TY  - JOUR
A1  - Liedtke, Daniel
A1  - Hofmann, Christine
A1  - Jakob, Franz
A1  - Klopocki, Eva
A1  - Graser, Stephanie
T1  - Tissue-Nonspecific Alkaline Phosphatase—A Gatekeeper of Physiological Conditions in Health and a Modulator of Biological Environments in Disease
JF  - Biomolecules
N2  - Tissue-nonspecific alkaline phosphatase (TNAP) is a ubiquitously expressed enzyme that is best known for its role during mineralization processes in bones and skeleton. The enzyme metabolizes phosphate compounds like inorganic pyrophosphate and pyridoxal-5′-phosphate to provide, among others, inorganic phosphate for the mineralization and transportable vitamin B6 molecules. Patients with inherited loss of function mutations in the ALPL gene and consequently altered TNAP activity are suffering from the rare metabolic disease hypophosphatasia (HPP). This systemic disease is mainly characterized by impaired bone and dental mineralization but may also be accompanied by neurological symptoms, like anxiety disorders, seizures, and depression. HPP characteristically affects all ages and shows a wide range of clinical symptoms and disease severity, which results in the classification into different clinical subtypes. This review describes the molecular function of TNAP during the mineralization of bones and teeth, further discusses the current knowledge on the enzyme’s role in the nervous system and in sensory perception. An additional focus is set on the molecular role of TNAP in health and on functional observations reported in common laboratory vertebrate disease models, like rodents and zebrafish.
KW  - TNAP
KW  - hypophosphatasia
KW  - HPP
KW  - zebrafish
KW  - mineralization
KW  - ALPL
KW  - craniosynostosis
KW  - teeth
KW  - nervous system
Y1  - 2020
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-220096
SN  - 2218-273X
VL  - 10
IS  - 12
PB  - MDPI
ER  - 
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  -