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Investigative Ophthalmology & Visual... Jul 2023The aim of this systematic review was to investigate the available data on the epidemiology of oculocutaneous albinism (OCA) around the world, and to determine whether a...
PURPOSE
The aim of this systematic review was to investigate the available data on the epidemiology of oculocutaneous albinism (OCA) around the world, and to determine whether a generalizable, worldwide prevalence figure could be proposed.
METHODS
Extensive literature search strategies were conducted, interrogating PubMed, Scopus, and Web of Science, to locate relevant literature. Ultimately 34 studies reporting original data were included for analysis.
RESULTS
Findings showed that most data were outdated, and only 6 of 34 articles (18%) were published after 2010. There were few good studies with sound methodology and large, clearly defined population samples. Only a small proportion of countries worldwide (26/193 [13%]) have produced prevalence figures for OCA. By continent, African studies were disproportionately represented (15/34 [44%]). The highest prevalence rates (range, 1 in 22 to 1 in 1300; mean, 1 in 464) were reported in population isolates. The mean prevalence from four African countries was 1 in 4264 (range, 1 in 1755 to 1 in 7900). Prevalence for three countries in Europe (mean, 1 in 12,000; range, 1 in 10,000 to 1 in 15,000) may be underestimated, as the phenotype, in fair-skinned populations, may be missed or misdiagnosed as ocular albinism or isolated visual impairment. Population rates may vary depending on local cultural factors (e.g., consanguineous matings) and may change over time.
CONCLUSIONS
The prevalence of OCA varies widely between continents and population groups, and it is often influenced by local factors. It was not possible, therefore, to determine a single, generalizable worldwide prevalence rate for OCA, although continental rates for Africa and Europe are useful.
Topics: Humans; Mutation; Prevalence; Albinism, Oculocutaneous; Phenotype; Albinism, Ocular
PubMed: 37440261
DOI: 10.1167/iovs.64.10.14 -
Bioscience Reports Jul 2023Recent innovations in computational structural biology have opened an opportunity to revise our current understanding of the structure and function of clinically...
Recent innovations in computational structural biology have opened an opportunity to revise our current understanding of the structure and function of clinically important proteins. This study centres on human Oca2 which is located on mature melanosomal membranes. Mutations of Oca2 can result in a form of oculocutanous albinism, which is the most prevalent and visually identifiable form of albinism. Sequence analysis predicts Oca2 to be a member of the SLC13 transporter family, but it has not been classified into any existing SLC families. The modelling of Oca2 with AlphaFold2 and other advanced methods show that, like SLC13 members, it consists of a scaffold and transport domain and displays a pseudo inverted repeat topology that includes re-entrant loops. This finding contradicts the prevailing consensus view of its topology. In addition to the scaffold and transport domains, the presence of a cryptic GOLD domain is revealed that is likely responsible for its trafficking from the endoplasmic reticulum to the Golgi prior to localisation at the melanosomes. The GOLD domain harbours some known glycosylation sites. Analysis of the putative ligand binding site of the model shows the presence of highly conserved key asparagine residues that suggest Oca2 may be a Na+/dicarboxylate symporter. Known critical pathogenic mutations map to structural features present in the repeat regions that form the transport domain. Exploiting the AlphaFold2 multimeric modelling protocol in combination with conventional homology modelling allowed the building of plausible homodimers in both inward- and outward-facing conformations, supporting an elevator-type transport mechanism.
Topics: Humans; Membrane Transport Proteins; Albinism, Oculocutaneous; Mutation
PubMed: 37431738
DOI: 10.1042/BSR20230060 -
Alternative Therapies in Health and... Oct 2023This study aims to investigate the main types of oculocutaneous albinism (OCA) and the distribution characteristics of mutations in the Chinese population. Additionally,...
OBJECTIVE
This study aims to investigate the main types of oculocutaneous albinism (OCA) and the distribution characteristics of mutations in the Chinese population. Additionally, genetic diagnosis and prenatal diagnosis were conducted for Chinese OCA families.
METHODS
A total of 116 blood DNA samples were collected from 40 unrelated families with suspected albinism. OCA gene testing and mutation screening were performed to identify mutated genes and genotypes. The prenatal genetic diagnosis was conducted on 20 fetal DNA samples (17 amniotic fluid DNA samples, 2 villus DNA samples, and 1 umbilical cord blood DNA sample). Follow-up was conducted on the born fetuses, and the feasibility and accuracy of prenatal genetic diagnosis were assessed based on the clinical phenotype of the fetuses.
RESULTS
Analysis of 40 pedigrees led to a molecular diagnosis for the patients or their parents: 24 (60%) had OCA1, 12 (30%) had OCA2, 1 (2.5%) had OCA3, and 2 (5%) had OCA4. Furthermore, 2.5% of the patients harbored only one heterozygous mutation in OCA2. The most common form of albinism observed was OCA1, followed by OCA2, OCA4, and OCA3. Prenatal diagnosis was performed on 20 fetuses, and the clinical phenotype of the fetuses aligned with the predictions of prenatal genetic diagnosis after follow-up.
CONCLUSIONS
The results of gene mutation analysis in 40 families with oculocutaneous albinism indicate that OCA1 is the predominant type of albinism in the Chinese population, with all four types of OCA identified. Further research is needed to expand the understanding of pathogenic mutations associated with different types of OCA. Prenatal genetic testing, based on determining the albinism type and genotype of the proband and their parents, proves to be the most accurate and least traumatic method in eugenics. This study provides valuable insights into identifying novel therapeutic targets.
Topics: Pregnancy; Female; Humans; East Asian People; Mutation; Albinism, Oculocutaneous; Phenotype; Membrane Transport Proteins; Membrane Glycoproteins; Oxidoreductases; Antigens, Neoplasm
PubMed: 37471664
DOI: No ID Found -
Hematology Reports Jun 2024Hypopigmentation disorders pose significant diagnostic challenges in dermatology, sometimes reflecting underlying hematological conditions. This review explores the... (Review)
Review
Hypopigmentation disorders pose significant diagnostic challenges in dermatology, sometimes reflecting underlying hematological conditions. This review explores the clinical presentations related to hypopigmentation in hematological disorders, focusing on vitiligo, morphea, and syndromic albinism. Vitiligo, an autoimmune disorder targeting melanocytes, involves interactions between genetic polymorphisms and immune responses, particularly regarding CD8+ T cells and IFN-γ. Drug-induced vitiligo, notably by immune checkpoint inhibitors and small-molecule targeted anticancer therapies, underscores the importance of immune dysregulation. Morphea, an inflammatory skin disorder, may signal hematological involvement, as seen in deep morphea and post-radiotherapy lesions. Syndromic albinism, linked to various genetic mutations affecting melanin production, often presents with hematologic abnormalities. Treatment approaches focus on targeting the immune pathways specific to the condition, and when that is not possible, managing symptoms. Understanding these dermatological manifestations is crucial for the timely diagnosis and management of hematological disorders.
PubMed: 38921184
DOI: 10.3390/hematolrep16020036 -
Investigative Ophthalmology & Visual... Apr 2024Our primary aim was to compare adult full-field ERG (ffERG) responses in albinism, idiopathic infantile nystagmus (IIN), and controls. A secondary aim was to investigate...
PURPOSE
Our primary aim was to compare adult full-field ERG (ffERG) responses in albinism, idiopathic infantile nystagmus (IIN), and controls. A secondary aim was to investigate the effect of within-subject changes in nystagmus eye movements on ffERG responses.
METHODS
Dilated Ganzfeld flash ffERG responses were recorded using DTL electrodes under conditions of dark (standard and dim flash) and light adaptation in 68 participants with albinism, 43 with IIN, and 24 controls. For the primary aim, the effect of group and age on ffERG responses was investigated. For the secondary aim, null region characteristics were determined using eye movements recorded prior to ffERG recordings. ffERG responses were recorded near and away from the null regions of 18 participants also measuring the success rate of recordings.
RESULTS
For the primary aim, age-adjusted photopic a- and b-wave amplitudes were consistently smaller in IIN compared with controls (P < 0.0001), with responses in both groups decreasing with age. In contrast, photopic a-wave amplitudes increased with age in albinism (P = 0.0035). For the secondary aim, more intense nystagmus significantly reduced the success rate of measurable responses. Within-subject changes in nystagmus intensity generated small, borderline significant differences in photopic b-wave peak times and a-and b-wave amplitudes under scotopic conditions with standard flash.
CONCLUSIONS
Age-adjusted photopic ffERG responses are significantly reduced in IIN adding to the growing body of evidence of retinal abnormalities in IIN. Differences between photopic responses in albinism and controls depend on age. Success at obtaining ffERG responses could be improved by recording responses at the null region.
Topics: Adult; Humans; Nystagmus, Congenital; Nystagmus, Pathologic; Eye Movements; Albinism; Genetic Diseases, X-Linked
PubMed: 38573619
DOI: 10.1167/iovs.65.4.11 -
American Journal of Ophthalmology Case... Jun 2024To report a case of unsuccessful transscleral cyclophotocoagulation in a patient with OCA1A tyrosinase-negative oculocutaneous albinism.
PURPOSE
To report a case of unsuccessful transscleral cyclophotocoagulation in a patient with OCA1A tyrosinase-negative oculocutaneous albinism.
OBSERVATIONS
A 35-year-old Asian female with molecularly diagnosed OCA1A (tyrosinase-negative) oculocutaneous albinism and unilateral severe mixed mechanism glaucoma underwent transscleral cyclophotocoagulation on two separate occasions to treat elevated intraocular pressure. The intraocular pressure remained markedly elevated approximately 1 month following two separate treatments of transscleral cyclophotocoagulation while using high energy settings. The poor efficacy of both cyclophotocoagulation treatments was most likely due to a lack of melanin in the setting of oculocutaneous albinism.
CONCLUSIONS AND IMPORTANCE
Cyclophotocoagulation in patients with oculocutaneous albinism is less likely to yield a desired lowering of intraocular pressure due to the absence of melanin.
PubMed: 38404485
DOI: 10.1016/j.ajoc.2024.102020 -
Journal of Personalized Medicine Nov 2023(1) Background: This study aims to highlight differences in the etiology and fitting of low vision aids in visually impaired children and adolescents in comparison to...
(1) Background: This study aims to highlight differences in the etiology and fitting of low vision aids in visually impaired children and adolescents in comparison to adults. (2) Methods: A retrospective data collection from visually impaired patients presenting to obtain assistive devices from 1 January 2016 to 30 April 2020 was conducted. A total of 502 patients were included. Inclusion criteria were a minimum age of 4 years and the chart notation of a best-corrected distance visual acuity in the patient record prior to the fitting of magnifying visual aids. (3) Results: Of the 502 patients, 147 (29.3%) were children under the age of 18 years. The most common cause of visual impairment in children was albinism, and in adults, it was age-related macular degeneration (AMD). Children showed better distance visual acuity, with a median of 0.88 logMAR (Logarithm of the Minimum Angle of Resolution) compared to 1.0 in adults ( = 0.001). Near visual acuity was also significantly better, with a median of 0.54 logMAR in children compared to 0.9 in adults ( < 0.001). Near and distance visual acuity were significantly improved by fitting magnifying visual aids ( < 0.001). After fitting, near visual acuity averaged 0.3 logMAR, and distance visual acuity, 0.7. The most commonly prescribed aids were optical vision aids, which 68.5% of the patients received; 43.8% received electronic aids. In children, optical aids were more frequently prescribed, and in adults, electronic and acoustic aids ( < 0.001). (4) Conclusion: Visually impaired patients can regain the ability to read and improve distance vision by using individually adapted and tested magnifying vision aids, often with optical aids alone. Differences between children and adults could be discovered in the etiology and severity of visual impairment, as well as in the provision type of low vision aids.
PubMed: 38003923
DOI: 10.3390/jpm13111608 -
Frontiers in Immunology 2024Lysosomes and lysosome related organelles (LROs) are dynamic organelles at the intersection of various pathways involved in maintaining cellular hemostasis and... (Review)
Review
Lysosomes and lysosome related organelles (LROs) are dynamic organelles at the intersection of various pathways involved in maintaining cellular hemostasis and regulating cellular functions. Vesicle trafficking of lysosomes and LROs are critical to maintain their functions. The lysosomal trafficking regulator (LYST) is an elusive protein important for the regulation of membrane dynamics and intracellular trafficking of lysosomes and LROs. Mutations to the LYST gene result in Chédiak-Higashi syndrome, an autosomal recessive immunodeficiency characterized by defective granule exocytosis, cytotoxicity, etc. Despite eight decades passing since its initial discovery, a comprehensive understanding of LYST's function in cellular biology remains unresolved. Accumulating evidence suggests that dysregulation of LYST function also manifests in other disease states. Here, we review the available literature to consolidate available scientific endeavors in relation to LYST and discuss its relevance for immunomodulatory therapies, regenerative medicine and cancer applications.
Topics: Humans; Lysosomes; Vesicular Transport Proteins; Animals; Chediak-Higashi Syndrome; Protein Transport; Mutation
PubMed: 38774881
DOI: 10.3389/fimmu.2024.1404846 -
European Journal of Ophthalmology May 2024The association between Autism spectrum disorders (ASD) and visual impairment has been mentioned in the literature. The aim of our study was to investigate the...
BACKGROUND
The association between Autism spectrum disorders (ASD) and visual impairment has been mentioned in the literature. The aim of our study was to investigate the prevalence of autism among children with albinism compared to the prevalence of ASD in children with visual impairment secondary to other causes.
METHODS
Retrospective study of children with albinism from January 2015 to December 2020. A control group was created with children with early onset visual impairment of similar visual range and age, secondary to diagnosis other than albinism. Patients with associated Autism were identified in both groups.
RESULTS
Seven hundred and eight children aged 1-18 years with visual impairment were included in the study. 401 children had a diagnosis of albinism, of whom 14 were also diagnosed with ASD. In the control group, composed of 307 patients, only 3 had ASD (p: 0·03).
CONCLUSIONS
The prevalence of ASD in patients with albinism was 1 in 28, while in children with visual impairment from other causes was 1 in 102. We aim to raise awareness of the higher prevalence of autism in children diagnosed with albinism in order to reach earlier diagnosis and support.
Topics: Humans; Retrospective Studies; Child; Prevalence; Male; Female; Child, Preschool; Adolescent; Infant; Visual Acuity; Albinism, Ocular; Autism Spectrum Disorder
PubMed: 37787167
DOI: 10.1177/11206721231206091 -
BMC Medicine Jan 2024To date, almost no research on the psychosocial implications of albinism has been conducted in France and an exploration of albinism-related experiences could be...
BACKGROUND
To date, almost no research on the psychosocial implications of albinism has been conducted in France and an exploration of albinism-related experiences could be beneficial, in order to better understand this condition. The aim of this study was to examine how French people with albinism and their parents live with and adapt to this condition in all the areas of their lives.
METHODS
Semi-structured phone interviews were conducted with 9 parent-child dyads, each participating separately. Participants were recruited by convenience sampling, thanks to the combined efforts of a patient association (Genespoir) and professionals from the partner medical referral centers involved in the project. Dyads in which the individual with albinism had any comorbidity were excluded. The interviews were then transcribed and subjected to in-depth thematic analysis. Two codebooks were constructed in a mirrored process: one for people with albinism; the other for their parents. They were finally merged at the end of the coding step.
RESULTS
Four main categories were identified: personal perceptions and social representations of albinism, difficulties and obstacles encountered by people with albinism, resources and facilitators, and the importance of parent-child functioning. The results indicated that experiences of stigmatization during childhood and adolescence are common and that people with albinism face challenges in adapting to certain obstacles related to their visual impairments (VI) (e.g., inability to drive a car; eye strain...). Parents emerged as one, if not as the main, source of support for people with albinism throughout their development. Although external support systems exist to assist them in various aspects of their lives, some of them primarily rely on their own personal resources to cope.
CONCLUSIONS
This research highlights the importance of a systemic and transdisciplinary approach to make sure families receive the support that best meets their needs.
Topics: Adolescent; Adult; Humans; Albinism; European People; France; Parents; Qualitative Research; Social Stigma; Family Support; Social Support
PubMed: 38281904
DOI: 10.1186/s12916-024-03251-z