Molecular and clinical characterization of albinism in a large cohort of Italian patients

Abstract

Purpose: The purpose of this study was to identify the molecular basis of albinism in a large cohort of Italian patients showing typical ocular landmarks of the disease and to provide a full characterization of the clinical ophthalmic manifestations.

Methods: DNA samples from 45 patients with ocular manifestations of albinism were analyzed by direct sequencing analysis of five genes responsible for albinism: TYR, P, TYRP1, SLC45A2 (MATP), and OA1. All patients studied showed a variable degree of skin and hair hypopigmentation. Eighteen patients with distinct mutations in each gene associated with OCA were evaluated by detailed ophthalmic analysis, optical coherence tomography (OCT), and fundus autofluorescence.

Results: Disease-causing mutations were identified in more than 95% of analyzed patients with OCA (28/45 [62.2%] cases with two or more mutations; 15/45 [33.3%] cases with one mutation). Thirty-five different mutant alleles were identified of which 15 were novel. Mutations in TYR were the most frequent (73.3%), whereas mutations in P occurred more rarely (13.3%) than previously reported. Novel mutations were also identified in rare loci such as TYRP1 and MATP. Mutations in the OA1 gene were not detected. Clinical assessment revealed that patients with iris and macular pigmentation had significantly higher visual acuity than did severe hypopigmented phenotypes.

Conclusions: TYR gene mutations represent a relevant cause of oculocutaneous albinism in Italy, whereas mutations in P present a lower frequency than that found in other populations. Clinical analysis revealed that the severity of the ocular manifestations depends on the degree of retinal pigmentation.

Figure 1.

Distribution of mutated genes involved in albinism based on the results of mutational analysis in our cohort of patients.

Figure 2.

Fundus photography, FAF, and OCT analysis in four patients with mutations in different OCA genes: P3 (A, E, I), carrying TYR mutation; P36 (B, F, J) bearing a P mutation; P40 (C, G, K) with a TYRP1 mutation; and P41 (D, H, L) showing an MATP mutation (see Table 1). (A–D) Fundus photographs: choroidal vessels are visible in the macula in P3 (A) and P41 (D), but they are not visible in P36 (B) and P40 (C); (E–H) FAF: please note the absence of macular pigment in P3 (E) and P41 (H) and the presence of macular pigment in P36 (F) and P40 (G). (I–L) OCT of the posterior pole crossing the fovea, showing absence of the foveal pit in P3 (I) and P41 (L) and presence of the foveal pit in patients P36 (J) and P40 (K).