Pathogenic Aspects of Inherited Platelet Disorders

2021 ◽  
Vol 41 (06) ◽  
pp. 460-468
Author(s):  
Doris Boeckelmann ◽  
Hannah Glonnegger ◽  
Kirstin Sandrock-Lang ◽  
Barbara Zieger
Keyword(s):  
Platelet Function ◽  
Function Analysis ◽  
Molecular Genetic ◽  
Molecular Genetic Analysis ◽  
Additional Surgery ◽  
Wound Healing Problems ◽  
Life Threatening ◽  
Platelet Disorders ◽  
Platelet Defects ◽  
Pulmonary Bleeding

AbstractInherited platelet disorders (IPDs) constitute a large heterogeneous group of rare bleeding disorders. These are classified into: (1) quantitative defects, (2) qualitative disorders, or (3) altered platelet production rate disorders or increased platelet turnover. Classically, IPD diagnostic is based on clinical phenotype characterization, comprehensive laboratory analyses (platelet function analysis), and, in former times, candidate gene sequencing. Today, molecular genetic analysis is performed using next-generation sequencing, mostly by targeting enrichment of a gene panel or by whole-exome sequencing. Still, the biochemical and molecular genetic characterization of patients with congenital thrombocytopathias/thrombocytopenia is essential, since postoperative or posttraumatic bleeding often occurs due to undiagnosed platelet defects. Depending upon the kind of surgery or trauma, this bleeding may be life-threatening, e.g., after tonsillectomy or in brain surgery. Undiagnosed platelet defects may lead to additional surgery, hysterectomy, pulmonary bleeding, and even resuscitation. In addition, these increased bleeding symptoms can lead to wound healing problems. Only specialized laboratories can perform the special platelet function analyses (aggregometry, flow cytometry, or immunofluorescent microscopy of the platelets); therefore, many IPDs are still undetected.

Genetics of inherited platelet disorders

2014 ◽  
Vol 34 (02) ◽  
pp. 133-141 ◽  
Author(s):  
M. Gothwal ◽  
K. Sandrock-Lang ◽  
B. Zieger
Keyword(s):  
Genetic Characterization ◽  
Clinical Phenotype ◽  
Molecular Genetic ◽  
Current Review ◽  
Gingival Bleeding ◽  
Life Threatening ◽  
Platelet Disorders ◽  
Platelet Defects ◽  
Molecular Genetic Characterization

SummaryThe current review describes inherited platelet disorders, illustrates their clinical phenotype and molecular genetic defects. Platelets are the key molecules mediating haemostasis via adhesion, activation and clot formation at the site of injury. The inherited platelet disorders can be classified according to their platelet defects: receptor/cytoskeleton defects, secretion disorder, and signal transduction defect.Patients with inherited thrombocytopathia present with mucous membrane bleedings (epistaxis, gingival bleeding) and may present with serious life threatening bleedings following surgery or trauma. Therefore, biochemical and molecular genetic characterization of inherited platelet disorders is important to understand these disorders and to support an efficient therapy.

scholarly journals Molecular Genetic Analysis of RB1 gene among Sudanese children with Retinoblastoma

2019 ◽  
Author(s):  
Nada O. Ibrahim ◽  
Mahgoub Saleem ◽  
Entesar Eltayeb ◽  
Salwa Mekki ◽  
Elteleb G. Elnaim ◽  
...  
Keyword(s):  
Functional Analysis ◽  
Genetic Analysis ◽  
In Silico ◽  
Molecular Genetic ◽  
Geographical Area ◽  
Good Prognosis ◽  
Molecular Genetic Analysis ◽  
Molecular Genetic Study ◽  
Genetic Sequencing ◽  
Life Threatening

BACKGROUNDRetinoblastoma (RB), the commonest early childhood intraocular tumor, is most often related to mutations in the RB1 gene with an incidence of 3% of all pediatric tumors. It has good prognosis if diagnosed early but it is life-threatening when diagnosed late.OBJECTIVETo study the Molecular Genetic Analysis of Retinoblastoma (RB) in Sudanese families.METHODSThirty one (n=31) clinically and histopathologically diagnosed cases of RB attending Makkah Eye Complex (MEC) Orbit clinic (Khartoum, Sudan) were included in this Molecular Genetic RB Analysis. Fresh blood samples extracted from seven RB patients and 15 close families for DNA extraction and PCR were sent for Genetic Sequencing and In silico approach for “Exon 18 mutations” which is one of the highly mutated exons worldwide.RESULTSThe majority of patients (41.9%) were below five years old. Females were 58.1%, males were 41.9%. Leukocoria was the commonest sign at presentation (41.9%). RB Unilaterality were in (77.4%) while Bilaterality in 19.4%. Both eyes were equally affected 50% each. The age at diagnosis time ranged from 0.02 to five years. Consanguinity of parents was very high (85.7%), the 1st degree cousins were less (28.6%) while the 2nd degree was high (57.1%). The patients’ ethnic background and geographical area were from seven different tribes; all belong to the Western Sudan. The molecular genetic study showed that exon 18 was free of mutation among the seven patients + their three relatives. The Functional Analysis and (SNPs) prediction study of exon 18 from NCBI data base showed that the various computational approaches used (SIFT, PolyPhen-2, I-mutant and Project hope) identified 16 reported mutations worldwide, three of which (rs137853292, rs375645171 and rs772068738) are major nsSNPs (non-synonymous) which might contribute to native RB1 protein malfunction and ultimately causing carcinoma.CONCLUSIONRB mainly affected children under five years and both sexes are equally affected. Unilaterality was predominant. Consanguinity plays a role in inheritance and the majority of patients were from Western Sudan. The most commonly detected deleterious mutations worldwide in exon 18 were not found in the Sudanese studies samples. Further screening for the highly reported mutations in exons 8, 10 and 14 or Next Generation Sequencing (NGS) are recommended. In silico tools are useful in studying the functional analysis of SNPs.

Platelet disorders

2021 ◽  
pp. 175573802199674
Author(s):  
Dominique Jade Forrest
Keyword(s):  
Primary Care ◽  
Clinical Outcomes ◽  
Platelet Function ◽  
Vital Role ◽  
Initial Assessment ◽  
Excessive Bleeding ◽  
Underlying Condition ◽  
Vast Array ◽  
Life Threatening ◽  
Platelet Disorders

Platelets play a vital role in haemostasis; therefore, an increase or decrease in levels or a disorder of platelet function can lead to symptoms such as easy bruising and excessive bleeding, particularly from mucocutaneous sites. Patients may also report symptoms associated with the underlying condition. Platelet disorders pose a particular challenge for primary care, due to the vast array of potential causes and clinical outcomes, ranging from little effect to life-threatening problems. Initial assessment in primary care should aim to identify those requiring urgent investigation or treatment, while also determining an underlying cause and potential complications.

scholarly journals Aggressive infantile myofibromatosis with intestinal involvement

2021 ◽  
Vol 8 (1) ◽  
Author(s):  
Tristan Römer ◽  
Norbert Wagner ◽  
Till Braunschweig ◽  
Robert Meyer ◽  
Miriam Elbracht ◽  
...  
Keyword(s):  
Kinase Inhibitor ◽  
Molecular Genetic ◽  
Molecular Genetic Analysis ◽  
Multiple Organ ◽  
Molecular Defect ◽  
Infantile Myofibromatosis ◽  
Case Presentation ◽  
Intestinal Involvement ◽  
Life Threatening ◽  
Fluctuating Course

Abstract Background Infantile myofibromatosis (IM) is the most common cause of multiple fibrous tumors in infancy. Multicentric disease can be associated with life-threatening visceral lesions. Germline gain-of-function mutations in PDGFRB have been identified as the most common molecular defect in familial IM. Case presentation We here describe an infant with PDGFRB-driven IM with multiple tumors at different sites, including intestinal polyposis with hematochezia, necessitating temporary chemotherapy. Conclusions PDGFRB-driven IM is clinically challenging due to its fluctuating course and multiple organ involvement in the first years of life. Early molecular genetic analysis is necessary to consider tyrosine kinase inhibitor treatment in case of aggressive visceral lesions.

Molecular Characterization and Genetic Diversity Study in F3 Population of Rice

2013 ◽  
Vol 20 (1-2) ◽  
pp. 1-8
Author(s):  
MM Rahman ◽  
L Rahman ◽  
SN Begum ◽  
F Nur
Keyword(s):  
Genetic Distance ◽  
Gene Diversity ◽  
Random Amplified Polymorphic Dna ◽  
Molecular Genetic ◽  
Molecular Genetic Analysis ◽  
Polymorphic Loci ◽  
Rice Genotypes ◽  
High Level ◽  
Genetic Diversity Study ◽  
Diversity Study

Random Amplified Polymorphic DNA (RAPD) assay was initiated for molecular genetic analysis among 13 F3 rice lines and their parents. Four out of 15 decamer random primers were used to amplify genomic DNA and the primers yielded a total of 41 RAPD markers of which 37 were considered as polymorphic with a mean of 9.25 bands per primer. The percentage of polymorphic loci was 90.24. The highest percentage of polymorphic loci (14.63) and gene diversity (0.0714) was observed in 05-6 F3 line and the lowest polymorphic loci (0.00) and gene diversity (0.00) was found in 05-12 and 05-15 F3 lines. So, relatively high level of genetic variation was found in 05-6 F3 line and it was genetically more diverse compared to others. The average co-efficient of gene differentiation (GST) and gene flow (Nm) values across all the loci were 0.8689 and 0.0755, respectively. The UPGMA dendrogram based on the Nei’s genetic distance differentiated the rice genotypes into two main clusters: PNR-519, 05-19, 05-14, 05-12 and 05-17 grouped in cluster 1. On the other hand, Baradhan, 05-9, 05-13, 05-11, 05-5, 05-6, 05-1, 05-4, 05-15 and 05-25 were grouped in cluster 2. The highest genetic distance (0.586) was found between 05-4 and 05-17 F3 lines and they remain in different cluster.DOI: http://dx.doi.org/10.3329/pa.v20i1-2.16839 Progress. Agric. 20(1 & 2): 1 – 8, 2009

Coagulation parameters and platelet function analysis in patients with acromegaly

2015 ◽  
Author(s):  
Hamiyet Yilmaz Yasar ◽  
Mustafa Demirpence ◽  
Ayfer Colak ◽  
Banu Ozturk Ceyhan ◽  
Yusuf Temel ◽  
...  
Keyword(s):  
Platelet Function ◽  
Function Analysis ◽  
Coagulation Parameters

Diagnosis and Management of Cardiomyopathies – A Focus on Genetics, Cardiac Magnetic Resonance and Clinical Features

2011 ◽  
Vol 7 (3) ◽  
pp. 225
Author(s):  
Gianfranco Sinagra ◽  
Michele Moretti ◽  
Giancarlo Vitrella ◽  
Marco Merlo ◽  
Rossana Bussani ◽  
...  
Keyword(s):  
Clinical Practice ◽  
Cardiac Magnetic Resonance ◽  
Magnetic Resonance ◽  
Imaging Techniques ◽  
Molecular Genetic ◽  
Molecular Genetic Analysis ◽  
Routine Clinical Practice ◽  
Clinical Approach ◽  
Diagnosis And Management ◽  
Made In

In recent years, outstanding progress has been made in the diagnosis and treatment of cardiomyopathies. Genetics is emerging as a primary point in the diagnosis and management of these diseases. However, molecular genetic analyses are not yet included in routine clinical practice, mainly because of their elevated costs and execution time. A patient-based and patient-oriented clinical approach, coupled with new imaging techniques such as cardiac magnetic resonance, can be of great help in selecting patients for molecular genetic analysis and is crucial for a better characterisation of these diseases. This article will specifically address clinical, magnetic resonance and genetic aspects of the diagnosis and management of cardiomyopathies.

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