 0,0095) и делецией GTF2H2 (р = 0,0049), но не было обнаружено существенной разницы между подтипами СMA. В исследовании корреляции генотип-фенотип, проведенном на Кипре, было подчеркнуто, что гомозиготная делеция NAIP и GTF2H2 может вызвать тяжелый фенотип у пациентов со СМА 5q [60].…”

Section: модифицирующие факторыunclassified

Factors modifying the course of spinal muscular atrophy 5q

Akhkiamova,

Shchagina,

Polyakov

2024

Neuromuscular Diseases

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Proximal spinal muscular atrophy 5q (SMA 5q) is a severe autosomal recessive neuromuscular disease characterized by progressive symptoms of flaccid paralysis and muscular atrophy due to degeneration of α-motor neurons of the anterior horns of the spinal cord. To date, the main modifying factor of spinal muscular atrophy is considered to be the number of copies of the SMN2 gene. However, a sufficient number of other genetic and non-genetic modifiers of the course of SMA have been described.Advanced neonatal screening, which started in the Russian Federation in 2023, allows detecting SMA 5q before the onset of clinical manifestations. However, to start therapy and select the right drug, it is important to know not only the main modifying factor (the number of copies of SMN2), but also other genetic causes that may affect the age of the disease manifestation or the effectiveness of therapy.

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Molecular Analysis of SMN2, NAIP and GTF2H2 Gene Deletions and Relation with Clinical Subtypes of Spinal Muscular Atrophy

Cited by 4 publications

References 31 publications

Analysis of SMN1, NAIP and GTF2H2 gene status in correlation with spinal muscular atrophy

Analysis of SMN1, NAIP and GTF2H2 gene status in correlation with spinal muscular atrophy

Gene expression signature of human neuropathic pain identified through transcriptome analysis

Factors modifying the course of spinal muscular atrophy 5q

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