5 research outputs found
Correction:Comprehensive genetic screening of early-onset dementia patients in an Austrian cohort-suggesting new disease-contributing genes (Human Genomics, (2023), 17, 1, (55), 10.1186/s40246-023-00499-z)
Following publication of the original article [1], the authors reported an error in Table 1. The correct Table 1 has been provided in this Correction. (Table presented.) Basic clinical and genetic characteristics of all 60 EOD patients ID Diagnosis AAO (years) Sex FH APOE Gene Variant Position Transcript CADD ClinVar Significance for disease EOD-1 EOD-2 c.184G > A; p.R62C chr6:41129208-41129208 NM_001271821.1 25.5 n.r Risk modifier Risk modifier EOD-3 AD 45 f 2 E3/E3 EOD-4 AD 51 f 4 E4/E3 Risk modifier EOD-5 nfPPA 58 f 2 E3/E2 EOD-6 AD 56 f 3 E3/E3 EOD-7 AD/PCA 56 f 4 E3/E3 EOD-8 bvFTD 56 m 4 E3/E3 c.1427T > C; p.M476T chr11:117160361-117160361 NM_012104.3 26.4 n.r Unknown c.9757A > G; p.S3253G chr15:62173781-62173781 NM_020821.2 29.5 n.r Unknown EOD-9 AD 55 f 3,5 E4/E3 Risk modifier EOD-10 AD 58 f 3,5 E3/E3 EOD-11 AD 63 m 4 E3/E3 EOD-12 mixed dementia (AD + VD) 55 m 3,5 E4/E3 Risk modifier EOD-13 AD 61 m 4,5 E3/E3 EOD-14 AD/lpPPA 61 m 4 E4/E3 Risk modifier c.4300C > T; p.V1434I chr15:62244179-62244179 NM_020821.2 24.8 n.r Unknown EOD-15 nfPPA 64 m 2 E3/E3 c.2218C > T; p.E740K chr2:74594514-74594514 NM_004082.4 24.0 n.r Unknown EOD-16 AD 56 f 4 E3/E3 EOD-17 AD (PD) 60 m 1 E4/E3 Risk modifier g.chr16:1816528 A > G; c.2817-2A > G chr16:1816528-1816528 NM_015133.3 22.3 n.r Unknown EOD-18a c.2914C > T; p.P972S chr19:1051537-1051537 NM_019112.3 25.3 n.r Potential risk modifier EOD-19 EOD-19 (2)b EOD-20 AD 57 m 4,5 E3/E3 c.7397T > A; p.L2466H chr12:40760814-40760814 NM_198578.3 25.7 VUS Unknown EOD-21 EOD-22 EOD-23 EOD-24 EOD-25 EOD-26 AD 56 f 4 E3/E3 c.2980G > C; p.P994A chr2:74590268-74590268 NM_023019.3 17.3 VUS Unknown c.2087G > A; p.R696H chr16:1814180-1814180 NM_015133.3 31.0 n.r Unknown EOD-27 AD 57 f 4 E4/E3 Risk modifier EOD-28 AD 54 m 4 E3/E3 EOD-29 AD 54 m 4 E3/E3 EOD-30 AD 64 m 4 E3/E3 EOD-31 mixed dementia (AD + VD) 58 m 3,5 E3/E3 EOD-32 FTD/svPPA 61 m 4 E3/E3 EOD-33 AD 62 f 4,5 E4/E3 Risk modifier c.521G > A; p.S174L chr2:74598788-74598788 NM_004082.4 24.4 VUS Unknown EOD-34 AD 59 f 2 E4/E3 Risk modifier EOD-35 AD 55 m 3,5 E4/E3 Risk modifier EOD-36c AD 64 m 2 E4/E3 c.140G > A; p.R47H chr6:41129252-41129252 NM_018965.3 9.7 LB Risk modifier Risk modifier EOD-37 AD 52 f 3,5 E3/E3 c.7397T > A; p.L2466H chr12:40760814-40760814 NM_198578.3 25.7 VUS Unknown EOD-38 AD 52 f 3,5 E4/E3 Risk modifier EOD-39 AD 63 f 3 E4/E3 Risk modifier EOD-40 AD 55 f 4 E4/E3 Risk modifier EOD-41 AD 58 m 3,5 E3/E3 EOD-42 AD 39 m 4 E3/E2 EOD-43 AD 63 m 4 E3/E3 c.3148A > G; p.I1050V chr15:62256964-62256964 NM_020821.2 0.001 VUS Unknown EOD-44 AD/lpPPA 58 f 3,5 E3/E3 c.3014T > G; p.M1005R chr11:121430331-121430331 NM_003105.5 27.9 n.r Potential risk modifier EOD-45 AD 65 m 4 E3/E3 EOD-46 CBS + AD 51 f 3,5 E3/E3 c.4606G > A; p.G1536S chr11:121474988-121474988 NM_003105.5 25.2 B Risk modifier EOD-47 AD 54 f 4 E3/E3 EOD-48 bvFTD 57 m 4 E3/E3 EOD-49 FTD/nfPPA + ALS 58 m 4 E3/E3 c.986T > C; p.L276P chr12:64875636-64875636 NM_013254.3 n.r Potential risk modifier c.7436T > C; p.I2429T chr15:62212307-62212307 NM_020821.2 n.r Unknown EOD-50 Risk modifier EOD-51 FTD/svPPA 62 f 4 E3/E3 EOD-52 AD 57 m 4 E4/E3 Risk modifier EOD-53 c.7377G > A; p.M2459I chr12:40758839-40758839 NM_198578.3 17.7 n.r Unknown EOD-54 AD 59 m 1 E4/E3 Risk modifier EOD-55 AD 49 m 4 E3/E3 EOD-56 AD 61 m 3,5 E3/E3 EOD-57 AD/lpPPA 57 f 4 E3/E3 EOD-58 AD + VD 64 f 3 E3/E3 c.823C > T; p.R141C chr2:74598126-74598126 NM_004082.3 29.3 VUS Unknown EOD-59 bvFTD 52 m 4 E4/E3 Risk modifier EOD-60 a, EOD-18: The APP duplication of was confirmed to be 'de novo'. Both parents did not show this duplication b, EOD-19 (2) is the brother of EOD19. He was also affected by AD and carrier of the same duplication. EOD 19 (2) was not included in the analyses of AAO and FH c, EOD-36: ClinVar assessment of TREM2 p.R47H of LB (likely benign) refers to Nasu-Hakola disease. However, p.R47H is an established risk variant for dementia (Ref. 15) The original article [1] has been corrected.</p
Comprehensive genetic screening of early-onset dementia patients in an Austrian cohort-suggesting new disease-contributing genes
Mortality and Epidemiological Changes in Proximal Hip Fractures in the Course of a Pandemic
Background: Coronavirus disease 2019 (COVID-19) has had an immense impact on the treatment protocols of orthopedic and trauma departments, yet its specific effect on mortality in patients with hip fractures due to possible surgical delays is still unclear. The purpose of this paper was to investigate whether the COVID-19 pandemic worsened the mortality rate of hip fracture patients. Patients and methods: This study comprised 175 prospectively included patients who (1) suffered from hip fractures, (2) presented during the Austrian state of emergency period from 15 March 2020 to 30 May 2021, and (3) were admitted to a level I trauma center. This cohort was compared with a retrospective control group of 339 patients admitted for hip fractures during the same timeframe in 2017, 2018, and 2019. Results: An admission reduction of 22% in the COVID period compared with the pre-COVID period was evident (p = 0.018). The 30-day mortality rate was 14.67% (pre-COVID) compared with 15.18% (p = 0.381). No differences in surgical complication rates or relationships between comorbidity burden and survival were observed. There were no significant changes in demographic variables, except for admission rate, gender (p = 0.013), and place of accident (p = 0.049). Conclusion: Surgeons should be reassured to take COVID-19 precautions, as this study did not show higher perioperative mortality due to COVID-19 measures. Under the current circumstances, with possibly reduced surgical and hospital bed capacities, it is expected that hip fractures may continue to require a high degree of resources
Mortality and Epidemiological Changes in Proximal Hip Fractures in the Course of a Pandemic
Background: Coronavirus disease 2019 (COVID-19) has had an immense impact on the treatment protocols of orthopedic and trauma departments, yet its specific effect on mortality in patients with hip fractures due to possible surgical delays is still unclear. The purpose of this paper was to investigate whether the COVID-19 pandemic worsened the mortality rate of hip fracture patients. Patients and methods: This study comprised 175 prospectively included patients who (1) suffered from hip fractures, (2) presented during the Austrian state of emergency period from 15 March 2020 to 30 May 2021, and (3) were admitted to a level I trauma center. This cohort was compared with a retrospective control group of 339 patients admitted for hip fractures during the same timeframe in 2017, 2018, and 2019. Results: An admission reduction of 22% in the COVID period compared with the pre-COVID period was evident (p = 0.018). The 30-day mortality rate was 14.67% (pre-COVID) compared with 15.18% (p = 0.381). No differences in surgical complication rates or relationships between comorbidity burden and survival were observed. There were no significant changes in demographic variables, except for admission rate, gender (p = 0.013), and place of accident (p = 0.049). Conclusion: Surgeons should be reassured to take COVID-19 precautions, as this study did not show higher perioperative mortality due to COVID-19 measures. Under the current circumstances, with possibly reduced surgical and hospital bed capacities, it is expected that hip fractures may continue to require a high degree of resources
C9orf72 repeat length might influence clinical sub-phenotypes in dementia patients
Background: C9orf72 repeat expansions have been observed in a wide variety of neurodegenerative disorders. The cut-off between normal and pathogenic alleles is not well established as repeat sizing methods are often semi-quantitative. However, intermediate alleles might influence disease prevalence and phenotype, as seen for other repeat expansion disorders. We aimed to further delineate the prevalence of small, intermediate and expanded C9orf72 alleles and elucidate their potential influence on the disease phenotype. Methods: DNA derived from patients (n = 1804) and healthy individuals (n = 643) was obtained from multiple collectives in Austria. Genotyping was performed using a two-step PCR assay followed by Southern blotting. Results: 3.4% of clinically diagnosed frontotemporal dementia (FTD; n = 5/147) cases and 0.8% of clinically diagnosed Alzheimer's disease (AD; n = 5/602) cases were carriers of a pathological C9orf72 repeat expansion. A significantly earlier disease onset was detected in expansion carriers compared to non-carriers in the FTD and AD cohorts (median 50 years, range 39–64 vs. median 64 years, range 36–92, p = 0.018 and median 63 years, range 54–71 vs. median 74 years, range 45–92, p = 0.006, respectively). C9orf72 intermediate alleles were significantly associated with cerebellar symptoms (p = 0.0004) and sensory deficits in the dementia cohort (p = 0.01). Conclusions: C9orf72 repeat expansion carriers showed earlier disease onset compared to non-carriers with clinical diagnosis of FTD and AD. Furthermore, C9orf72 intermediate repeats might modify the phenotypic expression in dementia