Phenotypic and genotypic features of patients diagnosed with ALS in the city of Sakarya, Turkey

Kotan, Dilcan; Ayas, Zeynep Özözen; Tunca, Ceren; Güngen, Belma Doğan; Akçimen, Fulya; Başak, A. Nazlı

doi:10.1007/s13760-020-01441-z

Cited by 4 publications

(4 citation statements)

References 46 publications

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“…Forty‐two related papers [6, 7, 22–61] were summarized and it was found that 178 of 9814 patients with ALS/FTD carried TBK1 variants, including 95 patients carrying LoF variants and 83 patients carrying missense variants (Table S4). Therefore, a meta‐analysis was performed of the frequency of TBK1 variants reported in ALS/FTD patients (Figure 3).…”

Section: Resultsmentioning

confidence: 99%

TBK1 variants in Chinese patients with amyotrophic lateral sclerosis: Genetic analysis and clinical features

Zhao

Jiang

Lin

et al. 2023

Euro J of Neurology

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Background and purposeHaploinsufficiency of TANK‐binding kinase 1 (TBK1) loss‐of‐function (LoF) variants has been shown to be pathogenic in amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). However, the genetic spectrum of TBK1 and clinical features of ALS patients with TBK1 variants remain largely unknown in Asians.MethodsGenetic analysis was performed on 2011 Chinese ALS patients. Software was used to predict the deleteriousness of missense variants in TBK1. In addition, PubMed, Embase and Web of Science were searched for related literature.ResultsTwenty‐six TBK1 variants were identified in 33 of 2011 ALS patients, including six novel LoF variants (0.3%) and 20 rare missense variants, 12 of which were predicted to be deleterious (0.6%). In addition to TBK1 variants, 11 patients had other ALS‐related gene variants. Forty‐two previous studies found that the frequency of TBK1 variants was 1.81% in ALS/FTD patients. The frequency of TBK1 LoF variants in ALS was 0.5% (Asians 0.4%; Caucasian 0.6%) and that of missense variants was 0.8% (Asians 1.0%; Caucasian 0.8%). ALS patients with TBK1 LoF variants affecting the kinase domain had a significantly younger age of onset than patients carrying LoF variants affecting the coiled coil domains CCD1 and CCD2. FTD has a frequency of 10% in Caucasian ALS patients with TBK1 LoF variants, which was not found in our cohort.ConclusionOur study expanded the genotypic spectrum of ALS patients with TBK1 variants and found that the clinical manifestations of TBK1 carriers are diverse.

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Section: Resultsmentioning

confidence: 99%

TBK1 variants in Chinese patients with amyotrophic lateral sclerosis: Genetic analysis and clinical features

Zhao

Jiang

Lin

et al. 2023

Euro J of Neurology

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“…The co-occurrence of FTD, PDB, parkinsonism, myopathy, or psychiatric diseases was commonly seen in the ALS cases carrying VCP mutations (Table 3). The co-existence of FTD or cognitive impairment was found in patients with seven VCP mutations (p.K60R, p.D98V, p.R155C, p.R159G, p.R191Q, p.R191P, and p.R487H) (5,17,44,45,52,56,60), while PDB was diagnosed in ALS patients with six VCP mutations (p.R93C, p.G128A, p.R155C, p.M158V, p.R159G, and p.R159C) (5,6,45,53,56,58). Co-occurrence of myopathy was reported in ALS patients with VCP p.R155C and p.R191G mutations (6,45,56), and psychiatric disorders were found in patients with p.G156C and p.R159G mutations (5,57).…”

Section: Discussionmentioning

confidence: 99%

Phenotype of VCP Mutations in Chinese Amyotrophic Lateral Sclerosis Patients

et al. 2022

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Mutations in the valosin-containing protein (VCP) gene have been linked to amyotrophic lateral sclerosis (ALS) in the Caucasian populations. However, the phenotype of VCP mutations in Chinese patients with (ALS) remains unclear. Targeted next-generation sequencing covered 28 ALS-related genes including the VCP gene was undertaken to screen in a Chinese cohort of 275 sporadic ALS cases and 15 familial ALS pedigrees. An extensive literature review was performed to identify all patients with ALS carrying VCP mutations previously reported. The clinical characteristics and genetic features of ALS patients with VCP mutations were reviewed. One known p.R155C mutation in the VCP gene was detected in two siblings from a familial ALS pedigree and two sporadic individuals. In addition, the same VCP p.R155C mutation was detected in an additional patient with ALS referred in 2021. Three patients with VCP p.R155C mutation presented with muscular weakness starting from proximal extremities to distal extremities. The other patient developed a phenotype of Paget's disease of bone in addition to the progressive muscular atrophy. We reported the first VCP mutation carrier manifesting ALS with Paget's disease of bone in the Chinese population. Our findings expand the phenotypic spectrum of the VCP mutations in Chinese patients with ALS and suggest that ALS patients with VCP p.R155C mutations tend to present with relatively young onset, symmetrical involvement of proximal muscles weakness of arms or legs, and then progressed to distal muscles of limbs.

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“…We performed a literature review on the clinical and genetic characteristics of previously reported ALS‐VCP cases (Table S1), 2,4–7,16,23–33 and illustrated mutation sites in VCP associated with ALS, IBMPFD, and other phenotypes (Figure S1). 2–5,7,16,20–86 A total of 59 cases have been reported, with the disease typically developing in patients in their 40s–50s, and 14 of the 33 cases survived without artificial respiration for more than five years. Given that the epidemiological studies of general ALS suggest that the peak prevalence is observed in patients in their 70s–80s, and that the median survival time is two to four years, 87–91 the ALS‐VCP cases might be characterized by relatively early disease onset and slow disease progression.…”

Section: Discussionmentioning

confidence: 99%

“…We performed a literature review on the clinical and genetic characteristics of previously reported ALS-VCP cases (Table S1), 2,[4][5][6][7]16,[23][24][25][26][27][28][29][30][31][32][33] and illustrated mutation sites in VCP associated with ALS, IBMPFD, and other phenotypes (Figure S1). [2][3][4][5]7,16, A total of 59 cases have been reported, with the disease typically developing in patients in their 40s-50s, and 14 of the 33 cases survived without artificial respiration for more than five years.…”

Section: Pathological Findingsmentioning

confidence: 99%

An autopsy report of a familial amyotrophic lateral sclerosis case carrying VCP Arg487His mutation with a unique TDP‐43 proteinopathy

Matsubara

Izumi

Oda³

et al. 2021

Neuropathology

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We here report an autopsy case of familial amyotrophic lateral sclerosis (ALS) with p.Arg487His mutation in the valosin-containing protein (VCP) gene (VCP), in which upper motor neurons (UMNs) were predominantly involved. Moreover, our patient developed symptoms of frontotemporal dementia later in life and pathologically exhibited numerous phosphorylated transactivation response DNAbinding protein of 43 kDa (p-TDP-43)-positive neuronal cytoplasmic inclusions and short dystrophic neurites with a few lentiform neuronal intranuclear inclusions, sharing the features of frontotemporal lobar degeneration with TDP-43 pathology type A pattern. A review of previous reports of ALS with VCP mutations suggests that our case is unique in terms of its UMN-predominant lesion pattern and distribution of p-TDP-43 pathology. Thus, this case report effectively expands the clinical and pathological phenotype of ALS in patients with a VCP mutation.

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Phenotypic and genotypic features of patients diagnosed with ALS in the city of Sakarya, Turkey

Cited by 4 publications

References 46 publications

TBK1 variants in Chinese patients with amyotrophic lateral sclerosis: Genetic analysis and clinical features

TBK1 variants in Chinese patients with amyotrophic lateral sclerosis: Genetic analysis and clinical features

Phenotype of VCP Mutations in Chinese Amyotrophic Lateral Sclerosis Patients

An autopsy report of a familial amyotrophic lateral sclerosis case carrying VCP Arg487His mutation with a unique TDP‐43 proteinopathy

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