TY  - JOUR
A1  - Manukjan, Georgi
A1  - Wiegering, Verena
A1  - Reindl, Tobias
A1  - Strauß, Gabriele
A1  - Klopocki, Eva
A1  - Schulze, Harald
A1  - Andres, Oliver
T1  - Novel variants in FERMT3 and RASGRP2 - Genetic linkage in Glanzmann-like bleeding disorders
JF  - Pediatric Blood & Cancer
N2  - Defects of platelet intracellular signaling can result in severe platelet dysfunction. Several mutations in each of the linked genes FERMT3 and RASGRP2 on chromosome 11 causing a Glanzmann‐like bleeding phenotype have been identified so far. We report on novel variants in two unrelated pediatric patients with severe bleeding diathesis—one with leukocyte adhesion deficiency type III due to a homozygous frameshift in FERMT3 and the other with homozygous variants in both, FERMT3 and RASGRP2 . We focus on the challenging genetic and functional variant assessment and aim to accentuate the risk of obtaining misleading results due to the phenomenon of genetic linkage.
KW  - bleding disorders other than hemophilia
KW  - hematology
KW  - hemostasis and thrombosis
KW  - platelet disorders
Y1  - 2020
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-208129
VL  - 67
IS  - 2
ER  - 
TY  - JOUR
A1  - Laukner, Anna
A1  - Truchet, Laura
A1  - Manukjan, Georgi
A1  - Schulze, Harald
A1  - Langbein-Detsch, Ines
A1  - Mueller, Elisabeth
A1  - Leeb, Tosso
A1  - Kehl, Alexandra
T1  - Effects of cocoa genotypes on coat color, platelets and coagulation parameters in French Bulldogs
JF  - Genes
N2  - A nonsense variant in HPS3, c.2420G>A or p.Trp807*, was recently discovered as the cause for a brown coat color termed cocoa in French Bulldogs. Here, we studied the genotype–phenotype correlation regarding coat color in HPS3 mutant dogs that carried various combinations of mutant alleles at other coat color genes. Different combinations of HPS3, MLPH and TYRP1 genotypes resulted in subtly different shades of brown coat colors. As HPS3 variants in humans cause the Hermansky–Pudlak syndrome type 3, which in addition to oculocutaneous albinism is characterized by a storage pool deficiency leading to bleeding tendency, we also investigated the phenotypic consequences of the HPS3 variant in French Bulldogs on hematological parameters. HPS3 mutant dogs had a significantly lowered platelet dense granules abundance. However, no increased bleeding tendencies in daily routine were reported by dog owners. We therefore conclude that in dogs, the phenotypic effect of the HPS3 variant is largely restricted to pigmentation. While an effect on platelet morphology is evident, we did not obtain any indications for major health problems associated with the cocoa coat color in French Bulldogs. Further studies will be necessary to definitely rule out very subtle effects on visual acuity or a clinically relevant bleeding disorder.
KW  - Canis lupus familiaris
KW  - dog
KW  - thrombocyte
KW  - pigmentation
KW  - hematology
KW  - platelet
Y1  - 2021
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-242745
SN  - 2073-4425
VL  - 12
IS  - 7
ER  -