scholarly journals Genetic Techniques Used in the Diagnosis of Inherited Platelet Disorders

2019 ◽  
Vol 45 (07) ◽  
pp. 685-694 ◽  
Author(s):  
Andrew D. Mumford ◽  
Sarah K. Westbury
Keyword(s):  
Genetic Analysis ◽  
Genetic Disorders ◽  
Genetic Diagnosis ◽  
Inherited Disorders ◽  
Recent Advances ◽  
Platelet Number ◽  
Genetic Techniques ◽  
Platelet Disorders ◽  
And Function

AbstractRecent advances in genetic analysis are bringing huge benefits to patients with rare genetic disorders, including those with inherited disorders of platelet number and function. Modern clinical hematological practice now has a range of genetic techniques available to enable the precision diagnosis of inherited platelet disorders (IPDs). There are some features of this disparate group of inherited disorders that present specific challenges to establishing an accurate genetic diagnosis. This review aims to introduce the techniques that are relevant for the genetic diagnosis of IPDs and will discuss the key considerations necessary for their application to the clinic.

scholarly journals Whole exome analysis of primary immunodeficiency

2018 ◽  
Vol 22 (5) ◽  
pp. 620-626
Author(s):  
E. S. Rahmani ◽  
Н. Azarpara ◽  
M. Karimipoor ◽  
Н. Rahimi
Keyword(s):  
Primary Immunodeficiency ◽  
Genetic Disorders ◽  
Single Gene ◽  
Correct Diagnosis ◽  
Severe Combined Immunodeficiency ◽  
Genetic Diagnosis ◽  
Cost Effective ◽  
Mendelian Disease ◽  
Inherited Disorders ◽  
Whole Exome

The human primary immunodeficiency diseases (PIDs) refer to a rare heterogeneous group of single-gene inherited disorders causing malfunctions in the immune system, and thus the affected patients have a predisposition to severe life-threatening infections. The heterogeneous nature of PIDs, which involves at list 300 different genes, makes diagnosis of the disease a complex issue. Although studies revealed that six million people have a kind of PID, but due to a complex diagnosis procedure many affected individuals have not gotten a correct diagnosis. However, thanks to advancing in the DNA sequencing method and availability of sophisticated sequencers molecular characterization of genetic disorders have been revolutionized. The whole exome sequencing (WES) method can help clinicians detect Mendelian disease and other complex genetic disorders. The presented study used WES to investigate two infants with symptoms of primary immunodeficiency including hemophagocytic lymphohistio­cytosis (HLH) and severe combined immunodeficiency (SCID). It has been shown that the HLH patient had a mutation in the UNC13D gene (NM_199242.2:c.627delT), and the SCID patient had a mutation in the RAG1 gene (NM_000448.2:c.322C>G). It has been demonstrated that WES is a fast and cost-effective method facilitating genetic diagnosis in PID sufferers.

scholarly journals A Novel Non-frameshift ADA Deletion Detected by Whole Exome Sequencing in an Iranian Family with Severe Combined Immunodeficiency

2020 ◽  
Author(s):  
Taravat Talebi ◽  
Alirezai Biglari ◽  
Mohammad Shahroeei ◽  
Majid Changi-Ashtiani ◽  
Hossein Dinmohammadi ◽  
...  
Keyword(s):  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Novel Mutation ◽  
Genetic Disorders ◽  
Severe Combined Immunodeficiency ◽  
Genetic Diagnosis ◽  
Sample Volume ◽  
Combined Immunodeficiency ◽  
Whole Exome ◽  
And Function

Severe combined immunodeficiency (SCID) comprises a heterogeneous group of genetic disorders caused by early defects in the development and function of T cells. Other lymphocyte lineages (B and/or natural killer cells) are variably affected. With a worldwide frequency of approximately 1:50,000 live births, SCID may result from diverse mutations in over 16 genes. Whole-exome sequencing (WES) provides an opportunity for parallel screening of all those genes. This approach is also useful for genetic diagnosis in parents whose infant expired before genetic testing. Here, we describe a heterozygous novel non-frameshift deletion (c.587_598del p.196_199del) in the adenosine deaminase (ADA) gene identified by WES in healthy parents of an expired child with SCID. The mutation was subsequently confirmed to be homozygous in the deceased baby whose left-over blood sample volume was insufficient for direct WES analysis. In conclusion, we here describe a novel mutation in ADA, a well-known SCID gene.  

Bleeding Time in Rats: A Comparison of Different Experimental Conditions

1982 ◽  
Vol 48 (01) ◽  
pp. 108-111 ◽  
Author(s):  
Elisabetta Dejana ◽  
Silvia Villa ◽  
Giovanni de Gaetano
Keyword(s):  
Platelet Function ◽  
Bleeding Time ◽  
Platelet Dysfunction ◽  
Experimental Conditions ◽  
Platelet Number ◽  
Coagulation Defects ◽  
Tail Tip ◽  
And Function ◽  
Storage Pool Disease ◽  
Type Of Anaesthesia

SummaryThe tail bleeding time (BT) in rats definitely varies according to the method applied. Of the various variables that may influence BT, we have evaluated the position (horizontal or vertical) of the tail, the environment (air or saline), the temperature (4°, 23° or 37° C) and the type of anaesthesia. Transection of the tail tip cannot be used to screen drugs active on platelet function since it is sensitive to coagulation defects. Template BT in contrast is not modified by heparin and is sensitive to defects of platelet number and function (“storage pool disease”, dipyridamole-like drugs, exogenous prostacyclin). In contrast the test fails to detect aspirin-induced platelet dysfunction. The evidence reported indicates that thromboxane A2-prostacyclin balance is not a factor regulating BT. Aspirin treatment however may be a precipitating factor when associated with other abnormalities of platelet function.Template BT is a valid screening test for platelet disorders and for antiplatelet drugs.

Case report: a child with cystic fibrosis and phenylketonuria

2020 ◽  
Vol 1 (2) ◽  
pp. 38-44
Author(s):  
Irina V. Vakhlova ◽  
Anastasia D. Kazachina ◽  
Olga A. Beglyanina
Keyword(s):  
Cystic Fibrosis ◽  
Case Report ◽  
Clinical Practice ◽  
Neonatal Screening ◽  
Genetic Disorders ◽  
Epileptiform Activity ◽  
Autism Spectrum ◽  
Speech Development ◽  
Inherited Disorders ◽  
Congenital Diseases

Background. In the international clinical practice there have been occasional reports of phenylketonuria (PKU) and cystic fibrosis (CF) found simultaneously in the same patient. Both PKU and CF are the inherited disorders characterized by autosomal recessive type of inheritance. Currently the combination of two or more inherited disorders in one patient is considered to be a clinical rarity.Case description. This is a clinical case of two genetic disorders, CF and PKU, combined in a 5-year old patient who had been followed up since birth. Owing to implementation of neonatal screening for inherited and congenital diseases into clinical practice, during the first month of life the infant was diagnosed with CF (diagnostically significant elevation of immunoreactive trypsin [IRT] at the initial [163.2 ng/mL] and repeat testing on day 21 of life [138.7 ng/mL]) and PKU (phenylalanine [PA] level 15.9 mg/dL). Both disorders have been confirmed by genetic tests, i.e., homozygous DelF508 mutation was found in the cystic fibrosis transmembrane conductance regulator (CFTR) gene, and P281L mutation in the phenylalanine hydroxylase (PAH) gene was also present in homozygous state. Child’s parents strictly adhered to dietary and treatment recommendations. By the age of 5 years the child developed symptoms of neurological disorder and disorder of the respiratory system, cognitive impairment and delay in speech development, subclinical epileptiform activity with high risk of epilepsy, and chronic inflammation of the respiratory tract.Conclusion. This case report demonstrates the important role of neonatal screening in early diagnosis and timely start of therapy, and underscores the importance of continuous medication in such genetic disorders as CF and PKU. On the whole, such approach brings about a relative preservation of functioning of the most affected organs and systems. By the age of 5 years the child does not form bronchiectases, shows no signs of chronic hypoxia, nutritional deficiency or pronounced neurologic deficit, and is at low risk for the development of autism spectrum disorder. At the same time, the larger scale and longer-term observations are required in order to make the unequivocal conclusions about the prognosis of these diseases under conditions of modern-day medical follow-up.

scholarly journals Rare skeletal disorders: a multidisciplinary postnatal approach to diagnosis and management

2021 ◽  
Vol 171 (5-6) ◽  
pp. 94-101
Author(s):  
Nina-Katharina Walleczek ◽  
Kristina Förster ◽  
Martina Seyr ◽  
Nadja Kadrnoska ◽  
Jennifer Kolar ◽  
...  
Keyword(s):  
Management Approach ◽  
Healthcare Team ◽  
Inherited Disorders ◽  
Skeletal Involvement ◽  
Diagnosis And Management ◽  
Huge Impact ◽  
Growth Center ◽  
Genetic Techniques ◽  
Skeletal Disorders ◽  
Diagnostic Flowchart

SummarySkeletal disorders are inherited disorders with significant skeletal involvement and most of them are rare or extremely rare. Based on the clinical, radiological and genetic phenotype, the group of skeletal disorder comprises more than 450 different and highly heterogeneous disorders. In skeletal disorders rapid and precise diagnoses are urgently needed for patient care and are based on the combination of clinical, radiological and genetic analysis. Novel genetic techniques have revolutionized diagnostics and have a huge impact on counseling of patients and families. Disease-specific long-term management in a multidisciplinary healthcare team in highly specialized centers is recommended to optimize care for these patients. Here we describe a multidisciplinary postnatal approach for the diagnosis and management of patients and families with rare skeletal disorders at the Vienna Bone and Growth Center. We discuss the value of a multidisciplinary diagnostic and management approach in the postnatal setting and provide a diagnostic flowchart for rare skeletal disorders.

Effect of Live-Fire Training Drills on Firefighters’ Platelet Number and Function

2011 ◽  
Vol 15 (2) ◽  
pp. 233-239 ◽  
Author(s):  
Denise L. Smith ◽  
Steven J. Petruzzello ◽  
Eric Goldstein ◽  
Uzma Ahmad ◽  
Krishnarao Tangella ◽  
...  
Keyword(s):  
Platelet Number ◽  
And Function

scholarly journals Recent advances in understanding and managing psoriatic arthritis

F1000Research ◽  
2016 ◽  
Vol 5 ◽  
pp. 2670 ◽  
Author(s):  
Dafna D. Gladman
Keyword(s):  
Psoriatic Arthritis ◽  
Early Diagnosis ◽  
Clinical Laboratory ◽  
Joint Damage ◽  
Screening Tools ◽  
Therapeutic Interventions ◽  
Joint Disease ◽  
New Therapeutic Approaches ◽  
Recent Advances ◽  
And Function

This article reviews recent advances in psoriatic arthritis (PsA) over the past several years with emphasis on early diagnosis, better understanding of pathogenesis, and new therapeutic approaches. Early diagnosis is important, since people who present late do not fare as well. There are a number of clinical, laboratory, and ultrasound features that can help identify patients destined to develop PsA, and several screening tools have been developed. It is recognized that genetic and epigenetic factors, as well as T cells and cytokines, play a role in the pathogenesis of PsA, and several targets have been identified for therapeutic interventions. New therapies have been developed and tested in PsA and have been found to be highly effective for both skin and joint manifestations of the disease. The expectation is that, in the future, PsA patients will be treated early and more aggressively and that there will not be significant progression of joint damage. Moreover, with effective treatment of the skin and joint disease and management of risk factors for the comorbidities, we can expect to reduce their occurrence and further reduce the excess mortality and reduced quality of life and function in these patients.

Attitudes Toward Pre-implantation Genetic Diagnosis (PGD) for Genetic Disorders Among Potential Users in Malaysia

2015 ◽  
Vol 22 (1) ◽  
pp. 133-146 ◽  
Author(s):  
Angelina Patrick Olesen ◽  
Siti Nurani Mohd Nor ◽  
Latifah Amin
Keyword(s):  
Genetic Disorders ◽  
Genetic Diagnosis
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