Establishment of Various Specific Parameters for the Routine Diagnostics in Patients with Glanzmann Thrombasthenia

Abstract Purpose Consanguineous couples are at increased risk of being heterozygous for the same autosomal recessive (AR) disorder(s), with a 25% risk of affected offspring as a consequence. Until recently, comprehensive preconception carrier testing (PCT) for AR disorders was unavailable in routine diagnostics. Here we developed and implemented such a test in routine clinical care. Methods We performed exome sequencing (ES) for 100 consanguineous couples. For each couple, rare variants that could give rise to biallelic variants in offspring were selected. These variants were subsequently filtered against a gene panel consisting of ~2,000 genes associated with known AR disorders (OMIM-based). Remaining variants were classified according to American College of Medical Genetics and Genomics/Association for Molecular Pathology (ACMG/AMP) guidelines, after which only likely pathogenic and pathogenic (class IV/V) variants, present in both partners, were reported. Results In 28 of 100 tested consanguineous couples (28%), likely pathogenic and pathogenic variants not previously known in the couple or their family were reported conferring 25% risk of affected offspring. Conclusion ES-based PCT provides a powerful diagnostic tool to identify AR disease carrier status in consanguineous couples. Outcomes provided significant reproductive choices for a higher proportion of these couples than previous tests.

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Digital Lesions in Dogs: A Statistical Breed Analysis of 2912 Cases

Veterinary Sciences ◽

10.3390/vetsci8070136 ◽

2021 ◽

Vol 8 (7) ◽

pp. 136

Author(s):

Julia Maria Grassinger ◽

Andreas Floren ◽

Tobias Müller ◽

Argiñe Cerezo-Echevarria ◽

Christoph Beitzinger ◽

...

Keyword(s):

Bone Tumors ◽

Soft Tissue Sarcomas ◽

Benign Tumors ◽

Malignant Neoplasms ◽

Routine Diagnostics ◽

Mast Cell Tumors ◽

Neoplastic Processes ◽

Study Population ◽

Tumor Like Lesions ◽

Labrador Retrievers

Breed predispositions to canine digital neoplasms are well known. However, there is currently no statistical analysis identifying the least affected breeds. To this end, 2912 canine amputated digits submitted from 2014–2019 to the Laboklin GmbH & Co. KG for routine diagnostics were statistically analyzed. The study population consisted of 155 different breeds (most common: 634 Mongrels, 411 Schnauzers, 197 Labrador Retrievers, 93 Golden Retrievers). Non-neoplastic processes were present in 1246 (43%), tumor-like lesions in 138 (5%), and neoplasms in 1528 cases (52%). Benign tumors (n = 335) were characterized by 217 subungual keratoacanthomas, 36 histiocytomas, 35 plasmacytomas, 16 papillomas, 12 melanocytomas, 9 sebaceous gland tumors, 6 lipomas, and 4 bone tumors. Malignant neoplasms (n = 1193) included 758 squamous cell carcinomas (SCC), 196 malignant melanomas (MM), 76 soft tissue sarcomas, 52 mast cell tumors, 37 non-specified sarcomas, 29 anaplastic neoplasms, 24 carcinomas, 20 bone tumors, and 1 histiocytic sarcoma. Predisposed breeds for SCC included the Schnauzer (log OR = 2.61), Briard (log OR = 1.78), Rottweiler (log OR = 1.54), Poodle (log OR = 1.40), and Dachshund (log OR = 1.30). Jack Russell Terriers (log OR = −2.95) were significantly less affected by SCC than Mongrels. Acral MM were significantly more frequent in Rottweilers (log OR = 1.88) and Labrador Retrievers (log OR = 1.09). In contrast, Dachshunds (log OR = −2.17), Jack Russell Terriers (log OR = −1.88), and Rhodesian Ridgebacks (log OR = −1.88) were rarely affected. This contrasted with the well-known predisposition of Dachshunds and Rhodesian Ridgebacks to oral and cutaneous melanocytic neoplasms. Further studies are needed to explain the underlying reasons for breed predisposition or “resistance” to the development of specific acral tumors and/or other sites.

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Glanzmann thrombasthenia complicated by frequent myeloproliferative neoplasm‐related thromboembolism: thrombosis occurring regardless of αIIbβIII integrin deficiency

Clinical Case Reports ◽

10.1002/ccr3.4757 ◽

2021 ◽

Vol 9 (9) ◽

Author(s):

Roger E. G. Schutgens ◽

Rolf T. Urbanus

Keyword(s):

Myeloproliferative Neoplasm ◽

Glanzmann Thrombasthenia

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Implementation of TMA and digitalization in routine diagnostics of breast pathology

Apmis ◽

10.1111/j.1600-0463.2011.02871.x ◽

2012 ◽

Vol 120 (4) ◽

pp. 341-347 ◽

Cited By ~ 9

Author(s):

Henrik Holm Rossing ◽

Maj-Lis Møller Talman ◽

Anne-Vibeke Laenkholm ◽

Vera Timmermans Wielenga

Keyword(s):

Breast Pathology ◽

Routine Diagnostics

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Allogeneic stem cell transplantation for Glanzmann thrombasthenia

Pediatric Blood & Cancer ◽

10.1002/pbc.21888 ◽

2008 ◽

Vol 52 (5) ◽

pp. 682-683 ◽

Cited By ~ 12

Author(s):

M. Kashif Ishaqi ◽

M. El-Hayek ◽

Adam Gassas ◽

M. Khanani ◽

Omar Trad ◽

...

Keyword(s):

Stem Cell ◽

Stem Cell Transplantation ◽

Cell Transplantation ◽

Allogeneic Stem Cell Transplantation ◽

Glanzmann Thrombasthenia

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Correlations between Antibody Immune Responses at Different Mucosal Effector Sites Are Controlled by Antigen Type and Dosage

Infection and Immunity ◽

10.1128/iai.68.7.3830-3839.2000 ◽

2000 ◽

Vol 68 (7) ◽

pp. 3830-3839 ◽

Cited By ~ 34

Author(s):

Dörthe Externest ◽

Barbara Meckelein ◽

M. Alexander Schmidt ◽

Andreas Frey

Keyword(s):

Cholera Toxin ◽

Plasma Cells ◽

Immunoglobulin A ◽

Secretory Iga ◽

Enzyme Linked Immunosorbent Assay ◽

Routine Diagnostics ◽

Significant Relationships ◽

Serum Igg ◽

Mucosal Surfaces ◽

Secretory Immunoglobulin

ABSTRACT Monitoring specific secretory immunoglobulin A (IgA) responses in the intestines after mucosal immunization or infection is impeded by the fact that sampling of small intestinal secretions requires invasive methods not feasible for routine diagnostics. Since IgA plasma cells generated after intragastric immunization are known to populate remote mucosal sites as well, secretory IgA responses at other mucosal surfaces may correlate to those in the intestines and could serve as proxy measures for IgA secretion in the gut. To evaluate the practicability of this approach, mice were immunized intragastrically with 0.2, 2, and 20 mg of ovalbumin plus 10 μg of cholera toxin, and the antigen-specific local secretory IgA responses in duodenal, ileal, jejunal, rectal, and vaginal secretions, saliva, urine, and feces, as well as serum IgG and IgA responses were analyzed by enzyme-linked immunosorbent assay. Correlation analysis revealed significant relationships between serum IgG and IgA, urinary IgA, salivary IgA, and secretory IgA in duodenal, jejunal, ileal, and rectal secretions for the 0.2-mg but not for the 20-mg ovalbumin dose. Fecal samples were poor predictors for intestinal antiovalbumin IgA responses, and no correlations could be established for cholera toxin, neither between local anti-cholera toxin levels nor to the antiovalbumin responses. Thus, specific IgA in serum, saliva, or urine can serve as a predictor of the release of specific IgA at intestinal surfaces after intragastric immunization, but the lack of correlations for high ovalbumin doses and for cholera toxin indicates a strong dependency on antigen type and dosage for these relationships.

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