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Steven E.r. Hovius - One of the best experts on this subject based on the ideXlab platform.
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Preaxial Polydactyly of the foot Clinical and genetic implications for the orthopedic practice based on a literature review and 76 patients
Acta orthopaedica, 2017Co-Authors: Elise B. Burger, Steven E.r. Hovius, Martijn Baas, A. Jeannette M. Hoogeboom, Christianne A. Van NieuwenhovenAbstract:Background and purpose - Preaxial Polydactyly of the foot is a rare malformation and clinicians are often unfamiliar with the associated malformations and syndromes. In order to give guidelines for diagnostics and referral to a clinical geneticist, we provide an overview of the presentation using a literature review and our own patient population. Patients and methods - The literature review was based on the Human Phenotype Ontology (HPO) project. From the HPO dataset, all phenotypes describing preaxial Polydactyly were obtained and related diseases were identified and selected. An overview was generated in a heatmap, in which the phenotypic contribution of 12 anatomical groups to each disease is displayed. Clinical cases were obtained from our hospital database and were reviewed in terms of phenotype, genotype, heredity, and diagnosed syndromes. Results - From the HPO dataset, 21 diseases were related to preaxial Polydactyly of the foot. The anatomical groups with the highest phenotypic contribution were lower limb, upper limb, and craniofacial. From our clinical database, we included 76 patients with 9 different diseases, of which 27 had a GLI3 mutation. Lower limb malformations (n = 55), upper limb malformations (n = 59), and craniofacial malformations (n = 32) were most frequently observed. Malformations in other anatomical groups were observed in 27 patients. Interpretation - Preaxial Polydactyly of the foot often presents with other upper and lower limb malformations. In patients with isolated preaxial Polydactyly of the foot, referral to a clinical geneticist is not mandatory. In patients with additional malformations, consultation with a clinical geneticist is recommended. When additional limb malformations are present, analysis of GLI3 is most feasible.
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a classification system of radial Polydactyly inclusion of triphalangeal thumb and triplication
Journal of Hand Surgery (European Volume), 2008Co-Authors: Michiel J Zuidam, Ruud W. Selles, Michael Ananta, Jetteke Runia, Steven E.r. HoviusAbstract:Purpose Radial Polydactyly is a congenital anomaly with a wide range of manifestations. Current classifications do not have the capacity to classify all different types of radial Polydactyly when combined with triphalangeal components. The objective of this study was to test an adjusted classification and nomenclature that allows classification of triphalangeal components and triplication in radial Polydactyly. Methods Patients from 1993 to 2006 with radial Polydactyly (N = 104), a total of 121 affected hands, were identified from the hospital database. All x-rays were carefully examined and classified according to the existing classifications for radial Polydactyly and a modified classification. In the modified nomenclature, Wassel's level of duplication is preserved. Type VII and VIII are assigned for partial or complete duplication of the carpal bones according to Buck-Gramcko. Triplication and triphalangeal components can be assigned to each type of radial Polydactyly by suffixes. Symphalangism, deviation, and hypoplasia can also be classified. Triplication on different levels of the thumb is classified by determining and including the different types of the original Wassel classification. Results Eighteen thumbs could not be classified according to existing classifications for radial Polydactyly with triphalangeal components or triplication. Using the proposed classification, all patients could be classified. Conclusions We propose a modified classification that is a practical and utilitarian scheme for nomenclature of radial Polydactyly and that may assist comparison of treatment outcomes and individual cases. Type of study/level of evidence Diagnostic II.
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clinical and genetic studies on 12 preaxial Polydactyly families and refinement of the localisation of the gene responsible to a 1 9 cm region on chromosome 7q36
Journal of Medical Genetics, 1999Co-Authors: J. Zguricas, Henk C. Heus, Nurten Akarsu, Guido J. Breedveld, Estela Moralesperalta, Bertus Kuyt, Ethem F Mumcu, Wendela F Bakker, Simon P J Kay, Steven E.r. HoviusAbstract:Polydactyly is the most frequently observed congenital hand malformation with a prevalence between 5 and 19 per 10 000 live births. It can occur as an isolated disorder, in association with other hand/foot malformations, or as a part of a syndrome, and is usually inherited as an autosomal dominant trait. According to its anatomical location, Polydactyly can be generally subdivided into pre- and postaxial forms. Recently, a gene responsible for preaxial Polydactyly types II and III, as well as complex polysyndactyly, has been localised to chromosome 7q36. In order to facilitate the search for the underlying genetic defect, we ascertained 12 additional families of different ethnic origin affected with preaxial Polydactyly. Eleven of the kindreds investigated could be linked to chromosome 7q36, enabling us to refine the critical region for the preaxial Polydactyly gene to a region of 1.9 cM. Our findings also indicate that radial and tibial dysplasia/aplasia can be associated with preaxial Polydactyly on chromosome 7q36. Combining our results with other studies suggests that all non-syndromic preaxial polydactylies associated with triphalangism of the thumb are caused by a single genetic locus, but that there is genetic heterogeneity for preaxial Polydactyly associated with duplications of biphalangeal thumbs. Comparison of the phenotypic and genetic findings of different forms of preaxial Polydactyly is an important step in analysing and understanding the aetiology and pathogenesis of these limb malformations. Keywords: preaxial Polydactyly; chromosome 7q36; localisation
Nurten Akarsu - One of the best experts on this subject based on the ideXlab platform.
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Homozygous feature of isolated triphalangeal thumb-preaxial Polydactyly linked to 7q36: no phenotypic difference between homozygotes and heterozygotes.
Clinical genetics, 2009Co-Authors: Cn Semerci, F Demirkan, M Özdemir, E Biskin, B Akin, H Bagci, Nurten AkarsuAbstract:Preaxial Polydactyly is a common limb malformation in humans with variable clinical expression. Different types of triphalangeal thumb-preaxial Polydactyly phenotypes were mapped to the chromosome 7q36 region. We studied a large Turkish family of 69 individuals, of whom 22 individuals were affected. In all, 11 affected family members were clinically and radiologically evaluated. All affected individuals had a triphalangeal thumb and a preaxial (hypoplastic) extra digit bilaterally, with minimal intrafamilial variation. No feet involvement was observed. Linkage and haplotype analyses using 20 informative meioses confirmed the 7q36 region contained the LIMBR1 gene. Maximum logarithm of the odds (LOD) scores were obtained with DNA markers D7S550 and D7S2423. We have further identified a novel C to T alteration at position 4909 bp in the critical zone of polarizing activity regulatory sequence (ZRS) region, in the intron 5, of the LMBR1 gene. One affected male with homozygous status and no phenotypic difference from affected family members with heterozygous status represented the first homozygote case of the triphalangeal thumb-preaxial Polydactyly phenotype.
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heterozygotes
'Wiley', 2009Co-Authors: Cn Semerci, Biskin E., Akin B., Bagci H., Demirkan F, Ozdemir M, Nurten AkarsuAbstract:Preaxial Polydactyly is a common limb malformation in humans with variable clinical expression. Different types of triphalangeal thumb-preaxial Polydactyly phenotypes were mapped to the chromosome 7q36 region. We studied a large Turkish family of 69 individuals, of whom 22 individuals were affected. In all, 11 affected family members were clinically and radiologically evaluated. All affected individuals had a triphalangeal thumb and a preaxial (hypoplastic) extra digit bilaterally, with minimal intrafamilial variation. No feet involvement was observed. Linkage and haplotype analyses using 20 informative meioses confirmed the 7q36 region contained the LIMBR1 gene. Maximum logarithm of the odds (LOD) scores were obtained with DNA markers D7S550 and D7S2423. We have further identified a novel C to T alteration at position 4909 bp in the critical zone of polarizing activity regulatory sequence (ZRS) region, in the intron 5, of the LMBR1 gene. One affected male with homozygous status and no phenotypic difference from affected family members with heterozygous status represented the first homozygote case of the triphalangeal thumb-preaxial Polydactyly phenotype
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clinical and genetic studies on 12 preaxial Polydactyly families and refinement of the localisation of the gene responsible to a 1 9 cm region on chromosome 7q36
Journal of Medical Genetics, 1999Co-Authors: J. Zguricas, Henk C. Heus, Nurten Akarsu, Guido J. Breedveld, Estela Moralesperalta, Bertus Kuyt, Ethem F Mumcu, Wendela F Bakker, Simon P J Kay, Steven E.r. HoviusAbstract:Polydactyly is the most frequently observed congenital hand malformation with a prevalence between 5 and 19 per 10 000 live births. It can occur as an isolated disorder, in association with other hand/foot malformations, or as a part of a syndrome, and is usually inherited as an autosomal dominant trait. According to its anatomical location, Polydactyly can be generally subdivided into pre- and postaxial forms. Recently, a gene responsible for preaxial Polydactyly types II and III, as well as complex polysyndactyly, has been localised to chromosome 7q36. In order to facilitate the search for the underlying genetic defect, we ascertained 12 additional families of different ethnic origin affected with preaxial Polydactyly. Eleven of the kindreds investigated could be linked to chromosome 7q36, enabling us to refine the critical region for the preaxial Polydactyly gene to a region of 1.9 cM. Our findings also indicate that radial and tibial dysplasia/aplasia can be associated with preaxial Polydactyly on chromosome 7q36. Combining our results with other studies suggests that all non-syndromic preaxial polydactylies associated with triphalangism of the thumb are caused by a single genetic locus, but that there is genetic heterogeneity for preaxial Polydactyly associated with duplications of biphalangeal thumbs. Comparison of the phenotypic and genetic findings of different forms of preaxial Polydactyly is an important step in analysing and understanding the aetiology and pathogenesis of these limb malformations. Keywords: preaxial Polydactyly; chromosome 7q36; localisation
Sajid Malik - One of the best experts on this subject based on the ideXlab platform.
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Complex postaxial Polydactyly types A and B with camptodactyly, hypoplastic third toe, zygodactyly and other digit anomalies caused by a novel GLI3 mutation.
European journal of medical genetics, 2017Co-Authors: Sara Mumtaz, Aslihan Tolun, Esra Yıldız, Karmoon Lal, Sajid MalikAbstract:Polydactyly is a phenotypically and genetically highly heterogeneous limb malformation with preaxial and postaxial subtypes and subtypes A and B. Most Polydactyly entities are associated with GLI3 mutation. We report on 10 affected individuals from a large Pakistani kindred initially evaluated as a possible new condition. The phenotype is postaxial Polydactyly types A and B associated with zygodactyly, postaxial webbing of toes and additional features not previously reported for isolated Polydactyly such as camptodactyly, hypoplasia of third toe, and wide space between hallux and second toe. Hypothesizing that the disorder could have resulted from a mutation in a novel gene responsible for Polydactyly, we launched a genetic investigation. By linkage mapping and exome sequencing in the most severe case, we identified novel heterozygous frameshift mutation NM_000168.5 (GLI3): c.3635delG (p.(Gly1212Alafs*18)) but did not detect any other possibly deleterious mutation that could explain the unusual features of camptodactyly, hypoplasia of third toe and wide space between first and second toes. Our findings further expand the phenotypic variability of GLI3 Polydactyly. We also present a review of GLI3-associated isolated limb anomalies, which indicates that GLI3 mutation leads primarily to two well-established Polydactyly types: postaxial types A and B and crossed Polydactyly type I. In addition, a variety of other minor digit anomalies generally accompany Polydactyly, and there is no straightforward genotype-Polydactyly phenotype correlation.
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A novel ZRS mutation in a Balochi tribal family with triphalangeal thumb, pre-axial Polydactyly, post-axial Polydactyly, and syndactyly.
American Journal of Medical Genetics Part A, 2012Co-Authors: Julia E. Vandermeer, Nadav Ahituv, Muhammad Afzal, Saadia Alyas, Sayedul Haque, Sajid MalikAbstract:Limb malformations are one of the most common types of human congenital malformations. Mutations in the ZRS enhancer of Sonic Hedgehog are thought to be responsible for preaxial Polydactyly in multiple independent families. Here, we describe a large Balochi tribal family from Southern Punjab, Pakistan, with a variable set of limb malformations and a novel ZRS mutation. The family has a limb phenotype characterized by triphalangeal thumb, preaxial Polydactyly and postaxial Polydactyly. There is also a high degree of phenotypic heterogeneity with less common clinical findings in the affected family members that include osseous syndactyly of forth-fifth fingers, clinodactyly, hypoplasia of mesoaxial fingers, and bifid halluces. The presentation in most of the affected patients was bilateral and symmetrical. A heterozygous C>A mutation at position 287 of the ZRS enhancer (chr7:156,584,283; hg19) was detected in all affected subjects and is absent from four unaffected family members, 42 unrelated samples and multiple databases of human variation. Combined, these results identify a novel ZRS287 C>A mutation which leads to a variable spectrum of limb phenotypes.
Matthias Steinwachs - One of the best experts on this subject based on the ideXlab platform.
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Characterization of Polydactyly chondrocytes and their use in cartilage engineering
Scientific Reports, 2019Co-Authors: Emma Cavalli, Clara Levinson, Matthias Hertl, Nicolas Broguiere, Anja Gerstenberg, Gian M. Salzmann, Oscar Bruck, Satu Mustjoki, Daniel M. Weber, Matthias SteinwachsAbstract:Treating cartilage injuries and degenerations represents an open surgical challenge. The recent advances in cell therapies have raised the need for a potent off-the-shelf cell source. Intra-articular injections of TGF-β transduced Polydactyly chondrocytes have been proposed as a chronic osteoarthritis treatment but despite promising results, the use of gene therapy still raises safety concerns. In this study, we characterized infant, Polydactyly chondrocytes during in vitro expansion and chondrogenic re-differentiation. Polydactyly chondrocytes have a steady proliferative rate and re-differentiate in 3D pellet culture after up to five passages. Additionally, we demonstrated that Polydactyly chondrocytes produce cartilage-like matrix in a hyaluronan-based hydrogel, namely transglutaminase cross-linked hyaluronic acid (HA-TG). We utilized the versatility of TG cross-linking to augment the hydrogels with heparin moieties. The heparin chains allowed us to load the scaffolds with TGF-β1, which induced cartilage-like matrix deposition both in vitro and in vivo in a subcutaneous mouse model. This strategy introduces the possibility to use infant, Polydactyly chondrocytes for the clinical treatment of joint diseases.
Amelia Villa - One of the best experts on this subject based on the ideXlab platform.
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short rib Polydactyly syndrome and pericentric inversion of chromosome 4
American Journal of Medical Genetics, 1994Co-Authors: Miguel Urioste, Maria Luisa Martinezfrias, E Bermejo, Dolores Romero, Carmen Nieto, N. Jiménez, Amelia VillaAbstract:We report on a newborn infant with clinical and radiological manifestations of some type of short rib-Polydactyly syndrome who died soon after birth. Chromosomal studies on peripheral blood lymphocytes and chondrocytes demonstrated an apparently balanced pericentric inversion of chromosome 4 (present in the mother also). This association may have occurred by chance but, if not, the chromosomal breakpoints could interrupt the gene responsible for short rib-Polydactyly syndromes, or else be related to the mechanism of short rib-Polydactyly syndromes. © 1994 Wiley-Liss, Inc.
