A new staging system for hereditary transthyretin amyloidosis in the era of specific amyloidosis therapies.

Objectives: Currently, there are two prognosis staging systems validated for transthyretin amyloidosis (ATTR). We sought to develop a new staging system dedicated to hereditary transthyretin amyloidosis (ATTRv) patients on specific treatments.

Methods And Results: A total of 258 patients diagnosed with ATTRv from two cardiac amyloidosis reference centres in France and Romania were stratified into three disease stages based on NT-proBNP, estimated glomerular filtration rate (eGFR) and global longitudinal strain (GLS).

Refined genotype-phenotype correlations in neurofibromatosis type 1 patients with point variants.

Background: Neurofibromatosis type 1 (NF1) is one of the most frequent genetic disorders. NF1 is caused by dominant loss-of-function pathogenic variants (PVs) of the tumour-suppressor gene , which encodes neurofibromin, a negative regulator of rat sarcoma proteins. NF1 is an autosomal dominant disorder with complete penetrance, but a highly variable expression.

Clinical and cognitive assessment in Friedreich ataxia clinical trials: a review.

Friedreich ataxia (FRDA) is the most common type of inherited ataxia. It is a neurodegenerative disorder characterized by progressive gait and limb ataxia, dysarthria, areflexia, and reduced proprioception and vibration sensation. Although a number of clinical trials have been conducted, there is currently no cure for this disease.

A phenotypic comparison of the Romanian and French ATTRv cohorts: Glu54Gln founder pathogenic variant vs the most common variants in Western Europe.

Aim And Methods: We conducted a retrospective observational study of the ATTRv heterozygous mutation frequency, phenotype, and all-cause mortality at two cardiac amyloidosis centers in Romania and France.

Results: 291 patients were included: 26 Glu54Gln (all Romanian), 200 Val122Ile, 47 Val30Met and 18 Ser77Tyr. On diagnosis, Gu54Gln patients were younger than Val122Ile or late-onset Val30Met (median age: 46 [42-50], 76 [71-80] and 70 [61-76], respectively; p < 0.

Improving genetic testing pathways for transthyretin amyloidosis in France: challenges and strategies.

Transthyretin amyloidosis (ATTR) is a severe and rare disease characterized by the progressive deposition of misfolded transthyretin proteins, causing irreversible organ damage. Transthyretin amyloidosis can present as a hereditary ATTR or acquired wild-type ATTR form. Genetic testing is critical for determining a hereditary predisposition and subsequently initiating appropriate family screening.

The French hypertrophic cardiomyopathy gene register: A systematic large gene screening for hypertrophic cardiomyopathy.

Background: Although the optimal approach is debated, systematic genetic screening for hypertrophic cardiomyopathy (HCM) is recommended.

Aims: The performance of this approach was tested in GEREMY, a HCM prospective observational French register.

Methods: Screening was based on a 12-gene panel, including the Fabry disease (GLA) and the transthyretin (TTR) genes.

Loss of phospholipase PLAAT3 causes a mixed lipodystrophic and neurological syndrome due to impaired PPARγ signaling.

Phospholipase A/acyltransferase 3 (PLAAT3) is a phospholipid-modifying enzyme predominantly expressed in neural and white adipose tissue (WAT). It is a potential drug target for metabolic syndrome, as Plaat3 deficiency in mice protects against diet-induced obesity. We identified seven patients from four unrelated consanguineous families, with homozygous loss-of-function variants in PLAAT3, who presented with a lipodystrophy syndrome with loss of fat varying from partial to generalized and associated with metabolic complications, as well as variable neurological features including demyelinating neuropathy and intellectual disability.

Comparison of cardiac involvement, extracardiac manifestations and outcomes between homozygote and heterozygote transthyretin p.Val142Ile (V122I) variant in patients with hereditary transthyretin amyloidosis: a cohort study.

Background: Hereditary transthyretin (ATTRv) p.Val142Ile (V122I) mutation is the most common inherited cause of cardiac amyloidosis and little is known about the phenotype and outcome of the rare homozygotic genotype. This study aimed to compare phenotypic characteristics and outcomes between heterozygous and homozygous patients with ATTRv V122I amyloidosis.

Pathological spectrum of hereditary transthyretin renal amyloidosis and clinicopathologic correlation: a French observational study.

Background: Cardiac and neurological involvements are the main clinical features of hereditary transthyretin (ATTRv) amyloidosis. Few data are available about ATTRv amyloid nephropathy (ATTRvN).

Methods: We retrospectively included 30 patients with biopsy-proven ATTRvN [V30M (26/30) including two domino liver recipients, S77Y (2/30), V122I (1/30) and S50R (1/30) variants] from two French reference centers.

Real-Life Evaluation of an Algorithm for the Diagnosis of Cardiac Amyloidosis.

Objective: To evaluate the real-life use of a modified Gillmore algorithm with a "one-stop-shop" approach, bone scintigraphy (BS), a monoclonal gammopathy test (GT), a salivary gland biopsy (SGB), and genetic testing performed at the same time for the diagnosis of cardiac amyloidosis at the French National Reference Centre for Cardiac Amyloidosis (Henri Mondor Hospital, Créteil, France).

Methods: This retrospective cohort study included a total of 1222 patients with suspected amyloidosis who underwent BS and GT between June 2008 and May 2019.

Results: Of 1222 patients, 349 had no cardiac uptake on BS and negative GT (BS-/GT-), 276 were BS-/GT positive (GT+), 420 patients were BS+/GT-, and 177 were BS+/GT+.

Prevalence and determinants of iron deficiency in cardiac amyloidosis.

Aims: Iron deficiency (ID) is common in patient with chronic heart failure (HF) and has been widely studied. In contrast, data concerning ID in cardiac amyloidosis (CA) are limited. Amyloidosis is a severe and fatal systemic disease, characterized by an accumulation of amyloid fibrils in various tissues/organs, including nerves, kidneys, gastrointestinal tract, and heart.

Describing mode of death in three major cardiac amyloidosis subtypes to improve management and survival.

Background: The three main cardiac amyloidosis (CA) types have different progression and prognosis. Little is known about the mode of death (MOD) which is commonly attributed to cardiovascular causes in CA. Improving MOD's knowledge could allow to adapt patient care.

(TTF1) germline mutation associated with pulmonary fibrosis and lung cancer.

https://bit.ly/3CkkXgD.

History of extracardiac/cardiac events in cardiac amyloidosis: prevalence and time from initial onset to diagnosis.

Aims: Cardiac amyloidosis (CA) has a poor prognosis which is aggravated by diagnostic delay. Amyloidosis extracardiac and cardiac events (AECE and ACE) may help improve CA diagnosis and typing. The aim of this study was to compare AECE and ACE between different CA types and assess their relationship with survival.