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

{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.