Molecular and clinical characterization of albinism in a large cohort of Italian patients.
OBJECTIVE
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.
Gargiulo
Annagiusi
A
Telethon Institute of Genetics and Medicine (TIGEM), Naples, Italy.
Testa
Francesco
F
Rossi
Settimio
S
Di Iorio
Valentina
V
Fecarotta
Simona
S
de Berardinis
Teresa
T
Iovine
Antonello
A
Magli
Adriano
A
Signorini
Sabrina
S
Fazzi
Elisa
E
Galantuomo
Maria Silvana
MS
Fossarello
Maurizio
M
Montefusco
Sandro
S
Ciccodicola
Alfredo
A
Neri
Alberto
A
Macaluso
Claudio
C
Simonelli
Francesca
F
Surace
Enrico Maria
EM
D000293:Adolescent; D000328:Adult; D016115:Albinism, Oculocutaneous / Q000175:diagnosis / Q000235:genetics*; D000483:Alleles; D000951:Antigens, Neoplasm / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D005136:Eye Proteins / Q000235:genetics*; D005260:Female; D005451:Fluorescein Angiography; D006801:Humans; D007558:Italy; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics*; D026901:Membrane Transport Proteins / Q000235:genetics*; D008875:Middle Aged; D014442:Monophenol Monooxygenase / Q000235:genetics*; D009154:Mutation; D010088:Oxidoreductases / Q000235:genetics*; D016133:Polymerase Chain Reaction; D041623:Tomography, Optical Coherence; D055815:Young Adult
D000951:Antigens, Neoplasm; D005136:Eye Proteins; C095276:GPR143 protein, human; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; C489600:OCA2 protein, human; C510061:SLC45A2 protein, human; D010088:Oxidoreductases; C489799:TYRP1 protein, human; D014442:Monophenol Monooxygenase