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Iranian Journal of Allergy, Asthma, and... Aug 2022Type 2 Griscelli syndrome (Type2 GS) is a primary inborn error of the immune system, classified in the immune dysregulation group.1,2 There are three different types of...
Type 2 Griscelli syndrome (Type2 GS) is a primary inborn error of the immune system, classified in the immune dysregulation group.1,2 There are three different types of the disease, with different genetic causes responsible for the autosomal recessive inheritance pattern. Although hypopigmentation is common in all variants, neurological involvement or immunodeficiency with varying severity is seen in different types. Molecular motor protein myosin 5 an (MYo5A) [Type1GS], guanosine Triphosphate (GTP) binding protein (RAB27A) [Type2GS], and mutation in human melanophilin (MLPH) [Type 3GS] which is limited to hypopigmentation are reported as the known genetic defects in GS.3 Severe, ineffective, and uncontrolled inflammatory reactions are referred to as the pathogenesis of Hemophagocytic lymphohistiocytosis (HLH). HLH is a life-threatening condition that can be defined as either primary or secondary. Secondary causes happen in the context of autoimmunity, malignancy, spontaneous, or infections.4 Prenatal infections play an important role in causing long-term complications in the fetus. Some of them include toxoplasmosis, rubella, cytomegalovirus, herpes simplex, and other organisms including syphilis, parvovirus, and Varicella zoster, known as TORCH syndrome (5).TORCH has been well described for a long time but there are limited reports of developing HLH in the context of prenatal infections. We described a type 2GS syndrome with neonatal-onset HLH triggered by a prenatal infection.
Topics: Chickenpox; Guanosine Triphosphate; Herpes Zoster; Humans; Hypopigmentation; Infant, Newborn; Lymphohistiocytosis, Hemophagocytic; Myosins; Piebaldism; Primary Immunodeficiency Diseases
PubMed: 36243938
DOI: 10.18502/ijaai.v21i4.10297 -
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 -
Scientific Reports Sep 2022While it is well-established that bone responds dynamically to mechanical loading, the effects of mild traumatic brain injury (mTBI) on cranial bone composition are...
While it is well-established that bone responds dynamically to mechanical loading, the effects of mild traumatic brain injury (mTBI) on cranial bone composition are unclear. We hypothesized that repeated mTBI (rmTBI) would change the microstructure of cranial bones, without gross skull fractures. To address this, young adult female Piebald Viral Glaxo rats received sham, 1×, 2× or 3× closed-head mTBIs delivered at 24 h intervals, using a weight-drop device custom-built for reproducible impact. Skull bones were collected at 2 or 10 weeks after the final injury/sham procedure, imaged by micro computed tomography and analyzed at predetermined regions of interest. In the interparietal bone, proximal to the injury site, modest increases in bone thickness were observed at 2 weeks, particularly following 2× and 3× mTBI. By 10 weeks, 2× mTBI induced a robust increase in the volume and thickness of the interparietal bone, alongside a corresponding decrease in the volume of marrow cavities in the diploë region. In contrast, neither parietal nor frontal skull samples were affected by rmTBI. Our findings demonstrate time- and location-dependent effects of rmTBI on cranial bone structure, highlighting a need to consider microstructural alterations to cranial bone when assessing the consequences of rmTBI.
Topics: Animals; Brain Concussion; Brain Injuries, Traumatic; Disease Models, Animal; Female; Rats; Skull; Time; X-Ray Microtomography
PubMed: 36050485
DOI: 10.1038/s41598-022-18643-5 -
American Journal of Veterinary Research Aug 2022To assess the presence of suspected pigment-associated deafness in North American yaks (Bos grunniens).
OBJECTIVE
To assess the presence of suspected pigment-associated deafness in North American yaks (Bos grunniens).
ANIMALS
12 North American yaks, including 11 with the homozygous piebald Royal pigmentation phenotype and 1 with the heterozygous piebald Trim phenotype.
PROCEDURES
Hearing was assessed using the brainstem auditory evoked response (BAER) on yaks restrained in the head gate of a grooming chute.
RESULTS
Five of the Royal yaks and the Trim yak had hearing in both ears. Six Royal yaks were affected; 3 were deaf in 1 ear and 3 were deaf in both ears.
CLINICAL RELEVANCE
For the first time, probable sensorineural deafness has been confirmed to be present in Royal yaks. The disorder is assumed to be congenital and associated with white pigmentation, based on the pattern of occurrence in other species.
Topics: Animals; Cattle; Cattle Diseases; Deafness; North America; Phenotype; Pigmentation
PubMed: 35914095
DOI: 10.2460/ajvr.22.03.0050 -
Journal of the European Academy of... Sep 2022Pathogenic variants in KITLG, a crucial protein involved in pigmentation and neural crest cell migration, cause non-syndromic hearing loss, Waardenburg syndrome type 2,...
BACKGROUND
Pathogenic variants in KITLG, a crucial protein involved in pigmentation and neural crest cell migration, cause non-syndromic hearing loss, Waardenburg syndrome type 2, familial progressive hyperpigmentation and familial progressive hyper- and hypopigmentation, all of which are inherited in an autosomal dominant manner.
OBJECTIVES
To describe the genotypic and clinical spectrum of biallelic KITLG-variants.
METHODS
We used a genotype-first approach through the GeneMatcher data sharing platform to collect individuals with biallelic KITLG variants and reviewed the literature for overlapping reports.
RESULTS
We describe the first case series with biallelic KITLG variants; we expand the known hypomelanosis spectrum to include a 'sock-and-glove-like', symmetric distribution, progressive repigmentation and generalized hypomelanosis. We speculate that KITLG biallelic loss-of-function variants cause generalized hypomelanosis, whilst variants with residual function lead to a variable auditory-pigmentary disorder mostly reminiscent of Waardenburg syndrome type 2 or piebaldism.
CONCLUSIONS
We provide consolidating evidence that biallelic KITLG variants cause a distinct auditory-pigmentary disorder. We evidence a significant clinical variability, similar to the one previously observed in KIT-related piebaldism.
Topics: Hearing Loss, Sensorineural; Humans; Hyperpigmentation; Hypopigmentation; Piebaldism; Stem Cell Factor; Waardenburg Syndrome
PubMed: 35543077
DOI: 10.1111/jdv.18207 -
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 -
Annals of Laboratory Medicine May 2022
Topics: Humans; Lymphohistiocytosis, Hemophagocytic; Piebaldism; Primary Immunodeficiency Diseases; Republic of Korea
PubMed: 34907113
DOI: 10.3343/alm.2022.42.3.384 -
Genes Sep 2021A 1-month-old, female, smooth-haired miniature Dachshund with dilute color and neurological defects was investigated. The aim of this study was to characterize the...
A 1-month-old, female, smooth-haired miniature Dachshund with dilute color and neurological defects was investigated. The aim of this study was to characterize the clinical signs, histopathological changes and underlying genetic defect. The puppy had visible coat color dilution and was unable to hold its head on its own or to remain in a stable prone position for an extended period. Histopathological examination revealed an accumulation of clumped melanin and deposition of accumulated keratin within the hair follicles, accompanied by dermal pigmentary incontinence. These dermatological changes were compatible with the histopathology described in dogs with an -related dilute coat color. We sequenced the genome of the affected dog and compared the data to 795 control genomes. , coding for myosin VA, was investigated as the top functional candidate gene. This search revealed a private homozygous frameshift variant in , XM_022412522.1:c.4973_4974insA, predicted to truncate 269 amino acids (13.8%) of the wild type myosin VA protein, XP_022268230.1:p.(Asn1658Lysfs*28). The genotypes of the index family showed the expected co-segregation with the phenotype and the mutant allele was absent from 142 additionally genotyped, unrelated Dachshund dogs. loss of function variants cause Griscelli type 1 syndrome in humans, lavender foal in horses and the phenotype of the mouse mutant. Based on the available data, together with current knowledge on other species, we propose the identified frameshift insertion as a candidate causative variant for the observed dermatological and neurological signs in the investigated dog.
Topics: Alleles; Animals; Dog Diseases; Dogs; Frameshift Mutation; Genetic Predisposition to Disease; Genotype; Hair Color; Hearing Loss, Sensorineural; Homozygote; Humans; Myosin Heavy Chains; Myosin Type V; Phenotype; Piebaldism; Pigmentation; Pigmentation Disorders
PubMed: 34680875
DOI: 10.3390/genes12101479 -
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 -
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