| 1. |
- Adams, David, et al.
(författare)
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First European consensus for diagnosis, management, and treatment of transthyretin familial amyloid polyneuropathy
- 2016
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Ingår i: Current Opinion in Neurology. - : Lippincott Williams & Wilkins. - 1350-7540 .- 1473-6551. ; 29, s. S14-S26
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Tidskriftsartikel (refereegranskat)abstract
- Purpose of review Early and accurate diagnosis of transthyretin familial amyloid polyneuropathy (TTR-FAP) represents one of the major challenges faced by physicians when caring for patients with idiopathic progressive neuropathy. There is little consensus in diagnostic and management approaches across Europe. Recent findings The low prevalence of TTR-FAP across Europe and the high variation in both genotype and phenotypic expression of the disease means that recognizing symptoms can be difficult outside of a specialized diagnostic environment. The resulting delay in diagnosis and the possibility of misdiagnosis can misguide clinical decision-making and negatively impact subsequent treatment approaches and outcomes. Summary This review summarizes the findings from two meetings of the European Network for TTR-FAP (ATTReuNET). This is an emerging group comprising representatives from 10 European countries with expertise in the diagnosis and management of TTR-FAP, including nine National Reference Centres. The current review presents management strategies and a consensus on the gold standard for diagnosis of TTR-FAP as well as a structured approach to ongoing multidisciplinary care for the patient. Greater communication, not just between members of an individual patient's treatment team, but also between regional and national centres of expertise, is the key to the effective management of TTR-FAP.
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| 2. |
- Berk, John L., et al.
(författare)
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Repurposing Diflunisal for Familial Amyloid Polyneuropathy : A Randomized Clinical Trial
- 2013
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Ingår i: Journal of the American Medical Association (JAMA). - : American Medical Association (AMA). - 0098-7484 .- 1538-3598. ; 310:24, s. 2658-2667
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Tidskriftsartikel (refereegranskat)abstract
- IMPORTANCE Familial amyloid polyneuropathy, a lethal genetic disease caused by aggregation of variant transthyretin, induces progressive peripheral nerve deficits and disability. Diflunisal, a nonsteroidal anti-inflammatory agent, stabilizes transthyretin tetramers and prevents amyloid fibril formation in vitro. OBJECTIVE To determine the effect of diflunisal on polyneuropathy progression in patients with familial amyloid polyneuropathy. DESIGN, SETTING, AND PARTICIPANTS International randomized, double-blind, placebo-controlled study conducted among 130 patients with familial amyloid polyneuropathy exhibiting clinically detectable peripheral or autonomic neuropathy at amyloid centers in Sweden (Umea), Italy (Pavia), Japan (Matsumoto and Kumamoto), England (London), and the United States (Boston, Massachusetts; New York, New York; and Rochester, Minnesota) from 2006 through 2012. INTERVENTION Participants were randomly assigned to receive diflunisal, 250 mg (n=64), or placebo (n=66) twice daily for 2 years. MAIN OUTCOMES AND MEASURES The primary end point, the difference in polyneuropathy progression between treatments, was measured by the Neuropathy Impairment Score plus 7 nerve tests (NIS+7) which ranges from 0 (no neurological deficits) to 270 points (no detectable peripheral nerve function). Secondary outcomes included a quality-of-life questionnaire (36-Item Short-Form Health Survey [SF-36]) and modified body mass index. Because of attrition, we used likelihood-based modeling and multiple imputation analysis of baseline to 2-year data. RESULTS By multiple imputation, the NIS+7 score increased by 25.0 (95% CI, 18.4-31.6) points in the placebo group and by 8.7 (95% CI, 3.3-14.1) points in the diflunisal group, a difference of 16.3 points (95% CI, 8.1-24.5 points; P < .001). Mean SF-36 physical scores decreased by 4.9 (95% CI, -7.6 to -2.2) points in the placebo group and increased by 1.5 (95% CI, -0.8 to 3.7) points in the diflunisal group (P < .001). Mean SF-36 mental scores declined by 1.1 (95% CI, -4.3 to 2.0) points in the placebo group while increasing by 3.7 (95% CI, 1.0-6.4) points in the diflunisal group (P = .02). By responder analysis, 29.7% of the diflunisal group and 9.4% of the placebo group exhibited neurological stability at 2 years (<2-point increase in NIS+7 score; P = .007). CONCLUSIONS AND RELEVANCE Among patients with familial amyloid polyneuropathy, the use of diflunisal compared with placebo for 2 years reduced the rate of progression of neurological impairment and preserved quality of life. Although longer-term follow-up studies are needed, these findings suggest benefit of this treatment for familial amyloid polyneuropathy.
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| 3. |
- Berk, John L, et al.
(författare)
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The diflunisal trial : study accrual and drug tolerance
- 2012
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Ingår i: Amyloid. - : Informa UK Limited. - 1350-6129 .- 1744-2818. ; 19:S1, s. 37-38
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Tidskriftsartikel (refereegranskat)abstract
- Familial amyloidotic polyneuropathy (FAP) is a protein folding disorder that induces neuropathy and cardiomyopathy, leading to death within 7-15 years after onset of clinical disease. In vitro, small ligands binding the thyroid hormone docking site stabilize tetrameric transthyretin, inhibiting amyloid fibril formation. We undertook a randomized, placebo-controlled clinical trial to determine whether diflunisal, a well-known non-steroidal anti-inflammatory drug (NSAID) alters neurologic disease progression in FAP. We enrolled 130 subjects with wide age and FAP mutation representation. To date, few recognized complications of NSAIDs have occurred in the study cohort. Data collection will be completed by November 2012.
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| 4. |
- Coelho, Teresa, et al.
(författare)
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Characteristics of Patients with Hereditary Transthyretin Amyloidosis-Polyneuropathy (ATTRv-PN) in NEURO-TTRansform, an Open-label Phase 3 Study of Eplontersen
- 2023
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Ingår i: Neurology and Therapy. - : Springer Nature. - 2193-8253 .- 2193-6536. ; 12, s. 267-287
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Hereditary transthyretin (ATTRv) amyloidosis is a rare, severe, progressive, debilitating, and ultimately fatal disease caused by systemic deposition of transthyretin (TTR) amyloid fibrils. ATTRv amyloidosis occurs in both males and females. Eplontersen (ION-682884), a ligand-conjugated antisense oligonucleotide designed to degrade hepatic TTR mRNA, is being evaluated for the treatment of ATTRv amyloidosis with polyneuropathy (ATTRv-PN) in the phase 3, international, multicenter, open-label NEURO-TTRansform study (NCT04136184). To describe the study population of this pivotal trial, here we report the baseline characteristics of patients enrolled in the NEURO-TTRansform study.Methods: Patients eligible for NEURO-TTRansform were 18–82 years old with a diagnosis of ATTRv-PN and Coutinho stage 1 (ambulatory without assistance) or stage 2 (ambulatory with assistance) disease; documented TTR gene variant; signs and symptoms consistent with neuropathy associated with ATTRv; no prior liver transplant; and New York Heart Association (NYHA) functional class I or II.Results: The NEURO-TTRansform study enrolled 168 patients across 15 countries/territories (North America, 15.5%; Europe, 38.1%; South America/Australia/Asia, 46.4%). At baseline, the study cohort had a mean age of 52.8 years, 69.0% of patients were male, and 78.0% of patients were White. The V30M variant was most prevalent (60.1% of patients), and prevalence varied by region. Overall, 56.5% and 17.3% of patients had received previous treatment with tafamidis or diflunisal, respectively. A majority of patients (79.2%) had Coutinho stage 1 disease (unimpaired ambulation) and early (before age 50) disease onset (53.0%). Time from diagnosis to enrollment was 46.6 (57.4) months (mean [standard deviation]). Most patients had a baseline polyneuropathy disability (PND) score of I (40.5%) or II (41.1%), and the mean modified Neuropathy Impairment Score + 7 (mNIS + 7) was 79.0.Conclusion: The recruited population in the ongoing NEURO-TTRansform study has global representation characteristic of contemporary clinical practice.
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| 5. |
- Coelho, Teresa, et al.
(författare)
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Eplontersen for Hereditary Transthyretin Amyloidosis with Polyneuropathy
- 2023
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Ingår i: Journal of the American Medical Association (JAMA). - : American Medical Association (AMA). - 0098-7484 .- 1538-3598. ; 330:15, s. 1448-1458
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Tidskriftsartikel (refereegranskat)abstract
- Importance: Transthyretin gene silencing is an emerging treatment strategy for hereditary transthyretin (ATTRv) amyloidosis.Objective: To evaluate eplontersen, an investigational ligand-conjugated antisense oligonucleotide, in ATTRv polyneuropathy.Design, Setting, and Participants: NEURO-TTRansform was an open-label, single-group, phase 3 trial conducted at 40 sites across 15 countries (December 2019-April 2023) in 168 adults with Coutinho stage 1 or 2 ATTRv polyneuropathy, Neuropathy Impairment Score 10-130, and a documented TTR variant. Patients treated with placebo from NEURO-TTR (NCT01737398; March 2013-November 2017), an inotersen trial with similar eligibility criteria and end points, served as a historical placebo ("placebo") group.Interventions: Subcutaneous eplontersen (45 mg every 4 weeks; n = 144); a small reference group received subcutaneous inotersen (300 mg weekly; n = 24); subcutaneous placebo weekly (in NEURO-TTR; n = 60).Main Outcomes and Measures: Primary efficacy end points at week 65/66 were changes from baseline in serum transthyretin concentration, modified Neuropathy Impairment Score +7 (mNIS+7) composite score (scoring range, -22.3 to 346.3; higher scores indicate poorer function), and Norfolk Quality of Life Questionnaire-Diabetic Neuropathy (Norfolk QoL-DN) total score (scoring range, -4 to 136; higher scores indicate poorer quality of life). Analyses of efficacy end points were based on a mixed-effects model with repeated measures adjusted by propensity score weights.Results: Among 144 eplontersen-treated patients (mean age, 53.0 years; 69% male), 136 (94.4%) completed week-66 follow-up; among 60 placebo patients (mean age, 59.5 years; 68% male), 52 (86.7%) completed week-66 follow-up. At week 65, adjusted mean percentage reduction in serum transthyretin was -81.7% with eplontersen and -11.2% with placebo (difference, -70.4% [95% CI, -75.2% to -65.7%]; P <.001). Adjusted mean change from baseline to week 66 was lower (better) with eplontersen vs placebo for mNIS+7 composite score (0.3 vs 25.1; difference, -24.8 [95% CI, -31.0 to -18.6; P <.001) and for Norfolk QoL-DN (-5.5 vs 14.2; difference, -19.7 [95% CI, -25.6 to -13.8]; P <.001). Adverse events by week 66 that led to study drug discontinuation occurred in 6 patients (4%) in the eplontersen group vs 2 (3%) in the placebo group. Through week 66, there were 2 deaths in the eplontersen group consistent with known disease-related sequelae (cardiac arrhythmia; intracerebral hemorrhage); there were no deaths in the placebo group.Conclusions and Relevance: In patients with ATTRv polyneuropathy, the eplontersen treatment group demonstrated changes consistent with significantly lowered serum transthyretin concentration, less neuropathy impairment, and better quality of life compared with a historical placebo.Trial Registration: ClinicalTrials.gov Identifier: NCT04136184; EU Clinical Trials Register: EudraCT 2019-001698-10.
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| 6. |
- Ihse, Elisabet, et al.
(författare)
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Amyloid fibrils containing fragmented ATTR may be the standard fibril composition in ATTR amyloidosis
- 2013
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Ingår i: Amyloid. - : Informa UK Limited. - 1350-6129 .- 1744-2818. ; 20:3, s. 142-150
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Tidskriftsartikel (refereegranskat)abstract
- The clinical phenotype of familial ATTR amyloidosis depends to some extent on the particular mutation, but differences exist also within mutations. We have previously described that two types of amyloid fibril compositions exist among Swedish ATTRV30M amyloidosis patients, one consisting of a mixture of intact and fragmented ATTR (type A) and one consisting of mainly intact ATTR (type B). The fibril types are correlated to phenotypic differences. Patients with ATTR fragments have a late onset and develop cardiomyopathy, while patients without fragments have an early onset and less myocardial involvement. The present study aimed to determine whether this correlation between fibril type and phenotype is valid for familial ATTR amyloidosis in general. Cardiac or adipose tissues from 63 patients carrying 29 different TTR non-V30M mutations as well as 13 Japanese ATTRV30M patients were examined. Fibril type was determined by western blotting and compared to the patients' age of onset and degree of cardiomyopathy. All ATTR non-V30M patients had a fibril composition with ATTR fragments, except two ATTRY114C patients. No clear conclusions could be drawn about a phenotype to fibril type correlation among ATTR non-V30M patients. In contrast, Japanese ATTRV30M patients showed a similar correlation as previously described for Swedish ATTRV30M patients. This study shows that a fibril composition with fragmented ATTR is very common in ATTR amyloidosis, and suggests that fibrils composed of only full-length ATTR is an exception found only in a subset of patients.
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| 7. |
- Ihse, Elisabet, 1977-, et al.
(författare)
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Amyloid fibrils with fragmented ATTR may be the rule in non-Val30Met ATTR amyloidosis
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- The clinical phenotype of familial ATTR amyloidosis depends to some extent on the particular mutation, but differences exist also within mutations. We have previously described that two types of amyloid fibril compositions exist among Swedish ATTRV30M amyloidosis patients, one consisting of a mixture of intact and fragmented ATTR (type A) and one composed of only intact ATTR (type B). Patients with type A fibrils have a late age of onset and signs of cardiomyopathy, while patients with type B fibrils have an early onset and much less myocardial involvement. The present study aimed to determine if the correlation between fibril type and clinical phenotype is true for familial amyloidosis in general. Cardiac and/or adipose tissue from 48 patients carrying 21 different non-TTRV30M mutations were examined, as well as 7 non-Swedish ATTRV30M patients. Fibril type was determined with western blotting and compared to the patients´ age of onset and degree of cardiomyopathy. Non-Swedish V30M patients showed the same correlation as described for Swedish V30M patients, with fibrils of only full-length ATTR (type B) linked to less myocardial involvement. In contrast, all patients with non-V30M mutations had a fibril composition with ATTR fragments (type A). Some of these patients had onset of disease at young age. The vast majority had increased thickness of left cardiac ventricle, but a few individuals had values within normal limits. This study shows that a fibril composition with fragmented ATTR is very common in ATTR amyloidosis. It also suggests that fibrils composed of only full-length ATTR is an exception, perhaps only found among young ATTRV30M amyloidosis patients.
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| 8. |
- Israni, Muskan, et al.
(författare)
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Current Transition Practice for Primary Immunodeficiencies and Autoinflammatory Diseases in Europe: a RITA-ERN Survey.
- 2023
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Ingår i: Journal of clinical immunology. - : Springer Science and Business Media LLC. - 0271-9142 .- 1573-2592. ; 43:1, s. 206-216
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Tidskriftsartikel (refereegranskat)abstract
- Due to the absence of curative treatments for inborn errors of immunity (IEI), children born with IEI require long-term follow-up for disease manifestations and related complications that occur over the lifespan. Effective transition from pediatric to adult services is known to significantly improve adherence to treatment and long-term outcomes. It is currently not known what transition services are available for young people with IEI in Europe.To understand the prevalence and practice of transition services in Europe for young people with IEI, encompassing both primary immunodeficiencies (PID) and systemic autoinflammatory disorders (AID).A survey was generated by the European Reference Network on immunodeficiency, autoinflammatory, and autoimmune diseases Transition Working Group and electronically circulated, through professional networks, to pediatric centers across Europe looking after children with IEI.Seventy-six responses were received from 52 centers, in 45 cities across 17 different countries. All services transitioned patients to adult services, mainly to specialist PID or AID centers, typically transferring up to ten patients to adult care each year. The transition process started at a median age of 16-18years with transfer to the adult center occurring at a median age of 18-20years. 75% of PID and 68% of AID centers held at least one joint appointment with pediatric and adult services prior to the transfer of care. Approximately 75% of PID and AID services reported having a defined transition process, but few centers reported national disease-specific transition guidelines to refer to.Transition services for children with IEI in Europe are available in many countries but lack standardized guidelines to promote best practice.
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| 9. |
- Nilsson, Oktawia, et al.
(författare)
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Structure dynamics of ApoA-I amyloidogenic variants in small HDL increase their ability to mediate cholesterol efflux
- 2021
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Ingår i: Journal of Lipid Research. - 0022-2275. ; 62
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Tidskriftsartikel (refereegranskat)abstract
- Apolipoprotein A-I (ApoA-I) of high density lipoproteins (HDLs) is essential for the transportation of cholesterol between peripheral tissues and the liver. However, specific mutations in ApoA-I of HDLs are responsible for a late-onset systemic amyloidosis, the pathological accumulation of protein fibrils in tissues and organs. Carriers of these mutations do not exhibit increased cardiovascular disease risk despite displaying reduced levels of ApoA-I/ HDL cholesterol. To explain this paradox, we show that the HDL particle profiles of patients carrying either L75P or L174S ApoA-I amyloidogenic variants show a higher relative abundance of the 8.4-nm versus 9.6-nm particles and that serum from patients, as well as reconstituted 8.4- and 9.6-nm HDL particles (rHDL), possess increased capacity to catalyze cholesterol efflux from macrophages. Synchrotron radiation circular dichroism and hydrogendeuterium exchange revealed that the variants in 8.4-nm rHDL have altered secondary structure composition and display a more flexible binding to lipids than their native counterpart. The reduced HDL cholesterol levels of patients carrying ApoA-I amyloidogenic variants are thus balanced by higher proportion of small, dense HDL particles, and better cholesterol efflux due to altered, region-specific protein structure dynamics.
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| 10. |
- Nilsson, Oktawia, et al.
(författare)
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Structure dynamics of ApoA-I amyloidogenic variants in small HDL increase their ability to mediate cholesterol efflux
- 2021
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Ingår i: Journal of Lipid Research. - : Elsevier. - 0022-2275 .- 1539-7262. ; 62
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Tidskriftsartikel (refereegranskat)abstract
- Apolipoprotein A-I (ApoA-I) of high density lipoproteins (HDLs) is essential for the transportation of cholesterol between peripheral tissues and the liver. However, specific mutations in ApoA-I of HDLs are responsible for a late-onset systemic amyloidosis, the pathological accumulation of protein fibrils in tissues and organs. Carriers of these mutations do not exhibit increased cardiovascular disease risk despite displaying reduced levels of ApoA-I/HDL cholesterol. To explain this paradox, we show that the HDL particle profiles of patients carrying either L75P or L174S ApoA-I amyloidogenic variants show a higher relative abundance of the 8.4-nm versus 9.6-nm particles and that serum from patients, as well as reconstituted 8.4- and 9.6-nm HDL particles (rHDL), possess increased capacity to catalyze cholesterol efflux from macrophages. Synchrotron radiation circular dichroism and hydrogen-deuterium exchange revealed that the variants in 8.4-nm rHDL have altered secondary structure composition and display a more flexible binding to lipids than their native counterpart. The reduced HDL cholesterol levels of patients carrying ApoA-I amyloidogenic variants are thus balanced by higher proportion of small, dense HDL particles, and better cholesterol efflux due to altered, region-specific protein structure dynamics.
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| 11. |
- Obici, Laura, et al.
(författare)
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Diagnosis and treatment of gastrointestinal dysfunction in hereditary TTR amyloidosis
- 2019
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Ingår i: Clinical Autonomic Research. - : Springer. - 0959-9851 .- 1619-1560. ; 29, s. 55-63
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Forskningsöversikt (refereegranskat)abstract
- Purpose: To review the management of gastrointestinal symptoms in patients with hereditary transthyretin amyloidosis, discussing diagnostic evaluations, assessment of disease progression and therapeutic strategies that could be implemented in routine practice.Methods: Literature review. Key search terms included "gastrointestinal symptoms", "autonomic neuropathy", "hereditary transthyretin amyloidosis" and "familial amyloid polyneuropathy".Results: Gastrointestinal disturbances are a common and serious manifestation of hereditary transthyretin amyloidosis, with significant effects on patients' quality of life and demonstrating a strong association with mortality. Gastrointestinal involvement is more often subclinical in the early stages of the disease, although in some patients gastric and/or bowel abnormalities may be the inaugural symptoms. In both cases, under-recognition, delayed investigation and suboptimal treatment frequently occur. A clear understanding of the mechanisms underlying gastrointestinal dysfunction in hereditary transthyretin amyloidosis is still lacking, but similar to diabetic enteropathy, multiple pathophysiological alterations seem to play a role.Conclusions: Early detection and treatment of gastrointestinal disturbances is key to the successful treatment of this devastating disease. Gastroenterologists play a valuable role in both the diagnosis and the timely management of gastrointestinal symptoms in hereditary transthyretin amyloidosis and should, therefore, be part of a multidisciplinary and comprehensive approach to this disorder.
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| 12. |
- Obici, Laura, et al.
(författare)
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Recommendations for presymptomatic genetic testing and management of individuals at risk for hereditary transthyretin amyloidosis
- 2016
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Ingår i: Current Opinion in Neurology. - 1350-7540 .- 1473-6551. ; 29, s. S27-S35
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Tidskriftsartikel (refereegranskat)abstract
- Purpose of review These recommendations highlight recent experience in genetic counselling for the severe autosomal-dominant, late-onset transthyretin familial amyloid polyneuropathy (TTR-FAP) disease, and present a structured approach towards identification and monitoring of asymptomatic carriers of the mutated gene. Recent findings The effectiveness of current treatment options is still limited in patients with TTR-FAP beyond stage I. Diagnosis in the early stages of TTR-FAP is essential to prevent or delay the progression of disease. Existing legal and cultural issues differ among countries within Europe. Experts of the European Network for TTRFAP (ATTReuNET) concluded that genetic counselling for diagnosed individuals and at-risk family members is mostly beneficial and should be carried out with care by trained professionals. Systematic and regular monitoring of an asymptomatic carrier is necessary to detect early signs of TTR-FAP and maximize the effectiveness of treatment. This includes five areas of assessment: history/clinical examination, sensorimotor function, autonomic dysfunction, cardiac function, and renal function. At least two related symptoms and positive biopsy findings are required to confirm diagnosis of TTR-FAP. Summary Early detection of TTR-FAP is essential to improve the prognosis of TTR-FAP. ATTReuNET recommends genetic counselling and routine monitoring for asymptomatic carriers of TTR-FAP.
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| 13. |
- Parman, Yesim, et al.
(författare)
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Sixty years of transthyretin familial amyloid polyneuropathy (TTR-FAP) in Europe : where are we now? A European network approach to defining the epidemiology and management patterns for TTR-FAP
- 2016
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Ingår i: Current Opinion in Neurology. - 1350-7540 .- 1473-6551. ; 29, s. S3-S13
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Tidskriftsartikel (refereegranskat)abstract
- Purpose of review Transthyretin familial amyloid polyneuropathy (TTR-FAP) is a highly disabling, life-threatening disease characterized by progressive sensorimotor and autonomic neuropathy. The profile of the disease across Europe is inadequately understood at present. Recent findings The incidence and clinical presentation of TTR-FAP varies widely within Europe, with early and late-onset disease subtypes. In those regions in which the disease is endemic (Portugal, Sweden, Cyprus, and Majorca), a Val30Met substitution in the TTR gene is the predominant genetic cause, whereas in the rest of Europe, cases of TTR-FAP are mainly sporadic with genetic heterogeneity. Current management strategies lack cohesion and patients can experience years of misdiagnosis and suboptimal treatment. Summary The article aims to disseminate the findings and recommendations from two recent meetings of the European Network for TTR-FAP (ATTReuNET), a panel comprising representatives from 10 European countries (Bulgaria, Cyprus, France, Germany, Italy, the Netherlands, Portugal, Spain, Sweden, and Turkey) with expertise in the diagnosis and management of TTR-FAP. We explore the epidemiology and genetic mark of TTR-FAP across Europe and assess current management strategies, with a view to developing an alternative framework - a networked approach to disease management with an emphasis on collaboration and sharing of best practice.
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| 14. |
- Rowczenio, Dorota M., et al.
(författare)
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Online Registry for Mutations in Hereditary Amyloidosis Including Nomenclature Recommendations
- 2014
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Ingår i: Human Mutation. - : Hindawi Limited. - 1059-7794 .- 1098-1004. ; 35:9, s. E2403-E2412
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Tidskriftsartikel (refereegranskat)abstract
- Hereditary systemic amyloidosis comprises a group of rare monogenic diseases inherited in an autosomal dominant fashion. It is associated with mutations in genes encoding eight different proteins, including transthyretin, apolipoprotein AI, apolipoprotein AII, lysozyme, fibrinogen A alpha-chain, cystatin C, gelsolin and beta-2-microglobulin. With support from the EU FP6 EURAMY project we have designed an online registry of genes and mutations in hereditary amyloidosis including their associated clinical phenotypes, with a view to having a single free online portal for the collection and distribution of this information. Users can search the registry by either mutation, phenotype or authors who have published or submitted mutations. It provides a submission form for reporting newly identified mutations. We also wanted to introduce nomenclature which complies with recommendations set out by Human Genome Variation Society and HUGO Gene Nomenclature Committee for description of new and known genetic variants. We hope this registry would be a useful and convenient tool for the medical and scientific community.
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