Disease relevance of Albinism

• Mutation in and lack of expression of tyrosinase-related protein-1 (TRP-1) in melanocytes from an individual with brown oculocutaneous albinism: a new subtype of albinism classified as "OCA3" [1].
• Hermansky-Pudlak syndrome (HPS) consists of ocu-locutaneous albinism, a platelet storage-pool deficiency, and ceroid lipofuscinosis [2].
• The abnormalities in melanogenesis are associated with albinism, vitiligo, as well as malignant melanoma in humans [3].
• The occuloalbinism 2 (OCA2) gene, localized at 15q11, encodes a melanosomal transmembrane protein that is involved in the most common form of human occulo-cutaneous albinism, a human genetic disorder characterized by fair pigmentation and susceptibility to skin cancer [4].
• Ophthalmologists treating patients with albinism should consider HPS in their differential diagnosis even in the case of mild iris and macular hypopigmentation [5].

High impact information on Albinism

• We focused on the trait of albinism and discovered that it is linked to Oca2, a known pigmentation gene, in two cave populations [6].
• Since this gene with the coding capacity for tyrosinase is absent in all studied c-locus lethal deletion mutant mice, we have evidence that albinism in mice is caused by mutations of the tyrosinase gene [7].
• The Hermansky-Pudlak syndrome consists of tyrosine-positive albinism, a defect in the second phase of platelet aggregation, and widespread accumulation of a ceroidlike pigment in tissue [8].
• OCA3 (MIM 203290), a rare form of OCA and also known as "rufous/red albinism," is associated with mutations in TYRP1 (encoding tyrosinase-related protein 1) [9].
• Granulophysin levels were only low in forms of delta-SPD associated with albinism [10].

Chemical compound and disease context of Albinism

• Melanogenesis is regulated in large part by tyrosinase (monophenol monooxygenase; monophenol, L-dopa:oxygen oxidoreductase, EC 1.14.18.1), and defective tyrosinase leads to albinism [11].
• Neither the history of previous light exposure, albinism, nor elevated circulating testosterone levels could account for the interstrain difference in mean tau DD [12].
• The pineal hormone melatonin and the melanocyte-stimulating hormone inhibitory factor may be etiologic determinants of psychosis associated with albinism [13].
• Identification of compounds that bind mitochondrial F1F0 ATPase by screening a triazine library for correction of albinism [14].
• Tyrosinase, the primary enzyme in melanin synthesis commonly mutated in albinism, oxidizes l-tyrosine to l-dopaquinone using l-3,4-dihydroxyphenylalanine (L-DOPA) as an intermediate product [15].

Biological context of Albinism

• Aside from the albinism in the proband, his phenotype and that of his normally pigmented father is otherwise normal, suggesting that this TYR deletion does not involve other functionally important contiguous genes [16].
• Our findings provide insights into the genetics of albinism and HPS in PR, and provide the basis for genetic screening for these disorders in this minority population [17].
• Hermansky-Pudlak syndrome is a multisystem disorder with albinism, bleeding diathesis and visual impairment as the main features [18].
• BACKGROUND: Studies using the long-sleep (LS) X short-sleep (SS) (LSXSS) recombinant inbred mice and inbred long-sleep (ILS) by inbred short-sleep (ISS) intercrosses have found genetic linkage between Tyr albinism (c/c) and differential sensitivity to sedative-hypnotic doses of ethanol and general anesthetics [19].
• Strain distribution studies showed that Ly-21.2 is present in all strains examined, including B10, except the A strain and segregation analysis of (A/J x B10) F2 mice showed that Ly-21.2 expression (1) is encoded by one gene and (2) is linked to albinism on chromosome 7 [20].

Anatomical context of Albinism

• Hermansky-Pudlak syndrome (HPS) is a rare, often fatal, autosomal recessive disorder in which albinism, bleeding and lysosomal storage are associated with defects of diverse cytoplasmic organelles, including melanosomes, platelet dense granules and lysosomes [21].
• Mutations in tyrosinase lead to albinism due, at least in part, to aberrant retention of the protein in the endoplasmic reticulum and subsequent degradation by the cytosolic ubiquitin-proteasomal pathway [22].
• The Hermansky-Pudlak syndrome is an autosomal recessive disorder consisting of the triad of albinism, a bleeding diathesis, and ceroid deposition within the reticuloendothelial system [23].
• It is concluded that the visual pathway anomaly is limited to albinism and is not a likely cause of most human strabismus [24].

Gene context of Albinism

• All eight patients have mild symptoms of HPS; two Jewish patients had received the diagnosis of ocular, rather than oculocutaneous, albinism [25].
• RESULTS: Differently from other albinism models, Tyr activity was not impaired in Oa1-/- eyes [26].
• Although this QTL is tightly linked to Tyr, propofol sensitivity is not modulated by albinism [27].
• The lack of specificity for calnexin interaction reveals a novel role for calreticulin in OCAI albinism [28].
• D12S53E is a likely candidate gene for some cases of human oculocutaneous albinism not associated with known albinism loci [29].

Analytical, diagnostic and therapeutic context of Albinism

• In order to study the molecular aspects of albinism, we analyzed the expression of tyrosinase gene in some amelanotic mutant mice by Northern blotting using mouse tyrosinase cDNA as a probe [30].

References