Prospective Study of the Phenotypic and Mutational Spectrum of Ocular Albinism and Oculocutaneous Albinism.

Hwei Wuen Chan,Samantha Malka,Elena R Schiff,Vijay K Tailor,Mariya Moosajee,Maria Theodorou,Magella M Neveu

doi:10.3390/genes12040508

Abstract

Albinism encompasses a group of hereditary disorders characterized by reduced or absent ocular pigment and variable skin and/or hair involvement, with syndromic forms such as Hermansky–Pudlak syndrome and Chédiak–Higashi syndrome. Autosomal recessive oculocutaneous albinism (OCA) is phenotypically and genetically heterogenous (associated with seven genes). X-linked ocular albinism (OA) is associated with only one gene, GPR143. We report the clinical and genetic outcomes of 44 patients, from 40 unrelated families of diverse ethnicities, with query albinism presenting to the ocular genetics service at Moorfields Eye Hospital NHS Foundation Trust between November 2017 and October 2019. Thirty-six were children (≤ 16 years) with a median age of 31 months (range 2–186), and eight adults with a median age of 33 years (range 17–39); 52.3% (n = 23) were male. Genetic testing using whole genome sequencing (WGS, n = 9) or a targeted gene panel (n = 31) gave an overall diagnostic rate of 42.5% (44.4% (4/9) with WGS and 41.9% (13/31) with panel testing). Seventeen families had confirmed mutations in TYR (n = 9), OCA2, (n = 4), HPS1 (n = 1), HPS3 (n = 1), HPS6 (n = 1), and GPR143 (n = 1). Molecular diagnosis of albinism remains challenging due to factors such as missing heritability. Differential diagnoses must include SLC38A8-associated foveal hypoplasia and syndromic forms of albinism.

Highlights

Albinism encompasses a group of rare genetic disorders, frequently but not always associated with impaired melanosome maturation, melanin pigment synthesis, and distribution in melanocytes
The purpose of this study is to describe the phenotypic and genotypic spectrum of a cohort of 44 consecutive patients presenting to the ocular genetics service with suspected albinism
This was a prospective cohort study of consecutive nystagmus patients with suspected albinism presenting to the ocular genetic service at Moorfields Eye Hospital NHS Foundation Trust (MEH), London, United Kingdom, between November 2017 and October 2019

Summary

Introduction

Albinism encompasses a group of rare genetic disorders, frequently but not always associated with impaired melanosome maturation, melanin pigment synthesis, and distribution in melanocytes. Melanocytes are neural crest cells, which can be categorized into cutaneous (hair and skin) or extracutaneous (eye and cochlea). The posterior epithelial surface of the ciliary body (pars plana), sphincter, and dilator muscles of the iris and retinal pigment epithelium (RPE) are derived from the neuroectoderm. The choroid and uveal melanocytes as well as the hair and skin melanocytes are neural crest derived. Variations in melanosome composition and structure determine the degree of pigmentation of the eyes, hair, and skin. Ophthalmic manifestations of absent or reduced melanin pigment include iris hypopigmentation with a transillumination defect, foveal hypoplasia, hypopigmented fundus, and the hallmark finding of chiasmal misrouting (increased number of axons crossing the optic chiasm to innervate the contralateral cortex) on flash and pattern visual evoked potential (VEP)

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