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International Journal of Molecular... Feb 2023Adolescence is a critical period of postnatal development characterized by social, emotional, and cognitive changes. These changes are increasingly understood to depend...
Adolescence is a critical period of postnatal development characterized by social, emotional, and cognitive changes. These changes are increasingly understood to depend on white matter development. White matter is highly vulnerable to the effects of injury, including secondary degeneration in regions adjacent to the primary injury site which alters the myelin ultrastructure. However, the impact of such alterations on adolescent white matter maturation is yet to be investigated. To address this, female piebald-virol-glaxo rats underwent partial transection of the optic nerve during early adolescence (postnatal day (PND) 56) with tissue collection two weeks (PND 70) or three months later (PND 140). Axons and myelin in the transmission electron micrographs of tissue adjacent to the injury were classified and measured based on the appearance of the myelin laminae. Injury in adolescence impaired the myelin structure in adulthood, resulting in a lower percentage of axons with compact myelin and a higher percentage of axons with severe myelin decompaction. Myelin thickness did not increase as expected into adulthood after injury and the relationship between the axon diameter and myelin thickness in adulthood was altered. Notably, dysmyelination was not observed 2 weeks postinjury. In conclusion, injury in adolescence altered the developmental trajectory, resulting in impaired myelin maturation when assessed at the ultrastructural level in adulthood.
Topics: Female; Animals; Rats; Myelin Sheath; Axons; Optic Nerve; Optic Nerve Injuries; Demyelinating Diseases
PubMed: 36834755
DOI: 10.3390/ijms24043343 -
Current Biology : CB Feb 2023Reptiles display great diversity in color and pattern, yet much of what we know about vertebrate coloration comes from classic model species such as the mouse and...
Reptiles display great diversity in color and pattern, yet much of what we know about vertebrate coloration comes from classic model species such as the mouse and zebrafish. Captive-bred ball pythons (Python regius) exhibit a remarkable degree of color and pattern variation. Despite the wide range of Mendelian color phenotypes available in the pet trade, ball pythons remain an overlooked species in pigmentation research. Here, we investigate the genetic basis of the recessive piebald phenotype, a pattern defect characterized by patches of unpigmented skin (leucoderma). We performed whole-genome sequencing and used a case-control approach to discover a nonsense mutation in the gene encoding the transcription factor tfec, implicating this gene in the leucodermic patches in ball pythons. We functionally validated tfec in a lizard model (Anolis sagrei) using the gene editing CRISPR/Cas9 system and TEM imaging of skin. Our findings show that reading frame mutations in tfec affect coloration and lead to a loss of iridophores in Anolis, indicating that tfec is required for chromatophore development. This study highlights the value of captive-bred ball pythons as a model species for accelerating discoveries on the genetic basis of vertebrate coloration.
Topics: Animals; Mice; Piebaldism; Zebrafish; Chromatophores; Lizards; Pigmentation; Zebrafish Proteins; Basic Helix-Loop-Helix Leucine Zipper Transcription Factors
PubMed: 36702128
DOI: 10.1016/j.cub.2023.01.004 -
Molecular Genetics and Genomics : MGG Mar 2023Griscelli syndrome type 1 (GS1) is a rare inherited autosomal recessive disease caused by a deleterious variant in the MYO5A gene and characterized by general... (Review)
Review
Griscelli syndrome type 1 (GS1) is a rare inherited autosomal recessive disease caused by a deleterious variant in the MYO5A gene and characterized by general hypopigmentation, neurological symptoms, motor disability, hypotonia, and vision abnormality. Only nine pathogenic variants in the MYO5A gene have been confirmed in association with the GS1. All of the reported pathogenic variants are truncating. Herein, two siblings from a consanguineous Iranian family with abnormal pigmentation and neurological symptoms were referred for genetic counseling. Whole-exome sequencing (WES) revealed a novel homozygous truncating variant c.1633_1634delAA (p.Asn545Glnfs*10) in the MYO5A gene, which was completely co-segregated with the phenotype in all affected and unaffected family members. Computational analysis and protein modeling demonstrated the deleterious effects of this variant on the structure and function of the protein. The variant, according to ACMG guidelines, was classified as pathogenic. Besides the novelty of the identified variant, our patients manifested more severe clinical symptoms and presented distal hyperlaxity in all four limbs, which was a new finding. In conclusion, we expanded the mutational and phenotypic spectrum of the GS1. Moreover, by studying clinical manifestations in all molecularly confirmed reported cases, provided a comprehensive overview of clinical presentation, and attempted to find a genotype-phenotype correlation.
Topics: Humans; Iran; Disabled Persons; Motor Disorders; Piebaldism; Mutation; Pedigree
PubMed: 36651988
DOI: 10.1007/s00438-022-01971-6 -
Frontiers in Pediatrics 2022We report the case of a girl aged 2 years and 10 months who had fever for 2 days, vomiting, poor mental status for 1 day, and one episode of convulsions.
CASE PRESENTATION
We report the case of a girl aged 2 years and 10 months who had fever for 2 days, vomiting, poor mental status for 1 day, and one episode of convulsions.
SYMPTOMS AND SIGNS
The patient experienced a rapid onset of symptoms with fever, vomiting, and convulsions. Upon physical examination on admission, she presented with the following: temperature 38.6°C; pulse 185 beats/min; respiration 49 beats/min; blood pressure 89/51 mmHg; drowsiness; piebald skin all over her body; rice-grain-sized pustular rashes scattered on the front chest and both lower limbs, protruding from the surface of the skin; bilateral pupils that were equal in size and a circle with a diameter of about 3.0 mm, and slow light reflex; cyanotic lips; shortness of breath; positive for the three-concave sign; a small amount of phlegm that could be heard in both lungs; capillary refill time of 5 s; cold extremities; and a positive Babinski sign.
DIAGNOSTIC METHOD
A chest computed tomography scan showed multiple nodular and flake-like high-density shadows of varying sizes in each lobe in bilateral lungs, and a cavity with blurred edges could be seen in some nodules. A cranial magnetic resonance imaging examination demonstrated that the hyperintensity of diffusion-weighted imaging could be observed on the left cerebellar hemisphere and left parietal blade. Blood cultures, sputum, cerebrospinal fluid, and bronchoalveolar lavage fluid (BALF) by fiberoptic bronchoscopy all indicated the growth of methicillin-resistant (MRSA).
TREATMENT METHODS
After admission, the child was given meropenem combined with vancomycin, cefoperazone sulbactam combined with rifamycin, linezolid (oral) for anti-infection successively, and other adjuvant therapies.
CLINICAL OUTCOMES
The patient recovered clinically and was discharged from our hospital.
RECOMMENDED READERS
Neurology; Respiratory Medicine; Infectious Diseases Department.
PubMed: 36568437
DOI: 10.3389/fped.2022.1045774 -
Genes Nov 2022Albinism is a genetic disorder, present worldwide, caused by mutations in genes affecting melanin production or transport in the skin, hair and eyes. To date, mutations...
Albinism is a genetic disorder, present worldwide, caused by mutations in genes affecting melanin production or transport in the skin, hair and eyes. To date, mutations in at least 20 different genes have been identified. Oculo-cutaneous Albinism type IV (OCA4) is the most frequent form in Asia but has been reported in all populations, including Europeans. Little is known about the genotype-phenotype correlation. We identified two main phenotypes via the analysis of 30 OCA4 patients with a molecularly proven diagnosis. The first, found in 20 patients, is clinically indistinguishable from the classical OCA1 phenotype. The genotype-to-phenotype correlation suggests that this phenotype is associated with homozygous or compound heterozygous nonsense or deletion variants with frameshift leading to translation interruption in the gene. The second phenotype, found in 10 patients, is characterized by very mild hypopigmentation of the hair (light brown or even dark hair) and skin that is similar to the general population. In this group, visual acuity is variable, but it can be subnormal, foveal hypoplasia can be low grade or even normal, and nystagmus may be lacking. These mild to moderate phenotypes are associated with at least one missense mutation in .
Topics: Humans; Piebaldism; Mutation; Mutation, Missense; Phenotype; Genotype
PubMed: 36553465
DOI: 10.3390/genes13122198 -
Journal of the European Academy of... Apr 2023
Topics: Humans; Piebaldism; Vitiligo; Hypopigmentation; Skin Transplantation; Burns
PubMed: 36545938
DOI: 10.1111/jdv.18829 -
Indian Journal of Pediatrics Feb 2023
Topics: Humans; Microscopy; Piebaldism; Pigmentation Disorders; Hair; Immunologic Deficiency Syndromes
PubMed: 36512299
DOI: 10.1007/s12098-022-04422-7 -
Frontiers in Medicine 2022Piebaldism is a rare autosomal dominant disease, and roughly 75% patients had gene mutations. Up to date, approximately 90 mutations causing piebaldism were reported.
BACKGROUND
Piebaldism is a rare autosomal dominant disease, and roughly 75% patients had gene mutations. Up to date, approximately 90 mutations causing piebaldism were reported.
METHODS
To identify gene mutations in three pediatric piebaldism patients from different families and explore the genotype-phenotype correlation, peripheral blood DNA were collected from probands and their parents. Whole-exome sequencing was performed to detect potential disease-causing variants in the three probands. Putative variants were validated by Sanger sequencing.
RESULTS
Heterozygous variants of c.2469_2484del (p.Tyr823*), c.1994G > C (p.Pro665Leu), and c.1982_1983insCAT (p.662_663insIle) in gene were detected in three probands. These variants were all novel and classified as pathogenic/likely pathogenic variants according to the interpretation guidelines of American College of Medical Genetics and Genomics and the Association for Molecular Pathology. The probands carrying variants located in tyrosine kinase domain exhibited a more severe phenotype.
CONCLUSION
The piebaldism in three families was caused by novel heterozygous variants. The severity of phenotypes is related with the types and locations of different mutations. Our results further provided evidence for genetic counseling for the three families.
PubMed: 36438053
DOI: 10.3389/fmed.2022.1040747 -
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 -
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