Ocular albinism type 1

Classification according to ICD-10
E70.3	Albinism
ICD-10 online (WHO version 2019)

The Ocular albinism type 1 (OA1) is an X-linked inherited condition in which all of the symptoms relating to the eyes of albino occur while the body is pigmented normal. Other names for OA1 and the associated genes are: Nettleship Falls Syndrome; Nettleship-Falls Type Ocular Albinism, G Protein-Coupled Receptor 143, GPR143 .

Symptoms

Men and homozygous women with OA1 have an eye fundus (Latin fundus oculi ) that lacks the pigment melanin , eye tremors ( nystagmus ) and can only see poorly. The junction of the optic nerves is also not developed normally. The skin, on the other hand, is hardly affected and a slight lightening is only noticeable in comparison with unaffected relatives.

In heterozygous women who have a healthy gene and a mutated gene, parts of the retina are normally pigmented while others lack color. This is due to the fact that the gene in one and the other X chromosome is inactivated in a random pattern .

Genetics and Cell Physiology

The OA1 gene (GPR143) is located in the area between Xp22.3-p22.2 on the X chromosome and codes for the G protein-coupled receptor 143, the ligand of which is currently unknown. While most G-protein-coupled receptors are located in the cell membrane , the G-protein-coupled receptor 143 is found in the melanocyte membrane .

The dye-forming cells ( melanocytes ) in people with OA1 have enlarged melanosomes ( organelles with the dye melanin), so-called macromelanosomes, both in the eyes and in the skin . In cases of doubt, this can be used to distinguish ocular albinism from atypical cases of mutations in other albinism loci. In contrast, the number of melanosomes is reduced.

The OA1 gene plays a regulatory role in the transport of melanosomes. In cells with an inoperable OA1 gene, the melanosomes move less often overall. In addition, the mutation also means that the melanosomes are mainly located in the cell periphery and not mainly in the central cytoplasm as in the wild type.

The OA1 gene affects the development of melanosomes in two places. On the one hand, it regulates their number during development so that significantly fewer melanosomes are formed with a zero mutation. Towards the end of development, it helps ensure that melanosomes get the correct size, so that enlarged melanosomes result in a null mutation.

The mutations that lead to OA1 can be divided into two groups. While group 1 mutations are normally produced and transported to their destination, but do not fulfill their function there. On the other hand, group 2 mutations lead to the fact that the receptor is indeed produced in the endoplasmic reticulum , as is also the case with the non-mutated variant, but is not transported from there to the melanosome and therefore cannot fulfill its task. There are also mutations in which no protein is produced because a large part or the entire gene is missing. Regardless of the origin of OA1, the albinism of the affected person is always equally pronounced.

Individual evidence

1. ↑ ^{a b c d} Ocular albinism type 1.  In: Online Mendelian Inheritance in Man . (English)
2. ↑ ^{a b c} M. d'Addio, A. Pizzigoni, MT Bassi, C. Baschirotto, C. Valetti, B. Incerti, M. Clementi, M. De Luca, A. Ballabio, MV Schiaffino: Defective intracellular transport and processing of OA1 is a major cause of ocular albinism type 1. In: Hum Mol Genet . 2000 Dec 12; 9 (20), 3011-3018. PMID 11115845
3. ↑ ^{a b c} Katia Cortese, Francesca Giordano, Enrico M. Surace, Consuelo Venturi, Andrea Ballabio, Carlo Tacchetti and Valeria Marigo: The Ocular Albinism Type 1 (OA1) Gene Controls Melanosome Maturation and Size. In: Invest Ophthalmol Vis Sci. 2005 Dec; 46 (12), pp. 4358-4364. doi: 10.1167 / iovs.05-0834 PMID 16303920
4. ^ I. Palmisano, P. Bagnato, A. Palmigiano, G. Innamorati, G. Rotondo, D. Altimare, C. Venturi, EV Sviderskaya, R. Piccirillo, M. Coppola, V. Marigo, B. Incerti, A. Ballabio, EM Surace, C. Tacchetti, DC Bennett, MV Schiaffino: The ocular albinism type 1 protein, an intracellular G protein-coupled receptor, regulates melanosome transport in pigment cells. In: Hum Mol Genet. 2008 Nov 15; 17 (22), pp. 3487-3501. Epub 2008 Aug 12. PMID 18697795

This article is about a health issue. It is not used for self-diagnosis and does not replace a diagnosis by a doctor. Please note the information on health issues !