Awareness and motives for use and non-use of preimplantation genetic diagnosis in familial amyloid polyneuropathy mutation carriers

2014 ◽  
Vol 34 (9) ◽  
pp. 886-892 ◽  
Author(s):  
Kátia Valdrez ◽  
Susana Silva ◽  
Teresa Coelho ◽  
Elisabete Alves
Keyword(s):  
Preimplantation Genetic Diagnosis ◽  
Genetic Diagnosis ◽  
Familial Amyloid Polyneuropathy ◽  
Mutation Carriers ◽  
Amyloid Polyneuropathy

scholarly journals Prevalência do Uso de Diagnóstico Genético Pré-Implantação na Unidade Clínica de Paramiloidose do Centro Hospitalar do Porto

2014 ◽  
Vol 27 (6) ◽  
pp. 710 ◽  
Author(s):  
Kátia Valdrez ◽  
Elisabete Alves ◽  
Teresa Coelho ◽  
Susana Silva
Keyword(s):  
Preimplantation Genetic Diagnosis ◽  
Household Income ◽  
Assisted Reproductive Technologies ◽  
Genetic Diagnosis ◽  
Reproductive Technologies ◽  
Familial Amyloid Polyneuropathy ◽  
Chi Square ◽  
National Board ◽  
Amyloid Polyneuropathy ◽  
Serious Disease

<strong>Introduction:</strong> The Familial Amyloid Polyneuropathy, with the world’s largest focus in Portugal, is recognized by the National Board of Assisted Reproductive Technologies as a serious disease eligible for Preimplantation Genetic Diagnosis. This study aims to determine the prevalence of the use of Preimplantation Genetic Diagnosis in FAP carriers followed in Unidade Clínica de Paramiloidose, Centro Hospitalar do Porto, and to identify the associated factors.<br /><strong>Material and Methods:</strong> Between January and May 2013, a representative sample of Portuguese Familial Amyloid Polyneuropathy carriers, aged between 18 and 55 years, was systematically recruited. The analysis is based on 111 carriers with previous familial diagnosis, who reported having ever tried to get pregnant after 2001. Data on sociodemographic characteristics and use of Preimplantation Genetic Diagnosis were collected through a self-administered questionnaire. Proportions were compared using the chi-square test. Crude and adjusted odds ratios (OR) and the respective confidence intervals of 95% (95% CI) were estimated using multivariate<br />logistic regression.<br /><strong>Results:</strong> The prevalence of use of Preimplantation Genetic Diagnosis was 20.7% (95% CI: 13.6-29.5). After adjustment, a household income above 1000 €/month (OR = 11.87; 95% CI 2.87-49.15) was directly associated with the use of Preimplantation Genetic Diagnosis, while carriers with an individual diagnosis (OR = 0.15; 95% CI 0.04-0.57) and children born after 2001 (OR = 0.07; 95% CI 0.02-0.32) revealed a prevalence of use significantly lower than those with a individual diagnosis and children born before 2001.<br /><strong>Discussion:</strong> The low prevalence of use of Preimplantation Genetic Diagnosis, as well as the less frequent use of the technique by those with a lower household income, shows the importance of improving access to Preimplantation Genetic Diagnosis in the case of Familial Amyloid Polyneuropathy.<br /><strong>Conclusion:</strong> This work contributes to increase the sensitivity of health professionals around the use and accessibility to Preimplantation Genetic Diagnosis among Familial Amyloid Polyneuropathy carriers.<br /><strong>Keywords:</strong> Preimplantation Diagnosis; Amyloid Neuropathies, Familial; Genetic Testing; Assisted Reproductive Technologies.

scholarly journals Clinicopathological correlations of sural nerve biopsies in TTR Val30Met familial amyloid polyneuropathy

2019 ◽  
Vol 1 (1) ◽  
Author(s):  
Armindo Fernandes ◽  
Teresa Coelho ◽  
Aurora Rodrigues ◽  
Helena Felgueiras ◽  
Pedro Oliveira ◽  
...  
Keyword(s):  
Early Onset ◽  
Sural Nerve ◽  
Nerve Biopsy ◽  
Amyloid Deposition ◽  
Familial Amyloid Polyneuropathy ◽  
Asymptomatic Carriers ◽  
Mutation Carriers ◽  
Amyloid Polyneuropathy ◽  
Myelinated Fibres ◽  
Fibre Loss

Abstract Familial amyloid polyneuropathy with the substitution of methionine for valine at position 30 in the TTR gene is the most common type of hereditary transthyretin amyloidosis. Although several authors have previously reported a size-dependent fibre loss, predominantly involving unmyelinated and small-diameter myelinated fibres, the mechanisms of nerve fibre loss have not been fully understood. In this study, we establish the morphometric pattern of peripheral neuropathy in patients with familial amyloid polyneuropathy and asymptomatic mutation carriers in the biopsies from our archive and correlated the pathological findings with clinical features. A total of 98 patients with familial amyloid polyneuropathy and 37 asymptomatic mutation carriers (TTR Val30Met mutation), aged between 17 and 84 years, who underwent sural nerve biopsy between 1981 and 2017 at Centro Hospitalar Universitário do Porto were studied. Thirty-one controls were included for comparison. The median age at nerve biopsy was 26.0 [interquartile range = 23.5–39.5] years for asymptomatic mutation carriers, 45.0 [35.0–60.0] years for patients with familial amyloid polyneuropathy and 44.0 [30.0–63.0] years for controls. The median duration between nerve biopsy and symptoms’ onset was 7.0 [3.3–11.8] years (range: 1–27 years) in the asymptomatic carriers. Most patients were in an earlier disease stage (93% with a polyneuropathy disability scale ≤2). Patients had loss of small and myelinated fibres compared with both asymptomatic carriers and controls (P &lt; 0.001), whereas asymptomatic carriers showed loss of small myelinated fibres when compared with controls (P &lt; 0.05). The loss of myelinated fibres increased with disease progression (P &lt; 0.001), and patients in more advanced clinical stage showed more frequent amyloid deposition in the nerve (P = 0.001). There was a positive correlation between large myelinated fibre density and time to symptoms’ onset in the asymptomatic carriers that developed early-onset form of the disease (r = 0.52, P &lt; 0.01). In addition, asymptomatic carriers with amyloid deposition already present in sural nerve biopsies developed symptoms earlier than those with no amyloid (P &lt; 0.01). In conclusion, this study confirms that the loss of small fibre size is an initial event in familial amyloid polyneuropathy, already present in asymptomatic gene carriers, starting several years before the onset of symptoms. We show for the first time that large myelinated fibres’ loss and amyloid deposition are pathological features that correlate independently with short period to the onset of symptoms for asymptomatic carriers that developed early-onset form of the disease. These findings are therapeutically relevant, as it would allow for a better interpretation of the role of disease-modifying agents in transthyretin familial amyloid polyneuropathy.

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