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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 -
Neurology India 2023
Topics: Humans; Primary Immunodeficiency Diseases; Piebaldism; Lymphohistiocytosis, Hemophagocytic; Nervous System Diseases
PubMed: 37929462
DOI: 10.4103/0028-3886.388096 -
BioRxiv : the Preprint Server For... Jul 2023Variation in pigment patterns within and among vertebrate species reflects underlying changes in cell migration and function that can impact health, reproductive...
Variation in pigment patterns within and among vertebrate species reflects underlying changes in cell migration and function that can impact health, reproductive success, and survival. The domestic pigeon () is an exceptional model for understanding the genetic changes that give rise to diverse pigment patterns, as selective breeding has given rise to hundreds of breeds with extensive variation in plumage color and pattern. Here, we map the genetic architecture of a suite of pigmentation phenotypes known as piebalding. Piebalding is characterized by patches of pigmented and non-pigmented feathers, and these plumage patterns are often breed-specific and stable across generations. Using a combination of quantitative trait locus mapping in F laboratory crosses and genome-wide association analysis, we identify a locus associated with piebalding across many pigeon breeds. This shared locus harbors a candidate gene, that is a known regulator of pigment cell migration, proliferation, and survival. We discover multiple distinct haplotypes at the locus in piebald pigeons, which include a mix of protein-coding, noncoding, and structural variants that are associated with depigmentation in specific plumage regions. These results identify a role for in pigment patterning in the domestic pigeon, and highlight how repeated selection at a single locus can generate a diverse array of stable and heritable pigment patterns.
PubMed: 37546953
DOI: 10.1101/2023.07.26.550625 -
Journal of the European Academy of... Apr 2023
Topics: Humans; Piebaldism; Vitiligo; Hypopigmentation; Skin Transplantation; Burns
PubMed: 36545938
DOI: 10.1111/jdv.18829 -
PLoS Genetics Oct 2023Variation in pigment patterns within and among vertebrate species reflects underlying changes in cell migration and function that can impact health, reproductive...
Variation in pigment patterns within and among vertebrate species reflects underlying changes in cell migration and function that can impact health, reproductive success, and survival. The domestic pigeon (Columba livia) is an exceptional model for understanding the genetic changes that give rise to diverse pigment patterns, as selective breeding has given rise to hundreds of breeds with extensive variation in plumage color and pattern. Here, we map the genetic architecture of a suite of pigmentation phenotypes known as piebalding. Piebalding is characterized by patches of pigmented and non-pigmented feathers, and these plumage patterns are often breed-specific and stable across generations. Using a combination of quantitative trait locus mapping in F2 laboratory crosses and genome-wide association analysis, we identify a locus associated with piebalding across many pigeon breeds. This shared locus harbors a candidate gene, EDNRB2, that is a known regulator of pigment cell migration, proliferation, and survival. We discover multiple distinct haplotypes at the EDNRB2 locus in piebald pigeons, which include a mix of protein-coding, noncoding, and structural variants that are associated with depigmentation in specific plumage regions. These results identify a role for EDNRB2 in pigment patterning in the domestic pigeon, and highlight how repeated selection at a single locus can generate a diverse array of stable and heritable pigment patterns.
Topics: Animals; Columbidae; Genome-Wide Association Study; Feathers; Phenotype; Pigmentation
PubMed: 37862332
DOI: 10.1371/journal.pgen.1010880 -
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 -
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 -
Diseases of Aquatic Organisms Aug 2019Atypical pigmentation, which is rarely observed in the wild, may influence social interactions between animals and can be detrimental for survival. Hypopigmentation,...
Atypical pigmentation, which is rarely observed in the wild, may influence social interactions between animals and can be detrimental for survival. Hypopigmentation, which is the lack of pigment in a part or on the entire body, is a type of atypical pigmentation pattern that can be either acquired (e.g. vitiligo) or congenital resulting from the inheritance of mutations in pigment-related genes (e.g. albinism, leucism and piebaldism). This study documents atypical pigmentation in a fin whale Balaenoptera physalus off the northwestern coast of the Iberian Peninsula (Atlantic Ocean). Photographic and video data collected between 2016 and 2017 on 30 individual fin whales were examined. One fully-grown fin whale exhibited hypopigmentation. Several white patches of different shapes and sizes were present across the body of the fin whale including on the head, body, dorsal fin, flippers, and flukes. The position, shape, and lack of inflammation of the white patches on the whale observed, along with its body length and condition, might indicate that the depigmentation pattern is due to vitiligo. To our knowledge, this is the first case of atypical pigmentation pattern in fin whales described with photographs and video records. As these observations are rare, especially in highly migratory, long-lived, marine mammal species, this study provides valuable information to better understand the occurrence of this phenomenon. Further studies are needed to determine the ecological and physiological implications of atypical colourations, which might have a significant influence on the animal's survival.
Topics: Animals; Atlantic Ocean; Fin Whale; Pigmentation; Whales
PubMed: 31392964
DOI: 10.3354/dao03385 -
Japanese Journal of Radiology Mar 2023Solitary and solid pulmonary tuberculosis (PTB) and non-small cell lung cancer (NSCLC) can present overlapping imaging features, causing diagnostic dilemmas. Hence, this...
OBJECTIVE
Solitary and solid pulmonary tuberculosis (PTB) and non-small cell lung cancer (NSCLC) can present overlapping imaging features, causing diagnostic dilemmas. Hence, this study aimed to identify positron emission tomography (PET) morphological features derived from fluorine-18-fluorodeoxyglucose positron emission tomography/computed tomography (F-FDG PET/CT) images for a better differential diagnosis.
METHODS
Clinical records and F-FDG PET/CT images of 175 patients confirmed with PTB and 311 patients with NSCLC were retrospectively reviewed. Parameters including patient demographics, PET-derived morphological features and metabolic parameters, and CT-derived morphological features were investigated. Logistic regression analysis was performed to assess the independent predictive factors associated with PTB.
RESULTS
PTB presented with more heterogeneous glucometabolism than NSCLC in PET imaging (50% vs 17%, P < 0.05), especially in lesions with a maximum diameter < 30 mm (39% vs. 5%, P < 0.05). NSCLC usually showed centric hypometabolism, whereas PTB more frequently presented with an eccentric metabolic pattern, mainly including piebald, half-side, lesser curvature, and greater curvature shapes. Multivariate logistic regression identified that glucometabolic heterogeneity, eccentric hypometabolism, smaller lesion size, calcification, satellite lesions, and higher CT value of the hypometabolic area were independently diagnostic factors for PTB.
CONCLUSIONS
Morphological features derived from F-FDG PET images helped distinguish solitary and solid PTB from NSCLC.
Topics: Humans; Carcinoma, Non-Small-Cell Lung; Positron Emission Tomography Computed Tomography; Fluorodeoxyglucose F18; Lung Neoplasms; Retrospective Studies; Radiopharmaceuticals; Positron-Emission Tomography; Tuberculosis, Pulmonary
PubMed: 36227458
DOI: 10.1007/s11604-022-01351-5 -
PloS One 2020The births of domestic dogs with pigment deletion and associated congenital hearing and/or vision impairments are increasing, as a result of mutations of certain genes...
Are dogs with congenital hearing and/or vision impairments so different from sensory normal dogs? A survey of demographics, morphology, health, behaviour, communication, and activities.
The births of domestic dogs with pigment deletion and associated congenital hearing and/or vision impairments are increasing, as a result of mutations of certain genes expressing popular coat colour patterns (Merle, piebald, Irish spotting). The future of these dogs is often pessimistic (early euthanasia or placement in rescues/fosters, lack of interactions and activities for adults). These pessimistic scenarios result from popular assumptions predicting that dogs with congenital hearing/vision impairments exhibit severe Merle-related health troubles (cardiac, skeletal, neurological), impairment-related behavioural troubles (aggressiveness, anxiety), and poor capacities to communicate, to be trained, and to be engaged in leisure or work activities. However, there is no direct scientific testing, and hence no evidence or refutation, of these assumptions. We therefore addressed an online questionnaire to owners of 223 congenitally sensory impaired (23 vision impaired, 63 hearing impaired, 137 hearing and vision impaired) and 217 sensory normal dogs from various countries. The sensory normal cohort was matched in age, lifetime with owner, breed and sex with the sensory impaired cohort, and was used as a baseline. The questionnaire assessed demographics, morphology, sensory impairments, health and behavioural troubles, activities, and dog-owner communication. Most hearing and/or vision impaired dogs exhibited abnormal pigment deletion in their coat and irises. Vision impaired dogs additionally exhibited ophthalmic abnormalities typically related to Merle. The results are opposed to all above-listed assumptions, except for neurological troubles, which were more frequently reported in sensory impaired dogs. However, we suggest that this finding could be partially accounted for by a lack of diagnosis of breed-related drug sensitivity and impairment-related compulsive behaviours. Results about communication and activities are particularly optimistic. The need for future studies of numerous dogs from various breeds tested for Merle, piebald and medical-drug-resistance genes, and the beneficial effects that present and future research may have on the future of sensory impaired dogs, are discussed.
Topics: Animals; Behavior, Animal; Blindness; Breeding; Communication; Dog Diseases; Dogs; Female; Hearing Loss; Humans; Male; Pets; Pigmentation; Surveys and Questionnaires
PubMed: 32886662
DOI: 10.1371/journal.pone.0230651