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JMIR Dermatology Nov 2023Oculocutaneous albinism is a congenital disorder that causes hypopigmentation of the skin, hair, and eyes due to a lack of melanin. People with albinism are at increased...
BACKGROUND
Oculocutaneous albinism is a congenital disorder that causes hypopigmentation of the skin, hair, and eyes due to a lack of melanin. People with albinism are at increased risk of developing skin complications, such as solar keratosis and skin cancers, leading to higher morbidity. As education is crucial in managing albinism, leveraging information technology, such as WhatsApp, can provide an effective intervention for digital health education.
OBJECTIVE
This study aims to assess the impact of WhatsApp as a tool for providing health education among people with albinism.
METHODS
The design of the study was interventional. The intervention consisted of weekly health education sessions conducted in a WhatsApp group for the duration of 4 weeks. The topics discussed were knowledge of albinism, sun protection practices, the use of sunscreen, and myths about albinism. They were all covered in 4 WhatsApp sessions held in 4 separate days. A web-based questionnaire was filled out before and after the intervention by the participants. Mann-Whitney U test was used to compare the pre- and postknowledge scores. Spearman correlation was used to correlate data.
RESULTS
The mean age of the study participants was 28.28 (SD 11.57) years. The number of participants was 140 in the preintervention period and 66 in the postintervention period. A statistically significant increase in overall knowledge (P=.01), knowledge of sunscreen (P=.01), and knowledge of sun protection (P<.01) was observed following the intervention. Before the intervention, a positive correlation was observed between age (r=0.17; P=.03) and education level (r=0.19; P=.02) with participants' overall knowledge. However, after the intervention, there was no significant correlation between knowledge and age or education level. A percentage increase of 5.23% was observed in the overall knowledge scores following the intervention.
CONCLUSIONS
WhatsApp is an effective tool for educating people with albinism and can act as an alternative to the conventional methods of health education. It shows promising outcomes irrespective of the health literacy level of people with albinism. This educational intervention can positively impact behavior change and translate to consistent sun protection practices. The limitations of this study include the possibility of social desirability bias and data security.
PubMed: 37988154
DOI: 10.2196/49950 -
G3 (Bethesda, Md.) Feb 2024Bird plumage coloration is a complex and multifactorial process that involves both genetic and environmental factors. Diverse pigment groups contribute to plumage...
Bird plumage coloration is a complex and multifactorial process that involves both genetic and environmental factors. Diverse pigment groups contribute to plumage variation in different birds. In parrots, the predominant green color results from the combination of 2 different primary colors: yellow and blue. Psittacofulvin, a pigment uniquely found in parrots, is responsible for the yellow coloration, while blue is suggested to be the result of light scattering by feather nanostructures and melanin granules. So far, genetic control of melanin-mediated blue coloration has been elusive. In this study, we demonstrated that feather from the yellow mutant rose-ringed parakeet displays loss of melanosome granules in spongy layer of feather barb. Using whole genome sequencing, we found that mutation in SLC45A2, an important solute carrier protein in melanin synthetic pathway, is responsible for the sex-linked yellow phenotype in rose-ringed parakeet. Intriguingly, one of the mutations, P53L found in yellow Psittacula krameri is already reported as P58A/S in the human albinism database, known to be associated with human OCA4. We further showed that mutations in SLC45A2 gene affect melanin production also in other members of Psittaculidae family such as alexandrine and plum-headed parakeets. Additionally, we demonstrate that the mutations associated with the sex-linked yellow phenotype, localized within the transmembrane domains of the SLC45A2 protein, affect the protein localization pattern. This is the first evidence of plumage color variation involving SLC45A2 in parrots and confirmation of associated mutations in the transmembrane domains of the protein that affects its localization.
Topics: Humans; Animals; Melanins; Feathers; Mutation; Parrots; Phenotype; Pigmentation; Antigens, Neoplasm; Membrane Transport Proteins
PubMed: 37943814
DOI: 10.1093/g3journal/jkad254 -
Neurology India 2023
Topics: Humans; Primary Immunodeficiency Diseases; Piebaldism; Lymphohistiocytosis, Hemophagocytic; Nervous System Diseases
PubMed: 37929462
DOI: 10.4103/0028-3886.388096 -
Journal of Optometry 2024
Topics: Humans; Albinism; Photosensitivity Disorders
PubMed: 37925940
DOI: 10.1016/j.optom.2023.100503 -
Cureus Oct 2023Hermansky-Pudlak syndrome (HPS) is a group of 10 autosomal recessive inherited diseases. Most patients exhibit albinism with nystagmus, visual acuity loss, and a...
Hermansky-Pudlak syndrome (HPS) is a group of 10 autosomal recessive inherited diseases. Most patients exhibit albinism with nystagmus, visual acuity loss, and a platelet storage pool deficiency with bleeding diathesis. The severity and variety of other clinical features depend on the HPS subtype. We report a 24-year-old male with end-stage renal disease (ESRD) of unknown etiology and a history of oculocutaneous albinism and bleeding diathesis. Two of his siblings also had oculocutaneous albinism. The diagnostic workup for renal impairment was unremarkable. Further genetic testing revealed a homozygous novel nonsense mutation in the gene. Additionally, a heterozygous variant of uncertain significance was identified in the gene. Renal failure is an uncommon clinical feature of HPS. To our knowledge, this is the first case that describes the association of HPS types 5 and 6 with renal failure.
PubMed: 37908700
DOI: 10.7759/cureus.47970 -
International Journal of Molecular... Oct 2023Rice false smut (RFS) caused by (anamorph: ) has become one of the most destructive fungal diseases to decrease the yield and quality of rice grains. An albino strain...
Rice false smut (RFS) caused by (anamorph: ) has become one of the most destructive fungal diseases to decrease the yield and quality of rice grains. An albino strain LN02 was isolated from the white RFS balls collected in the Liaoning Province of China in 2019. The strain LN02 was considered as a natural albino mutant of by analyzing its phenotypes, internal transcribed spacer (ITS) conserved sequence, and biosynthesis gene clusters (BGCs) for secondary metabolites. The total assembled genome of strain LN02 was 38.81 Mb, which was comprised of seven nuclear chromosomes and one mitochondrial genome with an N50 value of 6,326,845 bp and 9339 protein-encoding genes. In addition, the genome of strain LN02 encoded 19 gene clusters for biosynthesis of secondary metabolites mainly including polyketides, terpenoids and non-ribosomal peptides (NRPs). Four sorbicillinoid metabolites were isolated from the cultures of strain LN02. It was found that the polyketide synthase (PKS)-encoding gene for ustilaginoidin biosynthesis in strain LN02 was inactivated due to the deletion of four bases in the promoter sequence of . The normal complementary mutant of strain LN02 could restore the ability to synthesize ustilaginoidins. It demonstrated that deficiency of ustilaginoidin biosynthesis is the cause of albinism for RFS albino strain LN02, and should be a non-melanin-producing fungus. This study further confirmed strain LN02 as a white phenotype mutant of . The albino strain LN02 will have a great potential in the development and application of secondary metabolites. The physiological and ecological functions of ustilaginoidins in RFS fungus are needed for further investigation.
Topics: Oryza; Hypocreales; Multigene Family; Genetic Variation; Plant Diseases
PubMed: 37894876
DOI: 10.3390/ijms242015196 -
Biomedicine & Pharmacotherapy =... Dec 2023Hermansky-Pudlak syndrome (HPS) is a rare autosomal recessive disorder that affects lysosome-related organelles, often leading to fatal pulmonary fibrosis (PF). The...
In vitro and in vivo pharmacokinetic characterization, chiral conversion and PBPK scaling towards human PK simulation of S-MRI-1867, a drug candidate for Hermansky-Pudlak syndrome pulmonary fibrosis.
Hermansky-Pudlak syndrome (HPS) is a rare autosomal recessive disorder that affects lysosome-related organelles, often leading to fatal pulmonary fibrosis (PF). The search for a treatment for HPS pulmonary fibrosis (HPSPF) is ongoing. S-MRI-1867, a dual cannabinoid receptor 1 (CBR)/inducible nitric oxide synthase (iNOS) inhibitor, has shown great promise for the treatment of several fibrotic diseases, including HPSPF. In this study, we investigated the in vitro ADME characteristics of S-MRI-1867, as well as its pharmacokinetic (PK) properties in mice, rats, dogs, and monkeys. S-MRI-1867 showed low aqueous solubility (< 1 µg/mL), high plasma protein binding (>99%), and moderate to high metabolic stability. In its preclinical PK studies, S-MRI-1867 exhibited moderate to low plasma clearance (CL) and high steady-state volume of distribution (Vd) across all species. Despite the low solubility and P-gp efflux, S-MRI-1867 showed great permeability and metabolic stability leading to a moderate bioavailability (21-60%) across mouse, rat, dog, and monkey. Since the R form of MRI-1867 is CBR-inactive, we investigated the potential conversion of S-MRI-1867 to R-MRI-1867 in mice and found that the chiral conversion was negligible. Furthermore, we developed and validated a PBPK model that adequately fits the PK profiles of S-MRI-1867 in mice, rats, dogs, and monkeys using various dosing regimens. We employed this PBPK model to simulate the human PK profiles of S-MRI-1867, enabling us to inform human dose selection and support the advancement of this promising drug candidate in the treatment of HPSPF.
Topics: Humans; Rats; Mice; Animals; Dogs; Pulmonary Fibrosis; Hermanski-Pudlak Syndrome; Research Design
PubMed: 37890204
DOI: 10.1016/j.biopha.2023.115178 -
Molecular Genetics & Genomic Medicine Jan 2024Oculocutaneous albinism (OCA) is a group of rare autosomal recessive disorders characterized by clinical genetic heterogeneity. OCA type II (OMIM: 203200) is the most...
BACKGROUND
Oculocutaneous albinism (OCA) is a group of rare autosomal recessive disorders characterized by clinical genetic heterogeneity. OCA type II (OMIM: 203200) is the most common subtype among African and African Americans, primarily caused by pathogenic variants in the OCA2 (HGNC ID: 8101) gene. In this study, we presented a Chinese family with OCA and reported two novel variants in the OCA2 gene.
METHODS
Whole-exome sequencing (WES) was performed to identify pathogenic variants in the proband. The candidate variants were subsequently validated using Sanger sequencing and QPCR assay. Additionally, bioinformatics analyses were employed to predict the deleteriousness and conservation of the identified mutations.
RESULTS
In the 16-year-old male proband, two novel compound heterozygous OCA2 variants, NM_000275.3: c.1640T>G (NP_000266.2: p.L547R) and an exons 10-19 deletion variant, were identified. Meanwhile, a reported heterozygous variant c.1441G>A/p.A481T (NM_000275.3, NP_000266.2) in the OCA2 gene was also found in the proband. Sanger sequencing confirmed that the two variants c.1441G>A/p.A481T and c.1640T>G/p.L547R were inherited from his father. Moreover, qPCR assay revealed that the exons 10-19 deletion was inherited from the mother, his sister also carried this variant. Fortunately, the variant was not detected in the amniotic fluid of the proband's sister. Multiple online bioinformatics tools predicted the variant c.1640T>G to be damaging, leading to the replacement of a highly conserved leucine with an arginine. The gross exon 10-19 deletion in the OCA2 gene resulted in a truncated, non-functional protein losing the 3-9 transmembrane α-helices domains. According to the American College of Medical Genetics and Genomics classification, these three variants in the OCA2 gene were evaluated as likely pathogenic.
CONCLUSION
This study has identified two novel compound variants in the OCA2 gene and a previously reported variant in a Chinese family with OCA. By expanding the mutation spectrum of the OCA2 gene, our findings contribute to a better understanding of the genetic basis of OCA.
Topics: Male; Humans; Adolescent; Membrane Transport Proteins; Albinism, Oculocutaneous; Mutation; China
PubMed: 37882226
DOI: 10.1002/mgg3.2297 -
Investigative Ophthalmology & Visual... Oct 2023We aimed to generate and phenotype a mouse model of foveal hypoplasia, optic nerve decussation defects, and anterior segment dysgenesis (FHONDA), a rare disease...
PURPOSE
We aimed to generate and phenotype a mouse model of foveal hypoplasia, optic nerve decussation defects, and anterior segment dysgenesis (FHONDA), a rare disease associated with mutations in Slc38a8 that causes severe visual alterations similar to albinism without affecting pigmentation.
METHODS
The FHONDA mouse model was generated with clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 technology using an RNA guide targeting the Scl38a8 murine locus. The resulting mice were backcrossed to C57BL/6J. Melanin content was measured using spectrophotometry. Retinal cell architecture was analyzed through light and electron microscopy. Retinal projections to the brain were evaluated with anterograde labelling in embryos and adults. Visual function was assessed by electroretinography (ERG) and the optomotor test (OT).
RESULTS
From numerous Slc38a8 mouse mutant alleles generated, we selected one that encodes a truncated protein (p.196Pro*, equivalent to p.199Pro* in the human protein) closely resembling a mutant allele described in patients (p.200Gln*). Slc38a8 mutant mice exhibit wild-type eye and coat pigmentation with comparable melanin content. Subcellular abnormalities were observed in retinal pigment epithelium cells of Slc38a8 mutant mice. Anterograde labeling experiments of retinal projections in embryos and adults showed a reduction of ipsilateral fibers. Functional visual analyses revealed a decreased ERG response in scotopic conditions and a reduction of visual acuity in mutant mice measured by OT.
CONCLUSIONS
Slc38a8 mutant mice recapitulate the phenotype of patients with FHONDA concerning their normal pigmentation and their abnormal visual system, in the latter being a hallmark of all types of albinism. These mice will be helpful in better understanding the pathophysiology of this genetic condition.
Topics: Adult; Humans; Mice; Animals; Melanins; Mice, Inbred C57BL; Albinism; Eye Abnormalities; Pigmentation; Amino Acid Transport Systems, Neutral
PubMed: 37862028
DOI: 10.1167/iovs.64.13.32 -
JAAD Case Reports Nov 2023
PubMed: 37842156
DOI: 10.1016/j.jdcr.2023.08.023