Epidemiology of ATTRV30M neuropathy in Cyprus and the modifier effect of complement C1q on the age of disease onset

Andreou, Savanna; Panayiotou, Elena; Michailidou, Kyriaki; Pirpa, Panayiota; Hadjisavvas, Andreas; Salloukh, Adonis El; Barnes, Daniel R.; Antoniou, Antonis C.; Agathangelou, Petros; Papastavrou, Katia; Christodoulou, Kyproula; Tanteles, George A.; Kyriakides, Theodoros

doi:10.1080/13506129.2018.1534731

Cited by 15 publications

(16 citation statements)

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“…In ATTRV30M, diversity in the age of onset among different populations is a recognized phenomenon [5,26]. Anticipation (younger onset in the offspring, usually with increased severity) has also been repeatedly reported in ATTRV30M but is not common in ATTRA97S [18,[27][28][29][30][31]. Similar to patients from Malaysia [21], the paternal or maternal ancestors of our patients migrated from southern China in the 19th century.…”

Section: Discussionsupporting

confidence: 65%

Ala97Ser transthyretin amyloidosis-associated polyneuropathy, clinical and neurophysiological profiles in a Thai cohort

et al. 2021

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Background Ala97Ser transthyretin amyloidosis-associated polyneuropathy (ATTRA97S-PN) is a rare form of inherited polyneuropathy, usually manifesting with late-onset (> 50) progressive polyneuropathy. This mutation is mostly prevalent in Taiwanese and Han-Chinese individuals. The aim of this study was to describe the clinical and comprehensive neurophysiological profiles of ATTRA97S-PN in Thai patients. Methods The clinical profiles and serial neurophysiologic studies (nerve conduction study (NCS), quantitative sensory test (QST), and comprehensive autonomic function test (AFT)) of symptomatic ATTRA97S-PN patients who had been followed-up at King Chulalongkorn Memorial Hospital during 2010–2020 were retrospectively reviewed. Results Nine symptomatic patients (55.6 % were male) from four unrelated families were included. All were Thais of mixed Thai Chinese descent. The mean age of onset was 48.3 (32–60) years. The mean age at diagnosis was 54.8 (33–66) years. Three patients developed early-onset (< 40y) polyneuropathy. The mean Neuropathy Impairment Score was 41.33 (10–92) at diagnosis. Sensory (9/9) and autonomic (9/9) neuropathies were more frequent than motor neuropathy (5/9), which appeared in the late stage of disease. Hypoesthesia in the feet, and gastrointestinal autonomic symptoms were frequently reported as the initial symptoms. The course of neuropathy progressed over years to decades. The worsening of neuropathy tended to progress faster once motor nerves were affected in both clinical and neurophysiological aspects. Concurrent cardiac amyloidosis was found in 6/9 patients. NCS showed length-dependent sensorimotor axonal polyneuropathy in 5/9 patients, and median neuropathy at the wrist (mostly bilateral) in 7/9 patients. QST showed abnormalities in the vibratory detection threshold, the cold detection threshold and the heat pain sensation in 8/9, 8/9 and 7/7 tested patients, respectively. AFT results were abnormal in all. The mean composite autonomic severity score was 5 (3–9). Conclusions This clinical study is the first of ATTRA97S-PN in Thai patients. The mixed polyneuropathy-cardiopathy phenotype was the most common manifestation. In this cohort, the age of onset was lower, and the course of neuropathy was relatively longer, than that in previous studies. Some patients may develop early-onset polyneuropathy. This mutation has not yet been documented in any population other than Han Chinese-related populations, probably suggesting a founder effect. Further studies are warranted.

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Section: Discussionsupporting

confidence: 65%

Ala97Ser transthyretin amyloidosis-associated polyneuropathy, clinical and neurophysiological profiles in a Thai cohort

et al. 2021

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“…DNA was extracted from peripheral blood lymphocytes as described elsewhere (14). SNP genotyping was performed using Taqman genotype assays (Thermo Fisher Scientific).…”

Section: Methodsmentioning

confidence: 99%

Genetic and Environmental Factors Contributing to Parkinson's Disease: A Case-Control Study in the Cypriot Population

et al. 2019

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Introduction: Parkinson's disease (PD) is a neurodegenerative disorder affecting a substantial proportion of the elderly Cypriot population. The objective of this study was to evaluate PD risk variants that have been identified previously in Genome Wide Association Studies (GWAS) and to find environmental factors that are predictors for PD onset in the Cypriot population.Methods: A case-control study was conducted with a total of 235 PD patients and 464 healthy controls of Greek-Cypriot ethnicity. Demographic and lifestyle characteristics, exposure to PD risk factors and clinical data were collected. Moreover, 13 previously GWAS-identified PD risk variants were genotyped. Univariate and multivariate regression analyses examined the association between a number of environmental and genetic factors and PD.Results: Multivariable regression analysis revealed that exposure to both pesticides and other toxic substances (P = 0.03), severe head injury accompanied with fainting (P = 0.001), nuts consumption (P = 0.004), red meat consumption (P = 0.02), and soft drinks consumption (P = 0.008) were increasing the risk for PD, whereas cumulative smoking (P = 0.02), and fish consumption (P = 0.02) were decreasing the risk for PD. Five out of the 13 tested SNPs (rs12185268, rs6599389, rs356220, rs13312, and rs17649553) were confirmed to be nominally significantly associated (P < 0.05) with PD risk in the Cypriot population.Conclusions: Collectively, this case-control study has shed some light on the nature of PD epidemiology in Cyprus, by demonstrating a number of genetic and environmental determinants of PD in the Cypriot population.

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“…While the reasons for the different age of onset in patients with ATTRv Val30Met amyloidosis are still not fully elucidated, reports have identified several different genetic factors that may influence age of disease onset, including sex [ 29 ], C1Q polymorphisms [ 30 , 31 ], single nucleotide haplotype polymorphisms in the TTR gene [ 32 , 33 ], mitochondrial haplogroup polymorphisms [ 34 ], RBP4 and AR gene variation [ 35 ], and mitochondrial DNA copy number [ 36 ]. It may be that environmental factors are also involved.…”

Section: Discussionmentioning

confidence: 99%

Characteristics of Patients with Late- vs. Early-Onset Val30Met Transthyretin Amyloidosis from the Transthyretin Amyloidosis Outcomes Survey (THAOS)

et al. 2021

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Introduction: Hereditary transthyretin amyloidosis (ATTRv amyloidosis) is a clinically heterogeneous disease caused by mutations in the transthyretin (TTR) gene. The most common mutation, Val30Met, can manifest as an early-or late-onset disease. Methods: The Transthyretin Amyloidosis Outcomes Survey (THAOS) is an ongoing, global, longitudinal, observational survey of patients with transthyretin amyloidosis, including both inherited and wild-type disease and asymptomatic patients with TTR mutations. This is a descriptive analysis of symptomatic patients with ATTRv Val30Met amyloidosis with late-(age at least 50 years) vs. early-onset (age less than 50 years) disease in THAOS (data cutoff August 1, 2019). Results: Of 1389 patients with ATTRv Val30-Met amyloidosis, 491 (35.3%) had late-onset disease. Compared with early-onset, patients with late-onset were more likely to be male (66.2% vs. 53.6%) and have a longer mean (standard deviation [SD]) time from onset to diagnosis (3.8 [3.4] vs. 2.7 [4.1] years). Lateonset disease was associated with more severe neurological impairment at enrollment (median [10th, 90th percentile] derived Neuropathy Impairment Score in the Lower Limbs, 25.0 [4.0, 69.3] vs. 8.0 [0, 54.8]; Neurologic Composite Score, 42.0 [2.0, 155.0] vs. 21.0 [0, 102.0]). Cardiac findings were more prominent in lateonset disease. An overall interpretation of electrocardiogram as abnormal was reported in 72.1% of late-onset patients (vs. 44.3% earlyonset). A left-ventricular septal thickness of at least 12 mm was reported in 69.7% of late-onset patients (vs. 14.6% early-onset). All differences were statistically significant (p \ 0.001). Conclusion: In THAOS, late-onset ATTRv Val30Met amyloidosis is common, presenting with more severe neurologic and cardiac findings at enrollment. Heterogeneity of disease may make it more difficult to diagnose. Increased recognition of late-onset ATTRv Val30Met amyloidosis could lead to moreThe members of the THAOS investigators group was processed under acknowledgements section.

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Epidemiology of ATTRV30M neuropathy in Cyprus and the modifier effect of complement C1q on the age of disease onset

Cited by 15 publications

References 37 publications

Ala97Ser transthyretin amyloidosis-associated polyneuropathy, clinical and neurophysiological profiles in a Thai cohort

Ala97Ser transthyretin amyloidosis-associated polyneuropathy, clinical and neurophysiological profiles in a Thai cohort

Genetic and Environmental Factors Contributing to Parkinson's Disease: A Case-Control Study in the Cypriot Population

Characteristics of Patients with Late- vs. Early-Onset Val30Met Transthyretin Amyloidosis from the Transthyretin Amyloidosis Outcomes Survey (THAOS)

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