{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T13:44:31Z","timestamp":1793108671650,"version":"4.5.0"},"reference-count":39,"publisher":"MDPI AG","issue":"14","license":[{"start":{"date-parts":[[2022,7,15]],"date-time":"2022-07-15T00:00:00Z","timestamp":1657843200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Oculocutaneous albinism is an autosomal recessive disorder characterized by the presence of typical ocular features, such as foveal hypoplasia, iris translucency, hypopigmented fundus oculi and reduced pigmentation of skin and hair. Albino patients can show significant clinical variability; some individuals can present with only mild depigmentation and subtle ocular changes. Here, we provide a retrospective review of the standardized clinical charts of patients firstly addressed for evaluation of foveal hypoplasia and slightly subnormal visual acuity, whose diagnosis of albinism was achieved only after extensive phenotypic and genotypic characterization. Our report corroborates the pathogenicity of the two common TYR polymorphisms p.(Arg402Gln) and p.(Ser192Tyr) when both are located in trans with a pathogenic TYR variant and aims to expand the phenotypic spectrum of albinism in order to increase the detection rate of the albino phenotype. Our data also suggest that isolated foveal hypoplasia should be considered a clinical sign instead of a definitive diagnosis of an isolated clinical entity, and we recommend deep phenotypic and molecular characterization in such patients to achieve a proper diagnosis.<\/jats:p>","DOI":"10.3390\/ijms23147825","type":"journal-article","created":{"date-parts":[[2022,7,17]],"date-time":"2022-07-17T22:57:06Z","timestamp":1658098626000},"page":"7825","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Expanding the Spectrum of Oculocutaneous Albinism: Does Isolated Foveal Hypoplasia Really Exist?"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4113-0736","authenticated-orcid":false,"given":"Camilla","family":"Rocca","sequence":"first","affiliation":[{"name":"Department of Biomedical Experimental and Clinical Sciences \u201cMario Serio\u201d, University of Florence, 50121 Florence, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4365-0172","authenticated-orcid":false,"given":"Lucia","family":"Tiberi","sequence":"additional","affiliation":[{"name":"Department of Biomedical Experimental and Clinical Sciences \u201cMario Serio\u201d, University of Florence, 50121 Florence, Italy"},{"name":"Medical Genetics Unit, Meyer University Hospital, 50139 Florence, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Bargiacchi","sequence":"additional","affiliation":[{"name":"Medical Genetics Unit, Meyer University Hospital, 50139 Florence, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7800-8094","authenticated-orcid":false,"given":"Viviana","family":"Palazzo","sequence":"additional","affiliation":[{"name":"Medical Genetics Unit, Meyer University Hospital, 50139 Florence, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7423-0325","authenticated-orcid":false,"given":"Samuela","family":"Landini","sequence":"additional","affiliation":[{"name":"Medical Genetics Unit, Meyer University Hospital, 50139 Florence, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6676-9379","authenticated-orcid":false,"given":"Elisa","family":"Marziali","sequence":"additional","affiliation":[{"name":"Pediatric Ophthalmology Unit, Children\u2019s Hospital A, Meyer-University of Florence, 50139 Florence, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberto","family":"Caputo","sequence":"additional","affiliation":[{"name":"Pediatric Ophthalmology Unit, Children\u2019s Hospital A, Meyer-University of Florence, 50139 Florence, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7755-5114","authenticated-orcid":false,"given":"Francesca","family":"Tinelli","sequence":"additional","affiliation":[{"name":"Department of Developmental Neuroscience, IRCCS Stella Maris Foundation, 56128 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0900-5206","authenticated-orcid":false,"given":"Viviana","family":"Marchi","sequence":"additional","affiliation":[{"name":"Department of Developmental Neuroscience, IRCCS Stella Maris Foundation, 56128 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandro","family":"Benedetto","sequence":"additional","affiliation":[{"name":"Department of Developmental Neuroscience, IRCCS Stella Maris Foundation, 56128 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angelica","family":"Pagliazzi","sequence":"additional","affiliation":[{"name":"Medical Genetics Unit, Meyer University Hospital, 50139 Florence, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8741-4833","authenticated-orcid":false,"given":"Giacomo Maria","family":"Bacci","sequence":"additional","affiliation":[{"name":"Pediatric Ophthalmology Unit, Children\u2019s Hospital A, Meyer-University of Florence, 50139 Florence, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,7,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"800","DOI":"10.1086\/301776","article-title":"OA1 Mutations and Deletions in X-Linked Ocular Albinism","volume":"62","author":"Schnur","year":"1998","journal-title":"Am. J. Hum. Genet."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"479","DOI":"10.1038\/s41436-020-00997-8","article-title":"Dopachrome tautomerase variants in patients with oculocutaneous albinism","volume":"23","author":"Pennamen","year":"2020","journal-title":"Genet. Med."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Gr\u00f8nskov, K., Ek, J., and Brondum-Nielsen, K. (2007). Oculocutaneous albinism. Orphanet J. Rare Dis., 2.","DOI":"10.1186\/1750-1172-2-43"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"503","DOI":"10.1016\/j.abd.2019.09.023","article-title":"Albinism: Epidemiology, genetics, cutaneous characterization, psychosocial factors","volume":"94","author":"Maia","year":"2019","journal-title":"An. Bras. Dermatol."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Campbell, P., Ellingford, J.M., Parry, N.R.A., Fletcher, T., Ramsden, S.C., Gale, T., Hall, G., Smith, K., Kasperaviciute, D., and Thomas, E. (2019). Clinical and genetic variability in children with partial albinism. Sci. Rep., 9.","DOI":"10.1038\/s41598-019-51768-8"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1953","DOI":"10.1016\/j.ophtha.2018.08.003","article-title":"The Phenotypic Spectrum of Albinism","volume":"125","author":"Kruijt","year":"2018","journal-title":"Ophthalmology"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"552","DOI":"10.1111\/pcmr.12253","article-title":"Molecular analysis of common polymorphisms within the human Tyrosinase locus and genetic association with pigmentation traits","volume":"27","author":"Jagirdar","year":"2014","journal-title":"Pigment Cell Melanoma Res."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Norman, C., O\u2019Gorman, L., Gibson, J., Pengelly, R., Baralle, D., Ratnayaka, J.A., Griffiths, H., Rose-Zerilli, M., Ranger, M., and Bunyan, D. (2017). Identification of a functionally significant tri-allelic genotype in the Tyrosinase gene (TYR) causing hypomorphic oculocutaneous albinism (OCA1B). Sci. Rep., 7.","DOI":"10.1038\/s41598-017-04401-5"},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Gr\u00f8nskov, K., Jespersgaard, C., Bruun, G.H., Harris, P., Br\u00f8ndum-Nielsen, K., Andresen, B.S., and Rosenberg, T. (2019). A pathogenic haplotype, common in Europeans, causes autosomal recessive albinism and uncovers missing heritability in OCA1. Sci. Rep., 9.","DOI":"10.1038\/s41598-018-37272-5"},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Lin, S., Sanchez-Breta\u00f1o, A., Leslie, J.S., Williams, K.B., Lee, H., Thomas, N.S., Callaway, J., Deline, J., Ratnayaka, J.A., and Baralle, D. (2022). Evidence that the Ser192Tyr\/Arg402Gln in cis Tyrosinase gene haplotype is a disease-causing allele in oculocutaneous albinism type 1B (OCA1B). npj Genom. Med., 7.","DOI":"10.1038\/s41525-021-00275-9"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1038\/jhg.2015.167","article-title":"Homozygosity mapping in albinism patients using a novel panel of 13 STR markers inside the nonsyndromic OCA genes: Introducing 5 novel mutations","volume":"61","author":"Akbari","year":"2016","journal-title":"J. Hum. Genet."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Camand, O., Marchant, D., Boutboul, S., P\u00e9quignot, M., Odent, S., Dollfus, H., Sutherland, J., Levin, A., Menasche, M., and Marsac, C. (2001). Mutation analysis of the tyrosinase gene in oculocutaneous albinism. Hum. Mutat., 17.","DOI":"10.1002\/humu.38"},{"key":"ref_13","first-page":"17","article-title":"A frequent tyrosinase gene mutation associated with type I-A (tyrosinase-negative) oculocutaneous albinism in Puerto Rico","volume":"52","author":"Oetting","year":"1993","journal-title":"Am. J. Hum. Genet."},{"key":"ref_14","first-page":"123","article-title":"Detection of point mutation in the tyrosinase gene of a Japanese albino patient by a direct sequencing of amplified DNA","volume":"85","author":"Kikuchi","year":"1990","journal-title":"Qual. Life Res."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"672","DOI":"10.1111\/pcmr.12790","article-title":"Comprehensive analysis of spectral distribution of a large cohort of Chinese patients with non-syndromic oculocutaneous albinism facilitates genetic diagnosis","volume":"32","author":"Zhong","year":"2019","journal-title":"Pigment Cell Melanoma Res."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"260","DOI":"10.1016\/j.jdermsci.2014.09.011","article-title":"Oculocutaneous albinism (OCA) in Colombia: First molecular screening of the TYR and OCA2 genes in South America","volume":"76","author":"Urtatiz","year":"2014","journal-title":"J. Dermatol. Sci."},{"key":"ref_17","first-page":"199","article-title":"Three different frameshift mutations of the tyrosinase gene in type IA oculocutaneous albinism","volume":"49","author":"Oetting","year":"1991","journal-title":"Am. J. Hum. Genet."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"318","DOI":"10.1111\/pcmr.12651","article-title":"Lessons of a day hospital: Comprehensive assessment of patients with albinism in a European setting","volume":"31","author":"Marti","year":"2017","journal-title":"Pigment Cell Melanoma Res."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/0009-8981(94)90131-7","article-title":"Initiation codon mutation of the tyrosinase gene as a cause of human albinism","volume":"227","author":"Breimer","year":"1994","journal-title":"Clin. Chim. Acta"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Kars, M.E., Ba\u015fak, A.N., Onat, O.E., Bilguvar, K., Choi, J., Itan, Y., \u00c7a\u011flar, C., Palvadeau, R., Casanova, J.-L., and Cooper, D.N. (2021). The genetic structure of the Turkish population reveals high levels of variation and admixture. Proc. Natl. Acad. Sci. USA, 118.","DOI":"10.1073\/pnas.2026076118"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1097\/00041327-200103000-00007","article-title":"A Girl Without a Chiasm: Electrophysiologic and MRI Evidence for the Absence of Crossing Optic Nerve Fibers in a Girl With a Congenital Nystagmus","volume":"21","author":"Jansonius","year":"2001","journal-title":"J. Neuro-Ophthalmol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1016\/S0166-4328(05)80194-9","article-title":"Detection and maturation of VEP albino asymmetry: An overview and a longitudinal study from birth to 54 weeks","volume":"49","author":"Apkarian","year":"1992","journal-title":"Behav. Brain Res."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1136\/bjo.74.3.136","article-title":"Albinism in childhood: A flash VEP and ERG study","volume":"74","author":"Kriss","year":"1990","journal-title":"Br. J. Ophthalmol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"3963","DOI":"10.1167\/iovs.19-27364","article-title":"The Detection Of Misrouting In Albinism: Evaluation of Different VEP Procedures in a Heterogeneous Cohort","volume":"60","author":"Kruijt","year":"2019","journal-title":"Investig. Opthalmol. Vis. Sci."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"193","DOI":"10.3109\/13816819009020979","article-title":"Visual anomalies associated with albinism","volume":"11","author":"Creel","year":"1990","journal-title":"Ophthalmic Paediatr. Genet."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1023\/A:1022526409674","article-title":"Chiasmal coefficient of flash and pattern visual evoked potentials for detection of chiasmal misrouting in albinism","volume":"106","author":"Pott","year":"2003","journal-title":"Doc. Ophthalmol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1167\/iovs.02-0156","article-title":"Configuration of the Optic Chiasm in Humans with Albinism as Revealed by Magnetic Resonance Imaging","volume":"44","author":"Schmitz","year":"2003","journal-title":"Investig. Opthalmol. Vis. Sci."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"990","DOI":"10.1016\/0006-291X(89)91767-1","article-title":"Human oculocutaneous albinism caused by single base insertion in the tyrosinase gene","volume":"164","author":"Tomita","year":"1989","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"610","DOI":"10.1016\/j.jaapos.2009.09.015","article-title":"Ocular albinism with absent foveal pits but without nystagmus, photophobia, or severely reduced vision","volume":"13","author":"Kubal","year":"2009","journal-title":"J. Am. Assoc. Pediatr. Ophthalmol. Strabismus"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"543","DOI":"10.1038\/s10038-020-00872-z","article-title":"Novel compound heterozygous variants of tyrosinase gene in an isolated foveal hypoplasia patient without nystagmus","volume":"66","author":"Xu","year":"2020","journal-title":"J. Hum. Genet."},{"key":"ref_31","first-page":"2165","article-title":"A new recessively inherited disorder composed of foveal hypoplasia, optic nerve decussation defects and anterior segment dysgenesis maps to chromosome 16q23.3-24.1","volume":"19","author":"Pal","year":"2013","journal-title":"Mol. Vis."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1653","DOI":"10.1016\/j.ophtha.2011.01.028","article-title":"Structural Grading of Foveal Hypoplasia Using Spectral-Domain Optical Coherence Tomography: A Predictor of Visual Acuity?","volume":"118","author":"Thomas","year":"2011","journal-title":"Ophthalmology"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"981","DOI":"10.1016\/j.ajhg.2016.03.018","article-title":"A Restricted Repertoire of De Novo Mutations in ITPR1 Cause Gillespie Syndrome with Evidence for Dominant-Negative Effect","volume":"98","author":"McEntagart","year":"2016","journal-title":"Am. J. Hum. Genet."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1093\/bib\/bbs017","article-title":"Integrative Genomics Viewer (IGV): High-performance genomics data visualization and exploration","volume":"14","author":"Robinson","year":"2013","journal-title":"Brief. Bioinform."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1297","DOI":"10.1101\/gr.107524.110","article-title":"The Genome Analysis Toolkit: A MapReduce framework for analyzing next-generation DNA sequencing data","volume":"20","author":"McKenna","year":"2010","journal-title":"Genome Res."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"2078","DOI":"10.1093\/bioinformatics\/btp352","article-title":"1000 Genome Project Data Processing Subgroup. The Sequence Alignment\/Map format and SAMtools","volume":"25","author":"Li","year":"2009","journal-title":"Bioinformatics"},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Wang, K., Li, M., and Hakonarson, H. (2010). ANNOVAR: Functional annotation of genetic variants from high-throughput sequencing data. Nucleic Acids Res., 38.","DOI":"10.1093\/nar\/gkq603"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"89","DOI":"10.2215\/CJN.06060519","article-title":"Reverse Phenotyping after Whole-Exome Sequencing in Steroid-Resistant Nephrotic Syndrome","volume":"15","author":"Landini","year":"2019","journal-title":"Clin. J. Am. Soc. Nephrol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1038\/gim.2015.30","article-title":"Standards and guidelines for the interpretation of sequence variants: A joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology","volume":"17","author":"Richards","year":"2015","journal-title":"Genet. Med."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/14\/7825\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T23:51:35Z","timestamp":1760140295000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/14\/7825"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,7,15]]},"references-count":39,"journal-issue":{"issue":"14","published-online":{"date-parts":[[2022,7]]}},"alternative-id":["ijms23147825"],"URL":"https:\/\/doi.org\/10.3390\/ijms23147825","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,7,15]]}}}