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Oculocutaneous albinism
Published in Electra Nicolaidou, Clio Dessinioti, Andreas D. Katsambas, Hypopigmentation, 2019
Mira Kadurina, Anastasiya A. Chokoeva, Torello Lotti
Ocular albinism is associated with mutations in the GPR143 gene, resulting in dysfunctional melanosome biogenesis with “macromelanosomes.” The pigment dysfunction is limited to the eyes, and the ocular problems are severe, including nystagmus, foveal hypoplasia, and photophobia with impaired visual acuity. Pale skin may be seen in addition. Almost all of the female carriers show X-inactivation with pigmentary mosaicism in the retina, which is an important diagnostic clue for affected male children.5,8,9
Genotype-phenotype associations in Danish patients with ocular and oculocutaneous albinism
Published in Ophthalmic Genetics, 2021
Line Kessel, Birgit Kjer, Ulrikke Lei, Morten Duno, Karen Grønskov
Molecular genetic diagnostics in individuals with albinism is important because of the difficulties in distinguishing clinically between isolated forms of albinism and the syndromic forms where additional and severe symptoms may present later in life. Seven oculocutaneous, one ocular-only and several syndromic subtypes of albinism have been described (4). Oculo-cutaneous albinism has been subdivided into type I including OCA1A (OMIM#203100) and OCA1B (OMIM#606952) both caused by bi-allelic variants in TYR (7), type 2 (OMIM#203200) caused by bi-allelic variants in OCA2 (8), type 3 (OMIM#203290) caused by bi-allelic variants in TYRP1 (9), type 4 (OMIM#606574) caused by bi-allelic variants in SLC45A2 (10), type 5 (OMIM#615312) where the underlying genetic defect is still unknown but has been mapped to chromosome 4q24 (11), type 6 (OMIM# #113750) caused by bi-allelic variants in SLC24A5 (12), and type 7 (OMIM#615179) caused by bi-allelic variants in LRMDA (13). Ocular albinism, OA (OMIM#300500) is X-linked and caused by mono-allelic variants in GPR143 (14). Syndromic forms include Hermansky-Pudlak syndrome (10 different genes, recent updated by Huizing (15)), Chediak-Higashi syndrome (OMIM#214500) caused by bi-allelic variants in LYST (16) and Griscelli syndrome (three genes) (17).
The challenges faced by clinicians diagnosing and treating infantile nystagmus Part I: diagnosis
Published in Expert Review of Ophthalmology, 2021
Eleni Papageorgiou, Irene Gottlob
Infantile nystagmus is a genetically heterogeneous disorder, associated with mutations of genes expressed in the retina and brain. Recent discoveries in the field of nystagmus genetics have made molecular genetic testing an integral part of the nystagmus workup. The FRMD7 gene has been identified as the major cause of hereditary X-linked idiopathic infantile nystagmus (IIN). Autosomal recessive ocular albinism (AROA) is the most common form of albinism. GPR143 (OA1) is the gene associated with X-linked ocular albinism, In addition, a variety of retinal dystrophies associated with nystagmus can be diagnosed by means of genetic testing. Six genes have been identified for ACHM (CNGA3, CNGB3, GNAT2, PDE6C, PDE6H and ATF6). Mutations in the PAX6 gene cause a variety of dominantly transmitted ocular anomalies and nystagmus, such as aniridia, optic nerve malformations, colobomas, anterior segment dysgenesis, and foveal hypoplasia (OMIM 607,108). The combination of ocular phenotyping with recently developed next-generation sequencing (NGS) panels, for example for albinism, foveal hypoplasia, retinal dystrophies, or nystagmus, facilitates early diagnosis and enables accurate genetic counseling (Figure 4) [64–66].
The identification of small molecules that stimulate retinal pigment epithelial cells: potential novel therapeutic options for treating retinopathies
Published in Expert Opinion on Drug Discovery, 2019
Ana Artero-Castro, Stepan Popelka, Pavla Jendelova, Jan Motlik, Taras Ardan, Francisco Javier Rodriguez Jimenez, Slaven Erceg
Another small molecule drug candidate for the treatment of RPE malfunction is L-3,4-dihydroxyphenylalanine (L-DOPA). This compound is an intermediate of melanin synthesis in pigmented cells and is a highly selective ligand for an orphan G protein-coupled receptor (gene GPR143) [17]. The binding of L-DOPA to this receptor in RPE cells up-regulates the secretion of pigment epithelia-derived factor (PEDF) [17] and downregulates the secretion of VEGF [18]. This influence on trophic factor release is assumed to give protection from AMD progression. Indeed, a correlation between L-DOPA prescription and the delayed onset of either form of AMD has been found in a retrospective study [19]. A clinical study on the safety and efficacy of L-DOPA in AMD patients has recently been initiated (NCT03451500). Additionally, the physical and biological properties of the blood–retinal barrier (BRB) in vivo have to be taken into account in order to efficiently design small molecules for future therapy in humans [20,21]. The BRB features as well as the physical and dynamic factors of RPE cells could prevent or enable the efficient delivery, efficacy, and toxicity of compounds to the eye [20,21]. This problem could be circumvented by local, more direct delivery such as intravitreal administration, but this could produce more local side-effects such as pain at the site of injection [21].