Expanding the genotype–phenotype correlation of childhood sensory polyneuropathy of genetic origin

Chakravorty, Samya; Logan, Rachel; Elson, Molly J.; Luke, Rebecca R.; Verma, Sumit

doi:10.1038/s41598-020-73219-5

Cited by 6 publications

(5 citation statements)

References 93 publications

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“… Absence of family history of A-T was documented in at least 60 cases (54 studies [ 21 , 50 , 65 , 80 , 86 , 95 , 98 , 111 , 122 , 134 , 135 , 150 , 155 , 181 , 188 , 190 , 197 , 202 , 203 , 222 , 224 , 236 , 238 , 239 , 242 , 252 , 254 , 255 , 267 , 272 – 274 , 276 , 366 , 379 – 398 ]). …”

Section: Resultsmentioning

confidence: 99%

“…62 cases (27 studies [ 33 , 38 , 41 , 49 , 53 , 55 , 72 , 118 , 120 , 123 , 139 , 143 , 186 , 208 , 212 , 213 , 338 , 358 , 366 , 368 , 372 , 388 , 392 , 519 , 528 , 683 , 684 ]) reported an abnormal EMG. The youngest age at which an abnormal EMG was reported was 4 years 0 months.…”

Section: Resultsmentioning

confidence: 99%

“…294 cases (80 studies [ 18 , 23 , 24 , 42 , 52 – 54 , 61 , 66 , 75 , 76 , 80 , 84 , 88 , 91 , 101 , 104 , 108 , 111 , 166 , 175 , 179 , 190 , 194 , 212 , 217 , 221 , 224 , 225 , 228 , 230 , 231 , 236 , 239 , 242 , 244 , 248 , 254 , 259 , 270 , 271 , 274 , 289 , 290 , 315 , 331 , 347 , 366 , 372 , 384 , 394 , 401 , 403 , 406 , 414 , 426 ,…”

Section: Resultsunclassified

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The natural history of ataxia-telangiectasia (A-T): A systematic review

et al. 2022

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Background Ataxia-telangiectasia is an autosomal recessive, multi-system, and life-shortening disease caused by mutations in the ataxia-telangiectasia mutated gene. Although widely reported, there are no studies that give a comprehensive picture of this intriguing condition. Objectives Understand the natural history of ataxia-telangiectasia (A-T), as reported in scientific literature. Search methods 107 search terms were identified and divided into 17 searches. Each search was performed in PubMed, Ovid SP (MEDLINE) 1946-present, OVID EMBASE 1980 –present, Web of Science core collection, Elsevier Scopus, and Cochrane Library. Selection criteria All human studies that report any aspect of A-T. Data collection and analysis Search results were de-duplicated, data extracted (including author, publication year, country of origin, study design, population, participant characteristics, and clinical features). Quality of case-control and cohort studies was assessed by the Newcastle-Ottawa tool. Findings are reported descriptively and where possible data collated to report median (interquartile range, range) of outcomes of interest. Main results 1314 cases reported 2134 presenting symptoms. The most common presenting symptom was abnormal gait (1160 cases; 188 studies) followed by recurrent infections in classical ataxia-telangiectasia and movement disorders in variant ataxia-telangiectasia. 687 cases reported 752 causes of death among which malignancy was the most frequently reported cause. Median (IQR, range) age of death (n = 294) was 14 years 0 months (10 years 0 months to 23 years 3 months, 1 year 3 months to 76 years 0 months). Conclusions This review demonstrates the multi-system involvement in A-T, confirms that neurological symptoms are the most frequent presenting features in classical A-T but variants have diverse manifestations. We found that most individuals with A-T have life limited to teenage or early adulthood. Predominance of case reports, and case series demonstrate the lack of robust evidence to determine the natural history of A-T. We recommend population-based studies to fill this evidence gap.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsunclassified

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The natural history of ataxia-telangiectasia (A-T): A systematic review

et al. 2022

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“…Although 29 patients have been reported to date, only 10 pathogenic COX20 gene mutations have been identified. Among the 29 patients, 3 Turkish patients from 2 unrelated families were all reported to carry the same pathogenic homozygous mutation (c.154 A > C, pT52p) [ 5 , 8 ]; one Turkish patient carried a homozygous mutation (c.190 A > C, pT4P) [ 9 ]; 6 American patients from 4 unrelated families all carried the same compound heterozygous mutations (c.41 A > G, c.157 + 3G > C) [ 7 , 10 ], and the other 19 patients from China all carried the frequently observed c.41 A > G (p.Lys14Arg) mutation, which occurred as a homozygous and compound heterozygous variant. It appears that distinct hot spot mutations of COX20 gene were presented in diverse regions and the population at risk is Chinese.…”

Section: Discussionmentioning

confidence: 99%

Clinical and genetic characteristics of children with COX20-associated mitochondrial disorder: case report and literature review

Chen

Liu

2023

BMC Med Genomics

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Background The deficiency of cytochrome c oxidase 20 is a rare autosomal recessive mitochondrial disorder characterized by ataxia, dysarthria, dystonia and sensory neuropathy. Case presentation In this study, we describe a patient from a non-consanguineous family exhibiting developmental delay, ataxia, hypotonia, dysarthria, strabismus, visual impairment and areflexia. An examination of nerve conduction showed a normal result at first but revealed axonal sensory neuropathy later. This situation has not been reported in any literatures. The whole-exome sequencing analysis revealed that the patient harbored compound heterozygous mutations (c.41 A > G and c.259G > T) of the COX20 gene. By literature review, 5 patients carried the same compound heterozygous mutations. Conclusion COX20 might be considered as a potential gene for the early-onset ataxia and the axonal sensory neuropathy. Our patient exhibited strabismus and visual impairment, which expands the clinical presentation of COX20 related mitochondrial disorders caused by the compound heterozygous variants (c.41 A > G and c.259G > T). However, a clear genotype/phenotype correlation has not yet been established. Additional researches and cases are needed to further confirm the correlation.

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“…Upregulated acetylated proteins in the pathway of fatty acids metabolism were HADHA, ACOT7, ALDH9A1, and GOT2. HADHA-related mitochondrial trifunctional protein deficiency was detected in one childhood sensory polyneuropathy with refractory seizures ( 48 ). Neurons antagonize fatty acid utilization by hydrolyzing long chain acyl-CoAs (activated form of fatty acids) via acyl-CoA thioesterase 7 (ACOT7) ( 49 ).…”

Section: Discussionmentioning

confidence: 99%

Acetylation Profiles in the Metabolic Process of Glioma-Associated Seizures

Lin

Zheng

et al. 2021

Front. Neurol.

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Objective: We test the hypothesis that lysine acetylation is involved in the metabolic process of glioma-associated seizures (GAS).Methods: We used label-free mass spectrometry-based quantitative proteomics to quantify dynamic changes of protein acetylation between gliomas with seizure (CA1 group) and gliomas without seizure (CA2 group). Furthermore, differences of acetyltransferase and deacetylase expression between CA1 and CA2 groups were performed by a quantitative proteomic study. We further classified acetylated proteins into groups according to cell component, molecular function, and biological process. In addition, metabolic pathways and protein interaction networks were analyzed. Regulated acetyltransferases and acetylated profiles were validated by PRM and Western blot.Results: We detected 169 downregulated lysine acetylation sites of 134 proteins and 39 upregulated lysine acetylation sites of 35 proteins in glioma with seizures based on acetylome. We detected 407 regulated proteins by proteomics, from which ACAT2 and ACAA2 were the differentially regulated enzymes in the acetylation of GAS. According to the KEGG analysis, the upregulated acetylated proteins within the PPIs were mapped to pathways involved in the TCA cycle, oxidative phosphorylation, biosynthesis of amino acids, and carbon metabolism. The downregulated acetylated proteins within the PPIs were mapped to pathways involved in fatty acid metabolism, oxidative phosphorylation, TCA cycle, and necroptosis. Regulated ACAT2 expression and acetylated profiles were validated by PRM and Western blot.Conclusions: The data support the hypothesis that regulated protein acetylation is involved in the metabolic process of GAS, which may be induced by acetyl-CoA acetyltransferases.

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Expanding the genotype–phenotype correlation of childhood sensory polyneuropathy of genetic origin

Cited by 6 publications

References 93 publications

The natural history of ataxia-telangiectasia (A-T): A systematic review

The natural history of ataxia-telangiectasia (A-T): A systematic review

Clinical and genetic characteristics of children with COX20-associated mitochondrial disorder: case report and literature review

Acetylation Profiles in the Metabolic Process of Glioma-Associated Seizures

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