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Harefuah Jun 2023Piebaldism is the dominantly inherited skin disorder clinically characterized by congenital stable and well circumscribed patches of leukoderma (depigmented skin) of...
Piebaldism is the dominantly inherited skin disorder clinically characterized by congenital stable and well circumscribed patches of leukoderma (depigmented skin) of ventral distribution, involving central forehead, frontal chest and abdomen and central portion of limbs, and by localized poliosis (white hair). Inherited or de novo mutations in proto-oncogene KIT, encoding the transmembrane tyrosine kinase receptor c-kit, underly the majority of piebaldism cases. Piebaldism is a disorder characterized by incomplete penetrance and variable expressivity.
Topics: Humans; Piebaldism; Proto-Oncogene Proteins c-kit; Cafe-au-Lait Spots
PubMed: 37394438
DOI: No ID Found -
Indian Dermatology Online Journal 2024[This retracts the article on p. 144 in vol. 3, PMID: 23130293.].
[This retracts the article on p. 144 in vol. 3, PMID: 23130293.].
PubMed: 38845665
DOI: 10.4103/idoj.idoj_305_24 -
Klinische Monatsblatter Fur... Dec 2022
Topics: Humans; Waardenburg Syndrome; Piebaldism; Albinism, Oculocutaneous
PubMed: 34571549
DOI: 10.1055/a-1610-9690 -
BMC Genomics Apr 2022Leaf colour mutations are universally expressed at the seedling stage and are ideal materials for exploring the chlorophyll biosynthesis pathway, carotenoid metabolism...
BACKGROUND
Leaf colour mutations are universally expressed at the seedling stage and are ideal materials for exploring the chlorophyll biosynthesis pathway, carotenoid metabolism and the flavonoid biosynthesis pathway in plants.
RESULTS
In this research, we analysed the different degrees of albinism in apple (Malus domestica) seedlings, including white-leaf mutants (WM), piebald leaf mutants (PM), light-green leaf mutants (LM) and normal leaves (NL) using bisulfite sequencing (BS-seq) and RNA sequencing (RNA-seq). There were 61,755, 79,824, and 74,899 differentially methylated regions (DMRs) and 7566, 3660, and 3546 differentially expressed genes (DEGs) identified in the WM/NL, PM/NL and LM/NL comparisons, respectively.
CONCLUSION
The analysis of the methylome and transcriptome showed that 9 DMR-associated DEGs were involved in the carotenoid metabolism and flavonoid biosynthesis pathway. The expression of different transcription factors (TFs) may also influence the chlorophyll biosynthesis pathway, carotenoid metabolism and the flavonoid biosynthesis pathway in apple leaf mutants. This study provides a new method for understanding the differences in the formation of apple seedlings with different degrees of albinism.
Topics: Albinism; Carotenoids; Chlorophyll; Epigenome; Flavonoids; Gene Expression Profiling; Gene Expression Regulation, Plant; Malus; Plant Leaves; Seedlings; Transcriptome
PubMed: 35439938
DOI: 10.1186/s12864-022-08535-3 -
Chaos (Woodbury, N.Y.) Jan 2022The classical Turing mechanism containing a long-range inhibition and a short-range self-enhancement provides a type of explanation for the formation of patterns on body...
The classical Turing mechanism containing a long-range inhibition and a short-range self-enhancement provides a type of explanation for the formation of patterns on body surfaces of some vertebrates, e.g., zebras, giraffes, and cheetahs. For other type of patterns (irregular spots) on body surfaces of some vertebrates, e.g., loaches, finless eels, and dalmatian dogs, the classical Turing mechanism no longer applies. Here, we propose a mechanism, i.e., the supercritical pitchfork bifurcation, which may explain the formation of this type of irregular spots, and present a method to quantify the similarity of such patterns. We assume that, under certain conditions, the only stable state of "morphogen" loses its stability and transitions to two newly generated stable states with the influence of external noise, thus producing such ruleless piebald patterns in space. The difference between the competitiveness of these two states may affect the resulting pattern. Moreover, we propose a mathematical model based on this conjecture and obtain this type of irregular patterns by numerical simulation. Furthermore, we also study the influence of parameters in the model on pattern structures and obtain the corresponding pattern structures of some vertebrates in nature, which verifies our conjecture.
Topics: Animals; Computer Simulation; Dogs; Models, Biological; Models, Theoretical; Vertebrates
PubMed: 35105114
DOI: 10.1063/5.0070325 -
Stem Cell Research & Therapy May 2021Griscelli syndrome type 2 (GS-2) is a rare, autosomal recessive immune deficiency syndrome caused by a mutation in the RAB27A gene, which results in the absence of a...
BACKGROUND
Griscelli syndrome type 2 (GS-2) is a rare, autosomal recessive immune deficiency syndrome caused by a mutation in the RAB27A gene, which results in the absence of a protein involved in vesicle trafficking and consequent loss of function of in particular cytotoxic T and NK cells. Induced pluripotent stem cells (iPSC) express genes associated with pluripotency, have the capacity for infinite expansion, and can differentiate into cells from all three germ layers. They can be induced using integrative or non-integrative systems for transfer of the Oct4, Sox2, Klf4, and cMyc (OSKM) transcription factors. To better understand the pathophysiology of GS-2 and to test novel treatment options, there is a need for an in vitro model of GS-2.
METHODS
Here, we generated iPSCs from 3 different GS-2 patients using lentiviral vectors. The iPSCs were characterized using flow cytometry and RT-PCR and tested for the expression of pluripotency markers. In vivo differentiation to cells from all three germlines was tested using a teratoma assay. In vitro differentiation of GS-2 iPSCs into hematopoietic stem and progenitor cells was done using Op9 feeder layers and specified media.
RESULTS
All GS-2 iPSC clones displayed a normal karyotype (46XX or 46XY) and were shown to express the same RAB27A gene mutation that was present in the original somatic donor cells. GS-2 iPSCs expressed SSEA1, SSEA4, TRA-1-60, TRA-1-81, and OCT4 proteins, and SOX2, NANOG, and OCT4 expression were confirmed by RT-PCR. Differentiation capacity into cells from all three germ layers was confirmed using the teratoma assay. GS-2 iPSCs showed the capacity to differentiate into cells of the hematopoietic lineage.
CONCLUSIONS
Using the lentiviral transfer of OSKM, we were able to generate different iPSC clones from 3 GS-2 patients. These cells can be used in future studies for the development of novel treatment options and to study the pathophysiology of GS-2 disease.
Topics: Cell Differentiation; Feeder Cells; Hematopoietic Stem Cell Transplantation; Humans; Induced Pluripotent Stem Cells; Kruppel-Like Factor 4; Lymphohistiocytosis, Hemophagocytic; Piebaldism; Primary Immunodeficiency Diseases
PubMed: 33985578
DOI: 10.1186/s13287-021-02364-z -
Animal Biotechnology Apr 2023An investigation was carried out on Deoni animals of western India to study the allelic and genotypic frequencies in coding region of TYR gene as well as gene expression...
An investigation was carried out on Deoni animals of western India to study the allelic and genotypic frequencies in coding region of TYR gene as well as gene expression profile. The animals were grouped according to age, gender, strain and intensity of partial albinism (low, medium and high). The present study revealed that the genotypic frequency of TYR gene across different strains, gender, age group and level of partial albinism was found to be non-significant for both exon-I and exon-II. The AB genotype in Balankya (0.70) was observed highest genotypic frequency followed by Wanera (0.55) and Shewara (0.55) strains. The genotypic frequency of AB and BB genotypes were observed highest in male and female, respectively. In exon-I, genotype frequency of AA genotype was found highest (0.55) in low level of partial albinism. The allelic frequencies in Shewara strain, male and low level of partial albinism were 0.75, 0.63 and 0.73, respectively. However, in exon-II genotype frequency of AB and BB was observed highest (0.70) in Wanera and Balankya strains followed by AA genotype in Shewara (0.50). The highest genotypic frequency of AA (0.87) and BB (0.50) were in male and female, respectively. The genotype frequency of AB genotype was found highest in all level of partial albinism. The allelic frequency was highest (0.85 for B allele) in Wanera strain, male (0.80 for A allele) and high level (0.60 for A allele) of particle albinism. The highly significant ( = 0.002) expression of tyrosinase gene was observed in young animals as compared to adult animals. The TYR gene expression was significantly ( = 0.047) higher in animals with low intensity of partial albinism followed by in the animals with medium and high intensity. Therefore, it is inferred that the TYR gene expression in young animals were high and as compared to the old animals of Deoni cattle breed.
Topics: Male; Cattle; Female; Animals; Monophenol Monooxygenase; Piebaldism; Genotype; India; Gene Expression; Cattle Diseases
PubMed: 34355636
DOI: 10.1080/10495398.2021.1953515 -
Acta Dermatovenerologica Croatica : ADC Aug 2020Piebaldism is a rare, autosomal dominant disorder characterized by the congenital absence of melanocytes in affected areas of the skin and hair. We report on a familial...
Piebaldism is a rare, autosomal dominant disorder characterized by the congenital absence of melanocytes in affected areas of the skin and hair. We report on a familial 4q12 deletion that involves the KIT gene and causes piebaldism in affected individuals. Whole-genome genotyping analysis of the proband using HumanCytoSNP-12v2.1 BeadChips (Illumina Inc., San Diego, CA, USA, revealed a 1.34-Mb microduplication of 1q21.1q21.2 and a 2.7-Mb microdeletion of 4q12. The analysis of the parents confirmed the paternal origin of the 4q12 microdeletion. The clinical and molecular findings in the proband and his affected relatives showed that the 2.7-Mb 4q12 microdeletion, the smallest microdeletion reported to date, causes isolated piebaldism due to the loss of the KIT gene.
Topics: Child; Female; Gene Deletion; Genotype; Humans; Male; Pedigree; Piebaldism; Proto-Oncogene Proteins c-kit
PubMed: 32876036
DOI: No ID Found -
Journal of Chemical Theory and... Oct 2022KIT is a type 3 receptor tyrosine kinase that plays a crucial role in cellular growth and proliferation. Mutations in KIT can dysregulate its active-inactive...
KIT is a type 3 receptor tyrosine kinase that plays a crucial role in cellular growth and proliferation. Mutations in KIT can dysregulate its active-inactive equilibrium. Activating mutations drive cancer growth, while deactivating mutations result in the loss of skin and hair pigmentation in a disease known as piebaldism. Here, we propose a method based on molecular dynamics and free energy calculations to predict the functional effect of KIT mutations. Our calculations may have important clinical implications by defining the functional significance of previously uncharacterized KIT mutations and guiding targeted therapy.
Topics: Humans; Mutation; Piebaldism; Proto-Oncogene Mas; Proto-Oncogene Proteins c-kit
PubMed: 36166736
DOI: 10.1021/acs.jctc.2c00526 -
Dermatology (Basel, Switzerland) 2023The autologous noncultured melanocyte keratinocyte transplant procedure (MKTP) has emerged as a popular grafting technique with proven efficacy for achieving...
BACKGROUND
The autologous noncultured melanocyte keratinocyte transplant procedure (MKTP) has emerged as a popular grafting technique with proven efficacy for achieving repigmentation. However, there remains no consensus regarding the optimal recipient-to-donor (RD) ratio required to achieve acceptable repigmentation. In this retrospective cohort study of 120 patients, we sought to examine whether expansion ratios impact the repigmentation success rates following MKTP.
RESULTS
A total of 69 patients (mean [SD] age was 32.4 [14.3] years, mean follow-up was 30.4 [22.5] months, 63.8% were male; 55% were dark-skinned individuals [Fitzpatrick IV-VI]) were included. The mean percent change in the Vitiligo Area Scoring Index (VASI) was 80.2 (±23.7; RD of 7.3) in patients with focal/segmental vitiligo (SV), 58.3 (±33.0; RD of 8.2) in those with non-segmental vitiligo (NSV), and 51.8 (±33.6; RD of 3.7) in those with leukoderma and piebaldism. Focal/SV was positively associated with a higher percent change in VASI (parameter estimate: 22.6, p value <0.005). In the SV/focal group, non-white patients had a higher RD ratio compared to White individuals (8.2 ± 3.4 vs. 6.0 ± 3.1, respectively, p value = 0.035).
DISCUSSION
In our study, we found that patients with SV were significantly more likely to achieve higher repigmentation rates compared to those with NSV. Although repigmentation rates were higher in the low expansion ratio group than in the high expansion ratio group, we did not observe a significant difference between the two groups.
CONCLUSION
MKTP is an effective therapy for restoring repigmentation in patients with stable vitiligo. Therapeutic response of vitiligo to MKTP appears to be influenced by the type of vitiligo, rather than a specific RD ratio.
Topics: Adolescent; Female; Humans; Male; Keratinocytes; Melanocytes; Piebaldism; Retrospective Studies; Treatment Outcome; Vitiligo; Transplantation, Autologous; Cell Transplantation; Young Adult; Adult
PubMed: 37231873
DOI: 10.1159/000530930