10 results on '"Przylepa K"'
Search Results
2. FGFR2 exon IIIa and IIIc mutations in Crouzon, Jackson-Weiss, and Pfeiffer syndromes: Evidence for missense changes, insertions, and a deletion due to alternative RNA splicing
- Author
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Meyers, G. A., Day, D., Goldberg, R., Daentl, D. L., Przylepa, K. A., Abrams, L. J., Graham Jr, J. M., Feingold, M., Moeschler, J. B., Rawnsley, E., Scott, A. F., and Ethylin Jabs
- Subjects
musculoskeletal diseases ,Male ,congenital, hereditary, and neonatal diseases and abnormalities ,Base Sequence ,Craniofacial Dysostosis ,DNA Mutational Analysis ,Molecular Sequence Data ,Receptor Protein-Tyrosine Kinases ,Exons ,Syndrome ,Acrocephalosyndactylia ,Receptors, Fibroblast Growth Factor ,Alternative Splicing ,Craniosynostoses ,Mutation ,Humans ,Female ,Amino Acid Sequence ,Genetic Testing ,Receptor, Fibroblast Growth Factor, Type 2 ,Research Article ,Sequence Deletion - Abstract
Fibroblast growth factor receptor 2 (FGFR2) mutations have been associated with the craniosynostotic conditions Crouzon, Jackson-Weiss, and Pfeiffer syndromes. Previously, mutations were described in the exons IIIa and IIIc, which form the extracellular, third immunoglobulin-like domain (IgIII) and adjacent linker regions, both of which are normally involved in ligand binding. For all three conditions, mutations were found in exon IIIc. Only in Crouzon syndrome were mutations identified in exon IIIa. In this study, 39 cases with one of these three conditions were screened for exon IIIa or IIIc mutations. Eleven mutations are reported in 17 unrelated cases. Mutations in exon IIIa are identified for not only Crouzon but also Jackson-Weiss and Pfeiffer syndromes. Four mutations in either exon IIIa or exon IIIc reported only in Crouzon syndrome are present also in one of the other two syndromes. Two insertions, one in exon IIIa in a Crouzon syndrome patient and the other in exon IIIc in a Pfeiffer syndrome patient, were observed. The latter mutation has the same alternative RNA splicing effect as a reported synonymous mutation for Crouzon syndrome. A missense mutation was detected in one Pfeiffer syndrome family in which two members had craniosynostosis without limb anomalies. The inter- and intrafamilial variability in expression of FGFR2 mutations suggests that these three syndromes, presumed to be clinically distinct, are instead representative of a spectrum of related craniosynostotic and digital disorders.
3. World views on shortage in nursing resource: Challenges and opportunities.
- Author
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Nydahl P, Borromeo RC, Carrigan T, Dokken H, Fischer U, Kocks A, Kolbe N, Luboeinski J, Przylepa K, Safari SR, Zimmermann M, and Franz S
- Subjects
- Humans, Germany, Philippines, United States, United Kingdom, Tanzania, Cross-Cultural Comparison, Emigration and Immigration statistics & numerical data, Workload, Education, Nursing organization & administration, Health Services Needs and Demand organization & administration, Refugees statistics & numerical data, Developing Countries
- Abstract
Background: Shortage in nursing resource results from the combination of a lack of nurses, an increased patient volume and workload, and other factors. This seems to be a worldwide phenomenon, leading to multiple health care related challenges and a decreased quality of care, but is different in extent in high- vs. low-income countries. An international perspective can alleviate challenges to keep our patients safe through increasing our health workers' safety., Purpose & Method: To exchange experiences with the shortage in nursing resource globally, an international online conference event was hosted. Speakers from Germany, the Philippines, Poland, Tanzania, the United Kingdom and the United States presented their national challenges and strategies to deal with this phenomenon., Results: Conference presentations included information about the health care systems, comparable numbers of hospital beds, nurses, and nursing education. Speakers reported challenges such as an imbalance between a high nurse vacancy rate and demands, but also war and refugees, high human immunodeficiency virus (HIV) and other infection rates, or nurses' migration to other countries; the solutions reported included buy-in from other countries, nurses-attracting projects such as Magnet hospitals, improved job opportunities like higher wages, career prospects, or improved education, and others., Conclusions: Shortage in nursing resource seems to be a global phenomenon. Nursing managers and researchers should exchange and communicate challenges and solutions continuously and cooperate globally., (Copyright © 2024. Published by Elsevier GmbH.)
- Published
- 2024
- Full Text
- View/download PDF
4. Subtle radiographic findings of achondroplasia in patients with Crouzon syndrome with acanthosis nigricans due to an Ala391Glu substitution in FGFR3.
- Author
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Schweitzer DN, Graham JM Jr, Lachman RS, Jabs EW, Okajima K, Przylepa KA, Shanske A, Chen K, Neidich JA, and Wilcox WR
- Subjects
- Acanthosis Nigricans etiology, Achondroplasia complications, Achondroplasia diagnostic imaging, Achondroplasia genetics, Amino Acid Substitution genetics, Craniofacial Dysostosis genetics, Female, Humans, Infant, Newborn, Male, Radiography, Receptor, Fibroblast Growth Factor, Type 3, Acanthosis Nigricans genetics, Achondroplasia diagnosis, Craniofacial Dysostosis complications, Protein-Tyrosine Kinases, Receptors, Fibroblast Growth Factor genetics
- Abstract
A unique type of craniofacial dysostosis, Crouzon syndrome with acanthosis nigricans (CAN), has been attributed to a specific substitution (Ala391Glu) in the fibroblast growth factor receptor 3 (FGFR3) gene. At birth, individuals with this disorder have craniosynostosis, ocular proptosis, midface hypoplasia, choanal atresia, hydrocephalus, and they experience the onset of acanthosis nigricans during childhood. We report three cases and compare the clinical characteristics of our cases with the previously reported cases of this disorder. Since the Ala391Glu substitution in FGFR3 is close to the substitutions in the transmembrane domain that result in achondroplasia, we carefully reviewed the skeletal findings in six patients. We identified subtle radiographic findings of achondroplasia in all six cases including narrow sacrosciatic notches, short vertebral bodies, lack of the normal increase in interpediculate distance from the upper lumbar vertebrae caudally, and broad, short metacarpals and phalanges. Even before acanthosis nigricans appears, the presence of choanal atresia and hydrocephalus in an individual with features of Crouzon syndrome should suggest the diagnosis of CAN, and subtle skeletal findings can lend further support to this diagnosis.
- Published
- 2001
5. Severe achondroplasia with developmental delay and acanthosis nigricans (SADDAN): phenotypic analysis of a new skeletal dysplasia caused by a Lys650Met mutation in fibroblast growth factor receptor 3.
- Author
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Bellus GA, Bamshad MJ, Przylepa KA, Dorst J, Lee RR, Hurko O, Jabs EW, Curry CJ, Wilcox WR, Lachman RS, Rimoin DL, and Francomano CA
- Subjects
- Female, Humans, Infant, Newborn, Lysine genetics, Male, Methionine genetics, Phenotype, Radiography, Receptor, Fibroblast Growth Factor, Type 3, Skull diagnostic imaging, Skull pathology, Acanthosis Nigricans genetics, Developmental Disabilities genetics, Osteochondrodysplasias genetics, Point Mutation, Protein-Tyrosine Kinases, Receptors, Fibroblast Growth Factor genetics
- Abstract
We previously discovered a novel missense mutation (Lys650Met) in the tyrosine kinase domain of the fibroblast growth factor receptor 3 (FGFR3) gene in four unrelated individuals with a condition we called "severe achondroplasia with developmental delay and acanthosis nigricans" (SADDAN) [Tavormina et al., 1999: Am. J. Hum. Genet. 64:722-731]. Here we present a more detailed clinical account of the SADDAN phenotype. The FGFR3 Lys650Met mutation results in severe disturbances in endochondral bone growth that approach and overlap those observed in thanatophoric dysplasia, type I. However, this mutation is most often compatible with survival into adulthood. Other unusual bone deformities, such as femoral bowing with reverse (i.e., posterior apex) tibial and fibular bowing and "ram's horn" bowing of the clavicle, are also seen in some patients. In addition to skeletal dysplasia, progressive acanthosis nigricans, and central nervous system structural anomalies, seizures and severe developmental delays are observed in surviving SADDAN patients. Despite its location within the same FGFR3 codon as the thanatophoric dysplasia type II mutation (Lys650Glu) and a similar effect on constitutive activation of the FGFR3 tyrosine kinase, the Lys650Met is not associated with cloverleaf skull or craniosynostosis.
- Published
- 1999
6. Fibroblast growth factor receptor 2 mutations in Beare-Stevenson cutis gyrata syndrome.
- Author
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Przylepa KA, Paznekas W, Zhang M, Golabi M, Bias W, Bamshad MJ, Carey JC, Hall BD, Stevenson R, Orlow S, Cohen MM Jr, and Jabs EW
- Subjects
- Acanthosis Nigricans genetics, Amino Acid Sequence, Base Sequence, Craniosynostoses genetics, DNA Primers chemistry, Exons, Female, Genes, Dominant, Humans, Male, Membrane Glycoproteins genetics, Molecular Sequence Data, Pedigree, Point Mutation, Receptor, Fibroblast Growth Factor, Type 2, Syndrome, Abnormalities, Multiple genetics, Receptor Protein-Tyrosine Kinases genetics, Receptors, Fibroblast Growth Factor genetics, Skin Abnormalities
- Abstract
Beare-Stevenson cutis gyrata syndrome (MIM 123790) is an autosomal dominant condition characterized by the furrowed skin disorder of cutis gyrata, acanthosis nigricans, craniosynostosis, craniofacial dysmorphism, digital anomalies, umbilical and anogenital abnormalities and early death. Many of these features are characteristic of some of the autosomal dominant craniosynostotic syndromes. Mutations in Crouzon, Jackson-Weiss, Pfeiffer and Apert syndromes have been reported in the FGFR2 extracellular domain. In Crouzon syndrome patients with acanthosis nigricans, a recurrent mutation occurs in the transmembrane domain of FGFR3. We now describe the detection of FGFR2 mutations in the Beare-Stevenson cutis gyrata syndrome. In three sporatic cases, a novel missense mutation was found causing an amino acid to be replaced by a cysteine; two had the identical Ty375Cys mutation in the transmembrane domain and one had a Ser372Cys mutation in the carboxyl-terminal end of the linker region between the immunoglobulin III-like (Iglll) and transmembrane domains. In two patients, neither of these mutations were found suggesting further genetic heterogeneity.
- Published
- 1996
- Full Text
- View/download PDF
7. FGFR2 exon IIIa and IIIc mutations in Crouzon, Jackson-Weiss, and Pfeiffer syndromes: evidence for missense changes, insertions, and a deletion due to alternative RNA splicing.
- Author
-
Meyers GA, Day D, Goldberg R, Daentl DL, Przylepa KA, Abrams LJ, Graham JM Jr, Feingold M, Moeschler JB, Rawnsley E, Scott AF, and Jabs EW
- Subjects
- Acrocephalosyndactylia genetics, Amino Acid Sequence, Base Sequence, DNA Mutational Analysis, Exons genetics, Female, Genetic Testing, Humans, Male, Molecular Sequence Data, Receptor, Fibroblast Growth Factor, Type 2, Sequence Deletion, Syndrome, Alternative Splicing, Craniofacial Dysostosis genetics, Craniosynostoses genetics, Mutation, Receptor Protein-Tyrosine Kinases genetics, Receptors, Fibroblast Growth Factor genetics
- Abstract
Fibroblast growth factor receptor 2 (FGFR2) mutations have been associated with the craniosynostotic conditions Crouzon, Jackson-Weiss, and Pfeiffer syndromes. Previously, mutations were described in the exons IIIa and IIIc, which form the extracellular, third immunoglobulin-like domain (IgIII) and adjacent linker regions, both of which are normally involved in ligand binding. For all three conditions, mutations were found in exon IIIc. Only in Crouzon syndrome were mutations identified in exon IIIa. In this study, 39 cases with one of these three conditions were screened for exon IIIa or IIIc mutations. Eleven mutations are reported in 17 unrelated cases. Mutations in exon IIIa are identified for not only Crouzon but also Jackson-Weiss and Pfeiffer syndromes. Four mutations in either exon IIIa or exon IIIc reported only in Crouzon syndrome are present also in one of the other two syndromes. Two insertions, one in exon IIIa in a Crouzon syndrome patient and the other in exon IIIc in a Pfeiffer syndrome patient, were observed. The latter mutation has the same alternative RNA splicing effect as a reported synonymous mutation for Crouzon syndrome. A missense mutation was detected in one Pfeiffer syndrome family in which two members had craniosynostosis without limb anomalies. The inter- and intrafamilial variability in expression of FGFR2 mutations suggests that these three syndromes, presumed to be clinically distinct, are instead representative of a spectrum of related craniosynostotic and digital disorders.
- Published
- 1996
8. Fibroblast growth factor receptor 3 (FGFR3) transmembrane mutation in Crouzon syndrome with acanthosis nigricans.
- Author
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Meyers GA, Orlow SJ, Munro IR, Przylepa KA, and Jabs EW
- Subjects
- Acanthosis Nigricans complications, Acanthosis Nigricans pathology, Adolescent, Amino Acid Sequence, Base Sequence, Cell Membrane chemistry, Craniofacial Dysostosis complications, DNA Mutational Analysis, Female, Genetic Heterogeneity, Humans, Male, Molecular Sequence Data, Receptor, Fibroblast Growth Factor, Type 3, Acanthosis Nigricans genetics, Craniofacial Dysostosis genetics, Point Mutation, Protein-Tyrosine Kinases, Receptors, Fibroblast Growth Factor genetics
- Abstract
Crouzon syndrome, an autosomal dominant condition characterized by craniosynostosis, ocular proptosis and midface hypoplasia, is associated with mutations in fibroblast growth factor receptor 2 (FGFR2) (refs 1-3). For example, we have identified 10 different mutations in the FGFR2 extracellular immunoglobulin III (IgIII) domain in 50% (16/32) of our Crouzon syndrome patients. All mutations described so far for other craniosynostotic syndromes with associated limb anomalies--Jackson-Weiss, Pfeiffer, and Apert--also occur in the extracellular domain of FGFR2, as well as FGFR1 for Pfeiffer syndrome. In contrast, only FGFR3 mutations have been reported in dwarfing conditions--achondroplasia, thanatophoric dysplasia, and hypochondroplasia. For achondroplasia, greater than 99% of mutations occur in the FGFR3 transmembrane domain. We now report the unexpected observation of a FGFR3 transmembrane domain mutation, Ala391Glu, in three unrelated families with Crouzon syndrome and acanthosis nigricans, a specific skin disorder of hyperkeratosis and hyperpigmentation. The association of non-dwarfing and even non-skeletal conditions with FGFR3 mutations reveals the potential for a wide range of FGFR pleiotropic effects as well as locus heterogeneity in Crouzon syndrome. Our study underscores the biologic complexity of the FGFR gene family.
- Published
- 1995
- Full Text
- View/download PDF
9. Chromosome breaks and fragile sites in leukemic bone marrow cells.
- Author
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Przylepa KA and Wenger SL
- Subjects
- Adolescent, Aged, Caffeine pharmacology, Cells, Cultured, Child, Child, Preschool, Chromosome Fragile Sites, Floxuridine pharmacology, Humans, Karyotyping, Middle Aged, Bone Marrow ultrastructure, Chromosome Aberrations, Chromosome Fragility, Leukemia genetics
- Abstract
Bone marrow cells from leukemic and nonleukemic patients were examined for chromosome breakage in cultures treated with fluorodeoxyuridine (FUdR) and FUdR plus caffeine. The results indicate that the leukemic cells have more chromosome breakage than the nonleukemic cells when thymidylic synthetase is inhibited by FUdR. Addition of caffeine did not enhance this chromosome breakage. These findings of enhanced breakage by FUdR exposure in vitro, nevertheless, may suggest that leukemic cells in general are more susceptible to breakage than normal cells, thereby predisposing the former to secondary chromosome rearrangements.
- Published
- 1988
- Full Text
- View/download PDF
10. Fragile sites in leukemic bone marrow cells.
- Author
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Przylepa KA and Wenger SL
- Subjects
- Chromosome Fragile Sites, Humans, Bone Marrow ultrastructure, Chromosome Fragility, Leukemia genetics
- Published
- 1988
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