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- Hikmat, O., et al.
(författare)
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Simplifying the clinical classification of polymerase gamma (POLG) disease based on age of onset; studies using a cohort of 155 cases
- 2020
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Ingår i: Journal of Inherited Metabolic Disease. - : Wiley. - 0141-8955 .- 1573-2665. ; 43:4, s. 726-736
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Tidskriftsartikel (refereegranskat)abstract
- Background: Variants in POLG are one of the most common causes of inherited mitochondrial disease. Phenotypic classification of POLG disease has evolved haphazardly making it complicated and difficult to implement in everyday clinical practise. The aim of our study was to simplify the classification and facilitate better clinical recognition. Methods: A multinational, retrospective study using data from 155 patients with POLG variants recruited from seven European countries. Results: We describe the spectrum of clinical features associated with POLG variants in the largest known cohort of patients. While clinical features clearly form a continuum, stratifying patients simply according to age of onset—onset prior to age 12 years; onset between 12 and 40 years and onset after the age of 40 years, permitted us to identify clear phenotypic and prognostic differences. Prior to 12 years of age, liver involvement (87%), seizures (84%), and feeding difficulties (84%) were the major features. For those with onset between 12 and 40 years, ataxia (90%), peripheral neuropathy (84%), and seizures (71%) predominated, while for those with onset over 40 years, ptosis (95%), progressive external ophthalmoplegia (89%), and ataxia (58%) were the major clinical features. The earlier the onset the worse the prognosis. Patients with epilepsy and those with compound heterozygous variants carried significantly worse prognosis. Conclusion: Based on our data, we propose a simplified POLG disease classification, which can be used to guide diagnostic investigations and predict disease course. © 2020 The Authors. Journal of Inherited Metabolic Disease published by John Wiley & Sons Ltd on behalf of SSIEM
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- Hikmat, O., et al.
(författare)
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The impact of gender, puberty, and pregnancy in patients with POLG disease
- 2020
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Ingår i: Annals of Clinical and Translational Neurology. - : Wiley. - 2328-9503. ; 7:10, s. 2019-2025
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Tidskriftsartikel (refereegranskat)abstract
- Objective To study the impact of gender, puberty, and pregnancy on the expression of POLG disease, one of the most common mitochondrial diseases known. Methods Clinical, laboratory, and genetic data were collected retrospectively from 155 patients with genetically confirmed POLG disease recruited from seven European countries. We used the available data to study the impact of gender, puberty, and pregnancy on disease onset and deterioration. Results We found that disease onset early in life was common in both sexes but there was also a second peak in females around the time of puberty. Further, pregnancy had a negative impact with 10 of 14 women (71%) experiencing disease onset or deterioration during pregnancy. Interpretation Gender clearly influences the expression of POLG disease. While onset very early in life was common in both males and females, puberty in females appeared associated both with disease onset and increased disease activity. Further, both disease onset and deterioration, including seizure aggravation and status epilepticus, appeared to be associated with pregnancy. Thus, whereas disease activity appears maximal early in life with no subsequent peaks in males, both menarche and pregnancy appear associated with disease onset or worsening in females. This suggests that hormonal changes may be a modulating factor.
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- Leich, E., et al.
(författare)
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Gene expression and copy number profiling of follicular lymphoma biopsies from patients treated with first-line rituximab without chemotherapy
- 2023
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Ingår i: Leukemia and Lymphoma. - : Taylor & Francis. - 1042-8194 .- 1029-2403. ; 64:12, s. 1927-1937
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Tidskriftsartikel (refereegranskat)abstract
- The Nordic Lymphoma Study Group has performed two randomized clinical trials with chemotherapy-free first-line treatment (rituximab +/- interferon) in follicular lymphoma (FL), with 73% of patients alive and 38% without any need of chemotherapy after 10.6 years median follow-up. In order to identify predictive markers, that may also serve as therapeutic targets, gene expression- and copy number profiles were obtained from 97 FL patients using whole genome microarrays. Copy number alterations (CNAs) were identified, e.g. by GISTIC. Cox Lasso Regression and Lasso logistic regression were used to determine molecular features predictive of time to next therapy (TTNT). A few molecular changes were associated with TTNT (e.g. increased expression of INPP5B, gains in 12q23/q24), but were not significant after adjusting for multiple testing. Our findings suggest that there are no strong determinants of patient outcome with respect to GE data and CNAs in FL patients treated with a chemotherapy-free regimen (i.e. rituximab +/- interferon).
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