Mutation analysis of SOD1, C9orf72, TARDBP and FUS genes in ethnically-diverse Malaysian patients with amyotrophic lateral sclerosis (ALS)

Edgar, Suzanna; Ellis, Melina; Abdul-Aziz, Nur Adilah; Goh, Khean Jin; Shahrizaila, Nortina; Kennerson, Marina; Ahmad‐Annuar, Azlina

doi:10.1016/j.neurobiolaging.2021.07.008

Cited by 14 publications

(4 citation statements)

References 47 publications

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“…The bottom part shows the list of c9orf72 sALS and fALS cases in Eurasian countries reported before. 11,[13][14][15][16][17][18][19][20][21][22][23][24][25][26] This figure is an original figure produced by the authors for this article. ALS, Amyotrophic lateral sclerosis; sALS, sporadic ALS; fALS, familial ALS.…”

Section: Resultsmentioning

confidence: 99%

Analysis of C9orf72 repeat expansions in Georgian patients with Amyotrophic lateral sclerosis (ALS)

Kekenadze,

Rocca,

Turchetti

et al. 2024

F1000Res

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Background Amyotrophic lateral sclerosis (ALS) is a fatal progressive neurodegenerative disorder that affects the upper and lower motor neurons. Several genetic risk factors have been identified in the past decade with a hexanucleotide repeat expansion in the C9orf72 gene being the most significant. However, the presence of C9orf72 repeat expansion has not been examined in the Transcaucasian region, therefore we aimed to analyse its frequency in Georgian patients with ALS. Methods We included 64 self-reported Georgian patients with ALS from different parts of the country, fulfilling the Gold Coast criteria. To investigate the presence of an expanded GGGGCC hexanucleotide repeat in the non-coding region of the C9orf72 gene, we performed Repeat-Primed PCR (RP-PCR). Results In total, 62 sporadic and two familial ALS cases were identified. Patients were aged 26 to 84 years with a mean age of 58.3 years at disease onset. Bulbar onset was observed in 21.88%, upper limb onset in 34.38%, and lower limb onset in 43.75% of the patients. Frontotemporal dementia (FTD) fulfilling the Strong criteria was diagnosed in seven patients (10.94%). C9orf72 repeat expansion was detected in only one case using RP-PCR; the patient had a family history of dementia. Conclusions Our results indicate that C9orf72 hexanucleotide expansion does not belong to the major genetic risk factor of ALS in Georgian patients. Further genetic studies in a bigger study population are needed to reveal the genetic causes of ALS in the Transcaucasian population.

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Section: Resultsmentioning

confidence: 99%

Analysis of C9orf72 repeat expansions in Georgian patients with Amyotrophic lateral sclerosis (ALS)

Kekenadze,

Rocca,

Turchetti

et al. 2024

F1000Res

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“…The occurrence of these three genes (SOD1, TARDBP, and FUS) are reported inconsistently in ALS in different studies. For example, in two GWAS analysis, deleterious variants of the three genes (SOD1, TARDBP, and FUS) were found to be absent (Edgar S, et al, 2021;, Restuadi R, et al, 2022), despite being reported in other studies (Benatar M, et al,2022;Goutman SA, et al, 2022). This inconsistency may be caused by disparities in race, region, or sample characteristics.…”

Section: Discussionmentioning

confidence: 98%

No cause-effect relationships between psychiatric disorders and amyotrophic lateral sclerosis: a bidirectional Mendelian randomization study

Huang

Wen

Tian

et al. 2023

Preprint

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Background Previous reports have been inconsistent about the associations between amyotrophic lateral sclerosis (ALS) and psychiatric disorders. More importantly, it needs to be elucidated whether these associations are causal or confounded. Objective We aimed to determine the presence of cause-effect relationships between ALS and four psychiatric disorders (schizophrenia; bipolar disorder; anxiety, nerves, tension or depression disorders (ADD); and neuroticism) using a bidirectional Mendelian randomization (BDMR) analysis based on gene associations. Methods First, we extracted genome-wide association studies (GWAS) summaries for the four psychiatric disorders and ALS from the Integrative Epidemiology Unit (IEU) and the Psychiatric Genomics Consortium (PGC) GWAS database. We then identified single-nucleotide polymorphisms (SNPs) that are strongly associated with exposure, are independent of confounders, and are related to exposure-outcome, as instrumental variables (IVs) for Mendelian randomization (MR) analyses. In the MR analysis, the cause-effect relationships were analyzed using psychiatric disorders as the exposure variable and ALS as the outcome, with six methods (primary inverse-variance weighted (IVW), MR-Egger, weighted median estimator, simple mode, weighted mode, and robust adjusted profile score (RAPS)analyses). Moreover, the results were subjected to sensitivity analyses, namely, IVW and MR-Egger analyses (for potential heterogeneity and horizontal pleiotropy) and MR leave-one-out analysis (to determine whether one SNP drove the causal signal). Finally, reverse MR analyses were conducted using ALS as the exposure variable and four psychiatric disorders as outcome variables; sensitivity was assessed. Results After extracting the GWAS summaries, we established IVs, including 147, 13, 37, and 105 SNPs for schizophrenia, bipolar disorder, ADD, and neuroticism, respectively. Subsequently, the MR analyses conducted using the six methods revealed no cause-effect relationships of the four psychiatric disorders with ALS. Moreover, we set up six SNPs as IVs for ALS in reverse MR analyses. Finally, no statistically significant cause-effect relationship of ALS with the four psychiatric disorders was found. These associations were robust as shown by the sensitivity analyses. Conclusions BDMR analyses revealed no significant genetic evidence for a cause-effect relationship between ALS and four psychiatric disorders.

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“…To date, more than 30 genes have been implicated in a reproducible way, while more than 120 have been proposed as potentially related to ALS, although most still have uncertain significance and often have not been replicated. Epigenetic influences may also play an important role 6 . The genetic causality of ALS is even greater the lower the age of onset (known as a juvenile form when you have a debut under 25 years).…”

Section: Discussionmentioning

confidence: 99%

Amyotrophic Lateral Sclerosis as a phenotypic form of the SPG11 gene mutation spectrum. A case report.

León-Castillo,

Bertado-Cortés,

Gutiérrez-Guzmán

et al. 2023

HGMX

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Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease that affects to both the upper and lower motor neuron. We reported a rare presentation of ALS with SPG11 mutation with heterozygous state, contrary to the classic autosomal recessive form of ALS associated with this mutation, thus documenting the third case found with probable association with said pattern of inheritance, and the first of related ALS a mutation of SPG11 in Mexico. This allows us to reaffirm the genetic heterogeneity of ALS and the prognostic importance of the determination of such rare mutations with less lethal course to the classical form.

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Mutation analysis of SOD1, C9orf72, TARDBP and FUS genes in ethnically-diverse Malaysian patients with amyotrophic lateral sclerosis (ALS)

Cited by 14 publications

References 47 publications

Analysis of C9orf72 repeat expansions in Georgian patients with Amyotrophic lateral sclerosis (ALS)

Analysis of C9orf72 repeat expansions in Georgian patients with Amyotrophic lateral sclerosis (ALS)

No cause-effect relationships between psychiatric disorders and amyotrophic lateral sclerosis: a bidirectional Mendelian randomization study

Amyotrophic Lateral Sclerosis as a phenotypic form of the SPG11 gene mutation spectrum. A case report.

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