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Archives of Disease in Childhood Jun 1999
Review
Topics: Albinism, Oculocutaneous; Humans; Infant; Melanins; Phenotype; Retina
PubMed: 10332009
DOI: 10.1136/adc.80.6.565 -
The Journal of Investigative Dermatology Nov 1994Oculocutaneous albinism (OCA) is a complex group of genetic disorders that have historically been defined by clinical and biochemical methods. Recent advances in the... (Review)
Review
Oculocutaneous albinism (OCA) is a complex group of genetic disorders that have historically been defined by clinical and biochemical methods. Recent advances in the molecular biology of pigmentation have greatly increased our understanding of the complexity of this group of disorders. To date, two different types of OCA (OCA1 and OCA2) have been mapped to specific chromosomal regions. Mutations have been found in the tyrosinase locus associated with OCA1 and the human homologue to the murine pink-eyed dilution locus associated with OCA2. Analysis of these genes and their mutations will allow us to better define and categorize the different types of albinism. Further, the analysis of these genes and their mutations will provide information on the role of these gene products in melanin biosynthesis and the effect specific mutations have on the pathogenesis of albinism.
Topics: Albinism, Oculocutaneous; Base Sequence; Humans; Molecular Sequence Data; Monophenol Monooxygenase; Mutation; Phenotype; Terminology as Topic
PubMed: 7963676
DOI: 10.1111/1523-1747.ep12399447 -
Journal of Vision Jun 2020The human fovea lies at the center of the retina and supports high-acuity vision. In normal visual system development, the highest acuity is correlated with both a high...
The human fovea lies at the center of the retina and supports high-acuity vision. In normal visual system development, the highest acuity is correlated with both a high density of cone photoreceptors in the fovea and a magnified retinotopic representation of the fovea in the visual cortex. Both cone density and the cortical area dedicated to each degree of visual space-the latter describing cortical magnification (CM)-steadily decrease with increasing eccentricity from the fovea. In albinism, peak cone density at the fovea and visual acuity are decreased, but seem to be within normal limits in the periphery, thus providing a model to explore the correlation between retinal structure, cortical structure, and behavior. Here, we used adaptive optics scanning light ophthalmoscopy to assess retinal cone density and functional magnetic resonance imaging to measure CM in the primary visual cortex of normal controls and individuals with albinism. We find that retinotopic organization is more varied among individuals with albinism than previously appreciated. Additionally, CM outside the fovea is similar to that in controls, but also more variable. CM in albinism and controls exceeds that which might be predicted based on cone density alone, but is more accurately predicted by retinal ganglion cell density. This finding suggests that decreased foveal cone density in albinism may be partially counteracted by nonuniform connectivity between cones and their downstream signaling partners. Together, these results emphasize that central as well as retinal factors must be included to provide a complete picture of aberrant structure and function in albinism.
Topics: Adolescent; Adult; Albinism; Cell Count; Female; Humans; Magnetic Resonance Imaging; Male; Ophthalmoscopy; Optics and Photonics; Retina; Retinal Cone Photoreceptor Cells; Retinal Ganglion Cells; Visual Acuity; Visual Cortex; Young Adult
PubMed: 32543650
DOI: 10.1167/jov.20.6.10 -
Genes Mar 2022Oculocutaneous albinism (OCA) is associated with a wide range of clinical presentations and has been categorized with syndromic and non-syndromic features. The most...
Oculocutaneous albinism (OCA) is associated with a wide range of clinical presentations and has been categorized with syndromic and non-syndromic features. The most common causative genes in non-syndromic OCA are TYR and OCA2 and HSP1 is in the syndromic albinism. The objective of this study was to identify pathogenic variants in congenital OCA families from Pakistan. Eight consanguineous families were recruited, and clinical and ophthalmological examination was carried out to diagnose the disease. Whole blood was collected from the participating individuals, and genomic DNA was extracted for sequencing analysis. TruSight one-panel sequencing was carried out on one affected individual of each family, and termination Sanger sequencing was carried out to establish the co-segregation of the causative gene or genes. In silico analysis was conducted to predict the causative pathogenic variants. Two families were found to have novel genetic pathogenic variants, and six families harbored previously reported variants. One novel compound heterozygous pathogenic variant in the TYR gene, c.1002delA; p.Ala335LeufsTer20, a novel frameshift deletion pathogenic variant and c.832C>T; and p.Arg278Ter (a known pathogenic variant) were found in one family, whereas HPS1; c.437G>A; and p.Trp146Ter were detected in another family. The identification of new and previous pathogenic variants in TYR, OCA2, and HPS1 genes are causative of congenital OCA, and these findings are expanding the heterogeneity of OCA.
Topics: Albinism, Oculocutaneous; Asian People; Humans; Membrane Proteins; Membrane Transport Proteins; Monophenol Monooxygenase; Pakistan; Pedigree
PubMed: 35328057
DOI: 10.3390/genes13030503 -
Dermatology Online Journal Dec 2003There are several syndromes of albinism associated with systemic pathology. These include Chediak-Higashi Syndrome (CHS), Hermansky-Pudlack Syndrome (HPS), Griscelli... (Review)
Review
There are several syndromes of albinism associated with systemic pathology. These include Chediak-Higashi Syndrome (CHS), Hermansky-Pudlack Syndrome (HPS), Griscelli Syndrome (GS), Elejalde Syndrome (ES) and Cross-McKusick-Breen Syndrome (CMBS). In the last several years the genetic defects underlying some of these syndromes have been described. HPS is related to 7 genes in humans. GS is related to 3 genes: MYOVA, Rab-27A, and melanophilin (Mlph). CHS is related to one gene: LYST. The genetic defects in ES and CMBS are yet to be defined. Syndromic forms of albinism are associated with defects in the packaging of melanin and other cellular proteins. As such they are distinct from oculocutaneous albinism, which is associated with defects in the production of melanin (e.g., TRP1, P gene, and tyrosinase).
Topics: Albinism; Animals; Chediak-Higashi Syndrome; Chromosomes, Human; Genes, Recessive; Genetic Heterogeneity; Genotype; Hermanski-Pudlak Syndrome; Humans; Mice; Mice, Mutant Strains; Phenotype; Species Specificity; Syndrome
PubMed: 14996378
DOI: No ID Found -
BioMed Research International 2014Oculocutaneous albinism (OCA) is an autosomal recessive disorder caused by either complete lack of or a reduction of melanin biosynthesis in the melanocytes. The OCA1A... (Review)
Review
Oculocutaneous albinism (OCA) is an autosomal recessive disorder caused by either complete lack of or a reduction of melanin biosynthesis in the melanocytes. The OCA1A is the most severe type with a complete lack of melanin production throughout life, while the milder forms OCA1B, OCA2, OCA3, and OCA4 show some pigment accumulation over time. Mutations in TYR, OCA2, TYRP1, and SLC45A2 are mainly responsible for causing oculocutaneous albinism. Recently, two new genes SLC24A5 and C10orf11 are identified that are responsible to cause OCA6 and OCA7, respectively. Also a locus has been mapped to the human chromosome 4q24 region which is responsible for genetic cause of OCA5. In this paper, we summarized the clinical and molecular features of OCA genes. Further, we reviewed the screening of pathological mutations of OCA genes and its molecular mechanism of the protein upon mutation by in silico approach. We also reviewed TYR (T373K, N371Y, M370T, and P313R), OCA2 (R305W), TYRP1 (R326H and R356Q) mutations and their structural consequences at molecular level. It is observed that the pathological genetic mutations and their structural and functional significance of OCA genes will aid in development of personalized medicine for albinism patients.
Topics: Albinism, Oculocutaneous; Antigens, Neoplasm; DNA Mutational Analysis; Humans; Melanins; Membrane Glycoproteins; Membrane Transport Proteins; Oxidoreductases; Pigment Epithelium of Eye
PubMed: 25093188
DOI: 10.1155/2014/905472 -
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 -
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 -
Translational Vision Science &... May 2021Adaptive optics scanning light ophthalmoscopy (AOSLO) imaging in patients with achromatopsia (ACHM) and albinism is not always successful. Here, we tested whether...
PURPOSE
Adaptive optics scanning light ophthalmoscopy (AOSLO) imaging in patients with achromatopsia (ACHM) and albinism is not always successful. Here, we tested whether optical coherence tomography (OCT) measures of foveal structure differed between patients for whom AOSLO images were either quantifiable or unquantifiable.
METHODS
The study included 166 subjects (84 with ACHM; 82 with albinism) with previously acquired OCT scans, AOSLO images, and best-corrected visual acuity (BCVA, if available). Foveal OCT scans were assessed for outer retinal structure, outer nuclear layer thickness, and hypoplasia. AOSLO images were graded as quantifiable if a peak cone density could be measured and/or usable if the location of peak density could be identified and the parafoveal mosaic was quantifiable.
RESULTS
Forty-nine percent of subjects with ACHM and 57% of subjects with albinism had quantifiable AOSLO images. Older age and better BCVA were found in subjects with quantifiable AOSLO images for both ACHM (P = 0.0214 and P = 0.0276, respectively) and albinism (P = 0.0073 and P < 0.0004, respectively). There was a significant trend between ellipsoid zone appearance and ability to quantify AOSLO (P = 0.0028). In albinism, OCT metrics of cone structure did not differ between groups.
CONCLUSIONS
Previously reported AOSLO-based cone density measures in ACHM may not necessarily reflect the degree of remnant cone structure in these patients.
TRANSLATIONAL RELEVANCE
Until AOSLO is successful in all patients with ACHM and albinism, the possibility of the reported data from a particular cohort not being representative of the entire population remains an important issue to consider when interpreting results from AOSLO studies.
Topics: Aged; Albinism; Benchmarking; Color Vision Defects; Humans; Ophthalmoscopy; Visual Acuity
PubMed: 34111268
DOI: 10.1167/tvst.10.6.22 -
The Journal of Investigative Dermatology Jul 2020
Topics: Albinism, Oculocutaneous; Diagnosis, Differential; Female; Heterozygote; Humans; Molecular Diagnostic Techniques; Ophthalmology; Phenotype; Pregnancy; Prenatal Diagnosis; Syndrome
PubMed: 31883962
DOI: 10.1016/j.jid.2019.12.010