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Richard A. Spritz - One of the best experts on this subject based on the ideXlab platform.
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Letter: Misdiagnosis of "neurofibromatosis" in patients with Piebaldism.
Dermatology online journal, 2011Co-Authors: Richard A. SpritzAbstract:Miminal diagnostic criteria for the diagnosis of neurofibromatosis 1 (NF1) includes six or more cafe-au-lait macules plus axillary freckling. However, a recent report by Duarte et al claims co-occurrence of Piebaldism and NF1 using this minimal criteria. We assert that this is not an accurate conclusion because both of these pigmentary findings occur frequently in typical cases of Piebaldism.
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Deletion of the SLUG (SNAI2) gene results in human Piebaldism.
American journal of medical genetics. Part A, 2003Co-Authors: Manuel Sánchez-martín, Richard A. Spritz, Jesús Pérez-losada, Arancha Rodríguez-garcía, Belén González-sánchez, Bruce R Korf, W Kuster, Celia Moss, I Sánchez-garcíaAbstract:Slug is a zinc-finger neural crest transcription factor, encoded by the SLUG gene, which is critical for development of hematopoietic stem cells, germ cells, and melanoblasts in the mouse. In mouse, heterozygous and homozygous slug mutations result in anemia, infertility, white forehead blaze, and depigmentation of the ventral body, tail, and feet. This phenotype is very similar to the heterozygous W (KIT)-mutant mouse phenotype and to human Piebaldism, which is characterized by a congenital depigmented patches and poliosis (white forelock). To investigate the possibility that some cases of human Piebaldism might result from abnormalities of the human SLUG (SNAI2) gene, we carried out Southern blot analysis of the SLUG gene in 17 unrelated patients with Piebaldism, who lack apparent KIT mutations. Three of these patients had evident heterozygous deletions of the SLUG gene encompassing the entire coding region. Real-time PCR confirmed the deletion in all cases. Fluoresence in situ hybridization (FISH) of genomic SLUG probes to metaphase chromosomes independently confirmed the deletion in one of the cases. These findings indicate that some cases of human Piebaldism result from mutation of the SLUG gene on chromosome 8, and provide further strong evidence for the role of SLUG in the development of human melanocytes.
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Rapid Publication Deletion of the SLUG (SNAI2) Gene Results in Human Piebaldism
2003Co-Authors: Bruce R Korf, Richard A. Spritz, C. Moss, Wolfgang Küster, Hautklinik Der Philipps-universitatAbstract:Human Medical Genetics Program, University of Colorado Health Sciences Center, Denver, ColoradoSlug is a zinc-finger neural crest trans-cription factor, encoded by the SLUG gene,which is critical for development of hemato-poietic stem cells, germ cells, and melano-blasts in the mouse. In mouse, heterozygousand homozygous slug mutations result inanemia, infertility, white forehead blaze,anddepigmentationoftheventralbody,tail,and feet. This phenotype is very similar tothe heterozygous W (KIT)-mutant mousephenotype and to human Piebaldism, whichis characterized by a congenital depigmen-ted patches and poliosis (white forelock). Toinvestigate the possibility that some casesof human Piebaldism might result from ab-normalities of the human SLUG (SNAI2)gene, we carried out Southern blot analysisof the SLUG gene in 17 unrelated patientswith Piebaldism, who lack apparent KITmutations. Three of these patients had evid-ent heterozygous deletions of the SLUGgeneencompassingtheentirecodingregion.Real-time PCR confirmed the deletion in allcases. Fluoresence in situ hybridization(FISH) of genomic SLUG probes to meta-phase chromosomes independently confirm-ed the deletion in one of the cases. Thesefindings indicate that some cases of humanPiebaldismresultfrommutationoftheSLUGgene on chromosome 8, and provide furtherstrong evidence for the role of SLUG in thedevelopment of human melanocytes.
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Piebaldism with deafness: Molecular evidence for an expanded syndrome
American journal of medical genetics, 1998Co-Authors: Richard A. Spritz, Peter BeightonAbstract:In a South African girl of Xhosa stock with severe Piebaldism and profound congenital sensorineural deafness we identified a novel missense substitution at a highly conserved residue in the intracellular kinase domain of the KIT proto-oncogene, R796G. Though auditory anomalies have been observed in mice with dominant white spotting (W) due to KIT mutations, deafness is not typical in human Piebaldism. Thus, the occurrence of sensorineural deafness in this patient extends considerably the phenotypic range of Piebaldism due to KIT gene mutation in humans and tightens the clinical similarity between Piebaldism and the various forms of Waardenburg syndrome.
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Molecular Basis of Human Piebaldism
Journal of Investigative Dermatology, 1994Co-Authors: Richard A. SpritzAbstract:Piebaldism is an autosomal dominant genetic disorder of pigmentation characterized by congenital patches of white skin and hair that lack melanocytes. Piebaldism results from mutations of the KIT proto-oncogene, which encodes the cell-surface receptor transmembrane tyrosine kinase for an embryonic growth factor, Steel factor. Several pathologic mutations of the KIT gene have now been identified in different patients with Piebaldism. Correlation of these mutations with the associated piebald phenotypes has led to the recognition of a hierarchy of three classes of mutations that result in a graded series of piebald phenotypes, and to improved understanding of the mechanisms that underlie dominant genetic disorders.
Peter Beighton - One of the best experts on this subject based on the ideXlab platform.
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Piebaldism: an autonomous autosomal dominant entity.
Clinical genetics, 2008Co-Authors: Ingrid Winship, Karen Young, R Martell, Rajkumar Ramesar, Diana Curtis, Peter BeightonAbstract:Piebaldism is a disorder in which the major clinical features are patchy hypopigmentation of the skin and a white forelock. The manifestations of Piebaldism overlap with those of other genodermatoses, in particular the Waardenburg syndrome, and it is uncertain whether Piebaldism is a distinct entity. We have documented a family in which seven affected members in three generations have gross Piebaldism without any additional stigmata. The intrafamilial phenotypic consistency is suggestive that this autosomal dominant disorder has independent syndromic status. Linkage studies using conventional gene markers failed to identity the locus of the faulty gene.
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Piebaldism with deafness: Molecular evidence for an expanded syndrome
American journal of medical genetics, 1998Co-Authors: Richard A. Spritz, Peter BeightonAbstract:In a South African girl of Xhosa stock with severe Piebaldism and profound congenital sensorineural deafness we identified a novel missense substitution at a highly conserved residue in the intracellular kinase domain of the KIT proto-oncogene, R796G. Though auditory anomalies have been observed in mice with dominant white spotting (W) due to KIT mutations, deafness is not typical in human Piebaldism. Thus, the occurrence of sensorineural deafness in this patient extends considerably the phenotypic range of Piebaldism due to KIT gene mutation in humans and tightens the clinical similarity between Piebaldism and the various forms of Waardenburg syndrome.
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mutations of the kit mast stem cell growth factor receptor proto oncogene account for a continuous range of phenotypes in human Piebaldism
American Journal of Human Genetics, 1992Co-Authors: Richard A. Spritz, Stuart A. Holmes, Raj Ramesar, Jacquie Greenberg, D. Curtis, Peter BeightonAbstract:Abstract Piebaldism is a rare autosomal dominant disorder of pigmentation, characterized by congenital patches of white skin and hair from which melanocytes are absent. We have previously shown that Piebaldism can result from missense and frameshift mutations of the KIT proto-oncogene, which encodes the cellular receptor tyrosine kinase for the mast/stem cell growth factor. Here, we report two novel KIT mutations associated with human Piebaldism. A proximal frameshift is associated with a mild piebald phenotype, and a splice-junction mutation is associated with a highly variable piebald phenotype. We discuss the apparent relationship between the predicted impact of specific KIT mutations on total KIT-dependent signal transduction and the severity of the resultant piebald phenotypes.
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Mutations of the KIT (mast/stem cell growth factor receptor) proto-oncogene account for a continuous range of phenotypes in human Piebaldism.
American journal of human genetics, 1992Co-Authors: Richard A. Spritz, Stuart A. Holmes, Raj Ramesar, Jacquie Greenberg, D. Curtis, Peter BeightonAbstract:Abstract Piebaldism is a rare autosomal dominant disorder of pigmentation, characterized by congenital patches of white skin and hair from which melanocytes are absent. We have previously shown that Piebaldism can result from missense and frameshift mutations of the KIT proto-oncogene, which encodes the cellular receptor tyrosine kinase for the mast/stem cell growth factor. Here, we report two novel KIT mutations associated with human Piebaldism. A proximal frameshift is associated with a mild piebald phenotype, and a splice-junction mutation is associated with a highly variable piebald phenotype. We discuss the apparent relationship between the predicted impact of specific KIT mutations on total KIT-dependent signal transduction and the severity of the resultant piebald phenotypes.
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Hearing impairment and pigmentary disturbance.
Annals of the New York Academy of Sciences, 1991Co-Authors: Peter Beighton, Ingrid Winship, Karen Young, Rajkumar Ramesar, Diana Curtis, Jacquie Greenberg, Denis Viljoen, S. L. SellarsAbstract:Hearing impairment is a variable manifestation of several heritable conditions in which pigmentation of the skin or eyes is abnormal. Some of these disorders are well recognized although uncommon, while others are virtually private syndromes. Practical issues concerning the major conditions of this type are reviewed in this article on a basis of a survey of 4452 profoundly deaf children attending special schools in Southern Africa, together with investigations in affected families. The Waardenburg syndrome (WS), which is the most common deafness-depigmentation disorder, was present in 121 (2.7%) of the 4452 deaf scholars. Further studies in 7 multigeneration affected families confirmed phenotypic variability and indicated a need for internationally agreed diagnostic criteria. In 4 Cape Town families of mixed ancestry the WS-I gene was linked to the 2q37 locus, but in another large kindred no linkage could be demonstrated. Nonallelic heterogeneity is possible. There is uncertainty concerning possible interrelationship between WS and Piebaldism. The phenotypic consistency of a South African family in which 7 persons in 3 generations had gross Piebaldism in the absence of disturbance of hearing or involvement of the eyes and periorbital structures is suggestive that this disorder and WS are separate entities. Molecular investigations indicate that the gene for Piebaldism in this kindred is not situated at the WS-I locus 2q37. Deafness and hyperpigmentation are present in neurofibromatosis type II (acoustic neuromata) and the multiple lentigines syndrome, while retinal pigmentation is a feature of the Usher syndrome. This latter entity is apparently much less common in Southern Africa than in other parts of the world.
I Sánchez-garcía - One of the best experts on this subject based on the ideXlab platform.
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Deletion of the SLUG (SNAI2) gene results in human Piebaldism.
American journal of medical genetics. Part A, 2003Co-Authors: Manuel Sánchez-martín, Richard A. Spritz, Jesús Pérez-losada, Arancha Rodríguez-garcía, Belén González-sánchez, Bruce R Korf, W Kuster, Celia Moss, I Sánchez-garcíaAbstract:Slug is a zinc-finger neural crest transcription factor, encoded by the SLUG gene, which is critical for development of hematopoietic stem cells, germ cells, and melanoblasts in the mouse. In mouse, heterozygous and homozygous slug mutations result in anemia, infertility, white forehead blaze, and depigmentation of the ventral body, tail, and feet. This phenotype is very similar to the heterozygous W (KIT)-mutant mouse phenotype and to human Piebaldism, which is characterized by a congenital depigmented patches and poliosis (white forelock). To investigate the possibility that some cases of human Piebaldism might result from abnormalities of the human SLUG (SNAI2) gene, we carried out Southern blot analysis of the SLUG gene in 17 unrelated patients with Piebaldism, who lack apparent KIT mutations. Three of these patients had evident heterozygous deletions of the SLUG gene encompassing the entire coding region. Real-time PCR confirmed the deletion in all cases. Fluoresence in situ hybridization (FISH) of genomic SLUG probes to metaphase chromosomes independently confirmed the deletion in one of the cases. These findings indicate that some cases of human Piebaldism result from mutation of the SLUG gene on chromosome 8, and provide further strong evidence for the role of SLUG in the development of human melanocytes.
Albert Wolkerstorfer - One of the best experts on this subject based on the ideXlab platform.
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autologous cell suspension grafting in segmental vitiligo and Piebaldism a randomized controlled trial comparing full surface and fractional co2 laser recipient site preparations
British Journal of Dermatology, 2017Co-Authors: Janny E Lommerts, Arne A Meesters, L Komen, M W Bekkenk, M A De Rie, Rosalie M Luiten, Albert WolkerstorferAbstract:SummaryBackground Autologous noncultured cell suspension transplantation is an effective treatment for repigmentation in segmental vitiligo and Piebaldism. Full surface laser ablation is frequently used to prepare the recipient site before cell suspension transplantation, even though the optimal laser settings and ablation depth are unknown. Objectives To assess the efficacy and safety of less invasive recipient-site preparations. Methods In a randomized, observer-blinded, controlled trial we compared different recipient-site preparations before cell suspension transplantation in segmental vitiligo and Piebaldism. In each patient, we randomly allocated three CO2 laser recipient-site preparations (209 and 144 μm full surface, and fractional) and a control (no treatment) to four depigmentations. After 6 months we assessed repigmentation and side-effects. Results We included 10 patients with vitiligo (n = 3) and Piebaldism (n = 7). Compared with the control site, we found more repigmentation after full surface ablation at 209 μm (median 68·7%, P = 0·01) and 144 μm (median 58·3%, P = 0·007), but no repigmentation after fractional ablation (median 0·0%, P = 0·14). Conclusions Superficial full surface ablation with a depth of 144 μm is an effective recipient-site preparation before cell suspension transplantation, while fractional CO2 laser is not.
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optimising size and depth of punch grafts in autologous transplantation of vitiligo and Piebaldism a randomised controlled trial
Journal of Dermatological Treatment, 2017Co-Authors: L Komen, Rosalie M Luiten, Charlotte Vrijman, Cecilia A C Prinsen, J Wietze P Van Der Veen, Albert WolkerstorferAbstract:AbstractBackground: To date, autologous punch grafting appears to be the easiest and least expensive surgical technique for stable vitiligo and Piebaldism. Punch grafting is available worldwide, with no need for specialised instruments. However, no reliable data on efficacy and safety of different punch depths and punch sizes are available.Objective/methods: To compare the efficacy and safety of different punch depths and punch sizes in autologous punch grafting, a randomised controlled trial was performed in 33 patients with vitiligo or Piebaldism. In each patient, four depigmented regions were allocated to: 1.5 mm deep grafts, 1.5 mm superficial grafts, 1.0 mm deep grafts, and 1.0 mm superficial grafts. Primary outcome was the total pigmented surface area. Secondary outcomes were Patients’ Global Assessment (PGA) and side effects.Results: Six months after grafting, 1.5 mm grafts showed a significantly larger pigmented surface area compared to 1.0-mm grafts (p < 0.001), though more side effects as well. ...
Stuart A. Holmes - One of the best experts on this subject based on the ideXlab platform.
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Novel mutations and deletions of the KIT (steel factor receptor) gene in human Piebaldism.
American journal of human genetics, 1995Co-Authors: Kazuhiko Ezoe, Stuart A. Holmes, Christopher P. Bennett, Jean L. Bolognia, Louise Brueton, John Burn, Rafael Falabella, Emilia M. Gatto, Norihisa IshiiAbstract:Piebaldism is an autosomal dominant genetic disorder of pigmentation characterized by white patches of skin and hair. Melanocytes are lacking in these hypopigmented regions, the result of mutations of the KIT gene, which encodes the cell surface receptor for steel factor (SLF). We describe the analysis of 26 unrelated patients with Piebaldism-like hypopigmentation--17 typical patients, 5 with atypical clinical features or family histories, and 4 with other disorders that involve white spotting. We identified novel pathologic mutations or deletions of the KIT gene in 10 (59%) of the typical patients, and in 2 (40%) of the atypical patients. Overall, we have identified pathologic KIT gene mutations in 21 (75%) of 28 unrelated patients with typical Piebaldism we have studied. Of the patients without apparent KIT mutations, none have apparent abnormalities of the gene encoding SLF itself (MGF), and genetic linkage analyses in two of these families are suggestive of linkage of the piebald phenotype to KIT. Thus, most patients with typical Piebaldism appear to have abnormalities of the KIT gene.
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novel mutations of the kit mast stem cell growth factor receptor proto oncogene in human Piebaldism
Journal of Investigative Dermatology, 1993Co-Authors: Richard A. Spritz, Stuart A. Holmes, Peter Itin, Wolfgang KüsterAbstract:Piebaldism is an autosomal dominant genetic disorder of pigmentation characterized by congenital patches of white skin and hair that lack melanocytes. Piebaldism results from mutations of the KlT proto-oncogene, which encodes the cellular receptor transmembrane tyrosine kinase for mast/seem cell growth factor. Here we describe two novel KIT mutations associated with human Piebaldism. These amino acid substitutions, located in the most highly conserved sections of the KIT kinase domain, would be expected to dominant, negatively inhibit KIT-dependent signal transduction, resulting in aberrant melanocyte proliferation or migration during embryologic development.
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Novel Mutations of the KIT (Mast/Stem Cell Growth Factor Receptor) Proto-Oncogene in Human Piebaldism
The Journal of investigative dermatology, 1993Co-Authors: Richard A. Spritz, Stuart A. Holmes, Peter Itin, Wolfgang KüsterAbstract:Piebaldism is an autosomal dominant genetic disorder of pigmentation characterized by congenital patches of white skin and hair that lack melanocytes. Piebaldism results from mutations of the KlT proto-oncogene, which encodes the cellular receptor transmembrane tyrosine kinase for mast/seem cell growth factor. Here we describe two novel KIT mutations associated with human Piebaldism. These amino acid substitutions, located in the most highly conserved sections of the KIT kinase domain, would be expected to dominant, negatively inhibit KIT-dependent signal transduction, resulting in aberrant melanocyte proliferation or migration during embryologic development.
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mutations of the kit mast stem cell growth factor receptor proto oncogene account for a continuous range of phenotypes in human Piebaldism
American Journal of Human Genetics, 1992Co-Authors: Richard A. Spritz, Stuart A. Holmes, Raj Ramesar, Jacquie Greenberg, D. Curtis, Peter BeightonAbstract:Abstract Piebaldism is a rare autosomal dominant disorder of pigmentation, characterized by congenital patches of white skin and hair from which melanocytes are absent. We have previously shown that Piebaldism can result from missense and frameshift mutations of the KIT proto-oncogene, which encodes the cellular receptor tyrosine kinase for the mast/stem cell growth factor. Here, we report two novel KIT mutations associated with human Piebaldism. A proximal frameshift is associated with a mild piebald phenotype, and a splice-junction mutation is associated with a highly variable piebald phenotype. We discuss the apparent relationship between the predicted impact of specific KIT mutations on total KIT-dependent signal transduction and the severity of the resultant piebald phenotypes.
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dominant negative and loss of function mutations of the c kit mast stem cell growth factor receptor proto oncogene in human Piebaldism
American Journal of Human Genetics, 1992Co-Authors: Richard A. Spritz, Lutz B. Giebel, Stuart A. HolmesAbstract:Piebaldism is an autosomal dominant disorder of melanocyte development and is characterized by congenital white patches of skin and hair from which melanocytes are completely absent. A similar disorder of the mouse, "dominant white spotting" (W), results from mutations of the c-kit proto-oncogene, which encodes the cellular tyrosine kinase receptor for the mast/stem cell growth factor. We have identified c-kit gene mutations in three patients with Piebaldism. A missense substitution (Phe----Leu) at codon 584, within the tyrosine kinase domain, is associated with a severe piebald phenotype, whereas two different frameshifts, within codons 561 and 642, are both associated with a variable and relatively mild piebald phenotype. This is consistent with a possible "dominant negative" effect of missense c-kit polypeptides on the function of the dimeric receptor.