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Klinische Monatsblatter Fur... Dec 2022
Topics: Humans; Waardenburg Syndrome; Piebaldism; Albinism, Oculocutaneous
PubMed: 34571549
DOI: 10.1055/a-1610-9690 -
Ophthalmic Genetics Feb 2022Chromosome 4q deletions are rare disorders phenotypically characterized by several features. The most commonly described ocular abnormalities include unilateral...
BACKGROUND
Chromosome 4q deletions are rare disorders phenotypically characterized by several features. The most commonly described ocular abnormalities include unilateral microphthalmia with bilateral colobomata, blue sclerae with pigmented retinal clumps, hypermetropia, and a divergent squint.
PURPOSE
To report a case of 4q12 deletion with a singular retinal feature.
MATERIALS AND METHODS
Case report.
RESULTS
A 20-year-old Caucasian female with a history of poliosis, progressive appearance of small areas of skin depigmentation along trunk and limbs since birth and diagnosis of learning deficit was referred for a complete ocular examination. The genetic counseling showed microdeletion in the 4q12 region. An audiometric test was performed, showing a progressive bilateral neurosensorial hypoacusia. Ocular examination showed the presence of multifocal, tiny, whitish deposits in the posterior pole. Multimodal imaging defined the lesions as small elevations of the retinal pigment epithelium with slight hyper-autofluorescence and staining in the late phase of fluoresceine angiography (FA). Visual acuity was 20/20. The retinal findings did not change during the three-month follow-up.
CONCLUSIONS
Although the findings herein reported have never been described before in patients affected by 4q12 mutations, we do not exclude that they could represent a manifestation of the peculiar genetic asset of the patient, related to dysfunction in pigment epithelium/neuroretinal metabolic activity.
Topics: Adult; Chromosome Deletion; Female; Fluorescein Angiography; Humans; Multimodal Imaging; Retina; Retinal Pigment Epithelium; Tomography, Optical Coherence; Visual Acuity; Young Adult
PubMed: 34551660
DOI: 10.1080/13816810.2021.1978102 -
Piebaldism resulting from a novel deletion mutation of KIT gene in a five-generation Chinese family.Clinical and Experimental Dermatology Jan 2022
Topics: Asian People; Female; Humans; Infant; Pedigree; Piebaldism; Proto-Oncogene Proteins c-kit; Sequence Deletion
PubMed: 34374464
DOI: 10.1111/ced.14834 -
ELife Aug 2021Amino-terminal acetylation is catalyzed by a set of N-terminal acetyltransferases (NATs). The NatA complex (including X-linked Naa10 and Naa15) is the major...
Amino-terminal acetylation is catalyzed by a set of N-terminal acetyltransferases (NATs). The NatA complex (including X-linked Naa10 and Naa15) is the major acetyltransferase, with 40-50% of all mammalian proteins being potential substrates. However, the overall role of amino-terminal acetylation on a whole-organism level is poorly understood, particularly in mammals. Male mice lacking show no globally apparent in vivo amino-terminal acetylation impairment and do not exhibit complete embryonic lethality. Rather nulls display increased neonatal lethality, and the majority of surviving undersized mutants exhibit a combination of hydrocephaly, cardiac defects, homeotic anterior transformation, piebaldism, and urogenital anomalies. is a previously unannotated -like paralog with NAT activity that genetically compensates for . Mice deficient for have no apparent phenotype, whereas mice deficient for and display embryonic lethality. The discovery of adds to the currently known machinery involved in amino-terminal acetylation in mice.
Topics: Acetylation; Animals; Female; Male; Mice; Mice, Knockout; N-Terminal Acetyltransferase A; N-Terminal Acetyltransferase E
PubMed: 34355692
DOI: 10.7554/eLife.65952 -
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 Dermato-venereologica Jul 2021The aim of this study was to assess the efficacy of non-cultured autologous epidermal cell grafting resuspended in hyaluronic acid, performed using a ready-to-use kit,... (Randomized Controlled Trial)
Randomized Controlled Trial
Assessment of Non-cultured Autologous Epidermal Cell Grafting Resuspended in Hyaluronic Acid for Repigmenting Vitiligo and Piebaldism Lesions: A Randomized Clinical Trial.
The aim of this study was to assess the efficacy of non-cultured autologous epidermal cell grafting resuspended in hyaluronic acid, performed using a ready-to-use kit, compared with hyaluronic acid alone (neutral comparator) for repigmenting vitiligo and piebaldism lesions at 6 months. Two identified paired lesions per patient were randomized to be treated by either device. Devices with a ready-to-use kit were prepared by separate health professionals, to maintain blinding. A skin biopsy was digested using trypsin, and cells resuspended in hyaluronic acid solution. Among 38 patients screened, 36 (94.7%) patients, corresponding to 72 lesions, were analysed. For difficult-to-treat lesions, defined as those located on the wrist, elbow, and hands (n = 30), no repigmentation ≥ 50% was observed. For all other locations (n = 42), the success rate was significantly higher (p = 0.021) in the ready-to-use kit group (47.6% vs 9.5%) at 6 months and was maintained until 12 months. In conclusion, a single application of non-cultured epidermal cellular grafting using a ready-to-use kit was efficient at 6 months and at 1-year follow-up.
Topics: Epidermal Cells; Humans; Hyaluronic Acid; Piebaldism; Skin Pigmentation; Skin Transplantation; Transplantation, Autologous; Treatment Outcome; Vitiligo
PubMed: 34230975
DOI: 10.2340/00015555-3870 -
Animal Genetics Oct 2021Autochthonous cattle breeds constitute important reservoirs of genetic diversity. Reggiana is an Italian local cattle breed reared in the north of Italy for the...
Exploiting within-breed variability in the autochthonous Reggiana breed identified several candidate genes affecting pigmentation-related traits, stature and udder defects in cattle.
Autochthonous cattle breeds constitute important reservoirs of genetic diversity. Reggiana is an Italian local cattle breed reared in the north of Italy for the production of a mono-breed Parmigiano-Reggiano cheese. Reggiana cattle usually have a classical solid red coat colour and pale muzzle. As part of the strategies designed for the sustainable conservation of this genetic resource, we investigated at the genome-wise level the within-breed detected variability of three pigmentation-related traits (intensity of red coat colour, based on three classes - light/diluted, normal and dark; spotted patterns/piebaldism that sometime emerge in the breed; muzzle colour - pink/pale, grey and black), stature, presence/absence and number of supernumerary teats and teat length. A total of 1776 Reggiana cattle (about two-thirds of the extant breed population) were genotyped with the GeneSeek GGP Bovine 150k SNP array and single-marker and haplotype-based GWASs were carried out. The results indicated that two main groups of genetic factors affect the intensity of red coat colour: darkening genes (including EDN3 and a few other genes) and diluting genes (including PMEL and a few other genes). Muzzle colour was mainly determined by MC1R gene markers. Piebaldism was mainly associated with KIT gene markers. Stature was associated with BTA6 markers upstream of the NCAPG-LCORL genes. Teat defects were associated with TBX3/TBX5, MCC and LGR5 genes. Overall, the identified genomic regions not only can be directly used in selection plans in the Reggiana breed, but also contribute to clarifying the genetic mechanisms involved in determining exterior traits in cattle.
Topics: Animals; Body Size; Breeding; Cattle; Female; Genotype; Haplotypes; Italy; Mammary Glands, Animal; Pigmentation; Polymorphism, Single Nucleotide
PubMed: 34182594
DOI: 10.1111/age.13109 -
BMC Genomics Jun 2021Copper was used for many years in aquaculture operations as an effective algaecide or a parasite treatment of fish. It is an essential nutrient with numerous functions...
BACKGROUND
Copper was used for many years in aquaculture operations as an effective algaecide or a parasite treatment of fish. It is an essential nutrient with numerous functions in organisms, but is toxic at high concentrations. However, the toxicity of copper to fish remains unclear. In this study, we used the piebald naked carp, Gymnocypris eckloni, as a model. RNA-seq data from different tissues, including gills, kidney, and liver, were used to investigate the underlying mechanism of copper toxicology in G. eckloni.
RESULTS
We compared the transcriptomes from different tissues with different time durations of copper ion treatment. After 72 h copper ion treatment, the number of genes with different expression in gills and liver changed dramatically, but not in kidneys. In KEGG functional enrichment, the pattern of differentially expressed genes (DEGs) was also similar in the gills and liver. The most enriched pathway of DEGs was "Ribosome" in both tissues. Furthermore, we analyzed the expression levels of genes involved in oxidative stress response and protein synthesis using qPCR and RNA-seq data. Our results showed that several genes involved in oxidative stress response were up-regulated both in gills and liver. Up-regulation of these genes indicated that copper treatment caused oxidative stress, which is likely to result in ribosome damage. In addition, our results showed that the expression of Eef1b2, a transcription elongation factor, was decreased in the liver under oxidative stress, and the expression of translation initiation factors Eif4ebp1 and eIF2α, and elongation factor eEF2 was up-regulated. These results supported the idea that oxidative stress inhibits protein synthesis in cells.
CONCLUSIONS
Our results indicate that copper exposure caused different responses in different tissues, since the gene expression patterns changed substantially either in the gills or liver, while the effect on the kidney was relatively weak. Furthermore, our results indicated that the expression pattern of the genes involved in the ribosome, which is a complex molecular machine orchestrating protein synthesis in the cell, together with translation initiation factor and elongation factors, were affected by copper exposure both in the gills and liver of piebald naked carp. This result leads us to speculate that the downregulation of global protein synthesis is an acute response strategy of fish to metal-induced oxidative stress. Moreover, we speculate that this strategy not only exists in the selective translation of proteins but also exists in the specific translation of functional proteins in tissues and cells.
Topics: Animals; Carps; Copper; Gene Expression Profiling; Gills; Transcriptome
PubMed: 34090338
DOI: 10.1186/s12864-021-07673-4 -
BMC Pediatrics May 2021Griscelli syndrome type 2 (GS2) is a rare autosomal recessive disease caused by mutations in RAB27A gene. It is primarily characterized by a combination of partial...
BACKGROUND
Griscelli syndrome type 2 (GS2) is a rare autosomal recessive disease caused by mutations in RAB27A gene. It is primarily characterized by a combination of partial albinism, hemophagocytic lymphohistiocytosis (HLH) or other immunodeficiency. However, neurological involvement at onset in GS2 and treatment has rarely been described.
CASE PRESENTATION
We describe a 3-year-old boy with GS2 in an Asian Chinese family. He presented with progressive neurological abnormalities following unremitting fever at onset. He developed HLH during the clinical course. A novel homozygous mutation (c.1 A > G) in RAB27A gene was subsequently identified. He was then treated by HLH-1994 protocol combined with ruxolitinib and experienced a dramatic remission. He subsequently underwent a successful haploidentical hematopoietic stem cell transplantation and stayed at a good condition.
CONCLUSIONS
We reported an atypical form of GS2 manifesting as severe central nervous system involvement at onset and subsequent HLH, which was successfully rescued in time. This case also highlights the need for early consideration of immunologic and genetic evaluation for HLH in unexplained neuroinflammation in the diagnostic work up.
Topics: Child, Preschool; Humans; Lymphohistiocytosis, Hemophagocytic; Male; Piebaldism; Primary Immunodeficiency Diseases; rab27 GTP-Binding Proteins
PubMed: 34058999
DOI: 10.1186/s12887-021-02720-1 -
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