scholarly journals Investigação de Etiologia Genética nas Ataxias Neurodegenerativas: Recomendações do Grupo de Neurogenética do Centro Hospitalar São João, Portugal

2017 ◽  
Vol 30 (6) ◽  
pp. 502
Author(s):  
Tiago Gomes ◽  
Joana Guimaraes ◽  
Miguel Leão ◽  
Em nome do Grupo de Neurogenética do Centro Hospitalar São João
Keyword(s):  
Autosomal Recessive ◽  
Autosomal Dominant ◽  
Scientific Evidence ◽  
Genetic Diagnosis ◽  
Clinical History ◽  
International Consensus ◽  
Neurogenetic Disorders ◽  
Rational Plan ◽  
Rational Process

In recent decades, a long and increasing list of monogenic neurodegenerative ataxias has been identified, allowing for better characterization of the pathophysiology, phenotype and prognosis of this heterogeneous group of disorders, while also revealing potential new therapeutic targets. However, the heterogeneity and complexity of the genotype-phenotype relationships and the high costs of molecular genetics often make it difficult for clinicians to decide on a molecular investigation based on an unbiased rational plan. Clinical history is essential to guide the diagnostic workup, but often the phenotype does not hold enough specificity to allow for predicting the genotype. The Group of Neurogenetics of the Centro Hospitalar São João, a multidisciplinary team of neurologists and geneticists with special interest in neurogenetic disorders, devised consensus recommendations for the investigation of the genetic aetiology of neurodegenerative ataxias in clinical practice, based on international consensus documents (currently containing potentially outdated information) and published scientific evidence on this topic. At the time these recommendations were written, there were around 10 well described autosomal recessive loci and more than 27 autosomal dominant loci for neurodegenerative ataxias. This document covers, in a pragmatic way, the rational process used for the genetic diagnosis of neurodegenerative ataxias, with specific recommendations for the various groups of these heterogeneous diseases, per the Portuguese reality.

scholarly journals Investigação de Etiologia Genética nas Demências Neurodegenerativas: Recomendações do Grupo de Neurogenética do Centro Hospitalar São João

2016 ◽  
Vol 29 (10) ◽  
pp. 675
Author(s):  
João Massano ◽  
Miguel Leão ◽  
Carolina Garrett ◽  
On behalf of Grupo de Neurogenética do Centro Hospitalar São João
Keyword(s):  
Alzheimer Disease ◽  
Frontotemporal Dementia ◽  
Scientific Evidence ◽  
Genetic Diagnosis ◽  
Gene Mutations ◽  
Genetic Etiology ◽  
International Consensus ◽  
Group A ◽  
Neurogenetic Disorders ◽  
Neurodegenerative Dementias

In the past few years several gene mutations have been identified as causative of the most frequent neurodegenerative dementias (Alzheimer disease and frontotemporal dementia). These advances, along with the complex phenotype-genotype relationships and the costs associated with genetic testing, have often made it difficult for clinicians to decide with regard to a rational plan for the investigation of the genetic etiology of the degenerative dementias. The Centro Hospitalar São João Neurogenetics Group, a multidisciplinary team of Neurologists and Geneticists with special interest in neurogenetic disorders, devised consensus recommendations for the investigation of the genetic etiology of Alzheimer disease and frontotemporal dementia in clinical practice, based on international consensus documents (currently containing partly outdated information) and published scientific evidence on this topic. Alzheimerdisease may be caused by mutations in PSEN1, PSEN2 and APP. APOE genotyping is not recommended for the diagnostic or genetic counseling purposes in Alzheimer disease. Frontotemporal dementia may be caused by mutations in several genes such as c9orf72, PGRN, MAPT, TBK1, VCP, SQSTM1, and UBQLN2. This paper pragmatically approaches the process of genetic diagnosis in Alzheimer disease and frontotemporal dementia, with specific recommendations for both disorders.

scholarly journals Clinical and Immunological Features of Human BCL10 Deficiency

2021 ◽  
Author(s):  
Blanca Garcia Solis ◽  
Ana Van Den Rym ◽  
Jareb J. Pérez-Caraballo ◽  
Abdulwahab Al –Ayoubi ◽  
Lazaro Lorenzo ◽  
...  
Keyword(s):  
Autosomal Recessive ◽  
Respiratory Infections ◽  
Genetic Diagnosis ◽  
Additional Patient ◽  
Hematopoietic Stem ◽  
Recommended Treatment ◽  
History Of ◽  
Different Populations ◽  
Human Immune

Abstract The CARD-BCL10-MALT1 (CBM) complex is critical for the proper assembly of human immune responses. The clinical and immunological consequences of deficiencies in some of its components such as CARD9, CARD11, and MALT1 have been elucidated in detail. However, the scarcity of BCL10 deficient patients prevented gaining that knowledge for this genetic disease. Only two patients with BCL10 deficiency have been reported to date. Here we describe in more depth an additional patient with autosomal recessive BCL10 complete deficiency caused by a nonsense mutation that leads to a loss of expression (K63X). Using mass cytometry coupled with unsupervised clustering and machine learning computational methods, we obtained a thorough characterization of the consequences of BCL10 deficiency in different populations of leukocytes. We showed that in addition to the almost absence of memory B and T cells reported before, this patient display a reduction in NK, gdT, Tregs, and TFH cells. The patient suffered from recurrent respiratory infections since early in life, and showed a family history of lethal severe infectious diseases. Fortunately, hematopoietic stem-cell transplantation (HSCT) cured her. Overall, this report highlights the importance of early genetic diagnosis for the management of BCL10 deficient patients and HSCT as the recommended treatment to cured this disease.

scholarly journals Current concepts in the treatment of hereditary ataxias

2016 ◽  
Vol 74 (3) ◽  
pp. 244-252 ◽  
Author(s):  
Pedro Braga Neto ◽  
José Luiz Pedroso ◽  
Sheng-Han Kuo ◽  
C. França Marcondes Junior ◽  
Hélio Afonso Ghizoni Teive ◽  
...  
Keyword(s):  
Autosomal Recessive ◽  
Autosomal Dominant ◽  
Clinical Symptoms ◽  
Genetic Diagnosis ◽  
Symptomatic Treatment ◽  
Hereditary Ataxias ◽  
Disease Modifying Therapy ◽  
Progressive Ataxia ◽  
Cerebellar Ataxias ◽  
Disease Modifying

ABSTRACT Hereditary ataxias (HA) represents an extensive group of clinically and genetically heterogeneous neurodegenerative diseases, characterized by progressive ataxia combined with extra-cerebellar and multi-systemic involvements, including peripheral neuropathy, pyramidal signs, movement disorders, seizures, and cognitive dysfunction. There is no effective treatment for HA, and management remains supportive and symptomatic. In this review, we will focus on the symptomatic treatment of the main autosomal recessive ataxias, autosomal dominant ataxias, X-linked cerebellar ataxias and mitochondrial ataxias. We describe management for different clinical symptoms, mechanism-based approaches, rehabilitation therapy, disease modifying therapy, future clinical trials and perspectives, genetic counseling and preimplantation genetic diagnosis.

scholarly journals Characterization of the genetic heterogeneity of populations through the load of hereditary pathology

2020 ◽  
pp. 17-18
Author(s):  
Г.И. Ельчинова ◽  
В.В. Кадышев ◽  
Р.А. Зинченко
Keyword(s):  
Genetic Heterogeneity ◽  
Genetic Epidemiology ◽  
Autosomal Recessive ◽  
Autosomal Dominant ◽  
Archival Data ◽  
Krasnodar Region

На основании архивных данных лаборатории генетической эпидемиологии ФГБНУ «МГНЦ» по 11 российским популяциям предложен метод количественной оценки генетической гетерогенности популяций по грузу аутосомно-доминантной и аутосомно-рецессивной наследственной патологии. Показано, что наименьшей гетерогенностью характеризуется Краснодарский край, наибольшей - население Татарстана. On the basis of archival data from the laboratory of genetic epidemiology of the RCMG for 11 Russian populations, a method for quantifying the genetic heterogeneity of populations based on the load of autosomal dominant and autosomal recessive hereditary pathology is proposed. It is shown that the Krasnodar region is characterized by the least heterogeneity, and the population of Tatarstan is the largest.

scholarly journals Estudo Genético nas Distonias Primárias: Recomendações do Grupo de Neurogenética do Centro Hospitalar São João

2017 ◽  
Vol 30 (4) ◽  
pp. 340
Author(s):  
Ana Monteiro ◽  
João Massano ◽  
Miguel Leão ◽  
Carolina Garrett ◽  
Em nome do Grupo de Neurogenética do Centro Hospitalar São João
Keyword(s):  
Clinical Practice ◽  
Age Of Onset ◽  
Scientific Evidence ◽  
Low Frequency ◽  
Gene Mutations ◽  
Molecular Testing ◽  
International Consensus ◽  
Group A ◽  
Neurogenetic Disorders ◽  
The Cost

The primary dystonias are a particular group of dystonias of presumed genetic origin, with a wide age of onset and variable progression. The diagnosis is, therefore, a challenge and the issue of the genetic investigation presents frequently in clinical practice. In the past few years several gene mutations have been identified as causative of primary dystonias. The choice of molecular testing is complex, given the clinical specificities and low frequency of these entities and the cost of genetic testing. It must follow observation by specialized clinicians highly differentiated in this area and be supported by a rational plan of investigation. The Centro Hospitalar São João Neurogenetics Group, a multidisciplinary team of Neurologists and Geneticists with special interest in neurogenetic disorders, devised consensus recommendations for the investigation of the genetic etiology of the primary dystonias, based on international consensus documents and recent published scientific evidence. This manuscript adopts the new classification system for genetic movement disorders, allowing for its systematic and standardized use in clinical practice.

Can progression of autosomal dominant or autosomal recessive polycystic kidney disease be prevented?

2001 ◽  
Vol 21 (5) ◽  
pp. 430-440 ◽  
Author(s):  
Ira D. Davis ◽  
Katherine MacRae Dell ◽  
William E. Sweeney ◽  
Ellis D. Avner
Keyword(s):  
Kidney Disease ◽  
Polycystic Kidney Disease ◽  
Autosomal Recessive ◽  
Autosomal Dominant ◽  
Polycystic Kidney
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