Estimation of carrier frequency of a 2.7 kb deletion allele of the P gene associated with OCA2 in African-Americans

Institute for Cancer Research, Fox Chase Cancer Center, Philadelphia, Pennsylvania 19111, USA.
Human Mutation (Impact Factor: 5.05). 01/1996; 7(4):370-3. DOI: 10.1002/(SICI)1098-1004(1996)7:4<370::AID-HUMU15>3.0.CO;2-#
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    ABSTRACT: Abstract Purpose: To describe and compare ocular findings in patients with Hermansky-Pudlak syndrome (HPS) type 1 and 3. Methods: This is a retrospective case series of 64 patients with HPS from 1999 to 2009 evaluated at an outpatient private ophthalmologic clinic. Patients underwent genetic analysis of selected albinism (Tyrosine and P gene) and HPS genes (HPS-1 and HPS-3) by screening for common mutations and exon sequencing with DNA screening. Descriptive and non-parametric statistical analyses were carried out. Results: Nearly 70% of the patients were homozygous for common Puerto Rican mutations leading to the HPS1 gene (16-BP DUP, 53.6%), while 30% had the 3904-BP DEL HPS3 gene mutation. Best corrected visual acuity (BCVA) was poorer in patients with type 1 HPS than in patients with type 3 HPS (p < 0.001), esotropia was more common among type 1 HPS patients (p < 0.018), while exotropia was more common among patients with type 3 HPS. Total iris transillumination was more common in patients with type 1 HPS and minimal iris transillumination in patients with type 3 HPS (p < 0.001). The maculae were translucent in patients with type 1 HPS, while patients with type 3 HPS had opaque maculae (p < 0.001). Conclusions: Patients with type 1 HPS had poorer BCVA, increased incidence of esotropia, lighter iris and macular appearance. In contrast, patients with type 3 HPS had more exotropia. In addition, to our knowledge this is the largest series type 3 HPS ever reported.
    Ophthalmic Genetics 04/2014; DOI:10.3109/13816810.2014.907920 · 1.07 Impact Factor
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    ABSTRACT: Oculocutaneous albinism type 1 (OCA1) is characterized by reduced synthesis of melanin in the skin, hair, and eyes, associated with ocular findings of nystagmus, reduced iris pigment with iris translucency, reduced retinal pigment, foveal hypoplasia with significantly reduced visual acuity usually in the range of 20/100 to 20/400, and misrouting of the optic nerves resulting in alternating strabismus and reduced stereoscopic vision. Individuals with OCA1A have white hair, white skin that does not tan, and fully translucent irises that do not darken with age. At birth, individuals with OCA1B have white or very light yellow hair that darkens with age, white skin that over time develops some generalized pigment and may tan with sun exposure, and blue irises that change to green/hazel or brown/tan with age. Visual acuity may be 20/60 or better in some individuals. The diagnosis of OCA1 is established by clinical findings of hypopigmentation of the skin and hair and characteristic eye findings. Molecular genetic testing of the tyrosinase gene, TYR, is clinically available; it is rarely used in diagnosis and is most commonly used in genetic counseling for carrier detection. OCA1 is inherited in an autosomal recessive manner. At conception, the sibs of an affected individual have a 25% chance of being affected, a 50% chance of being asymptomatic carriers, and a 25% chance of being unaffected and not carriers. Prenatal diagnosis of OCA1 by fetal skin biopsy or molecular genetic testing is possible in pregnancies at 25% risk.
    GeneReviews™, Edited by Roberta A Pagon, Thomas D Bird, Cynthia R Dolan, Karen Stephens, Margaret P Adam; University of Washington, Seattle.
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    ABSTRACT: Oculocutaneous albinism (OCA) is caused by mutations in six different genes and their molecular diagnosis encompasses the search for point mutations and intragenic rearrangements. Here we used high resolution array-CGH to search for rearrangements across exons, introns and regulatory sequences of four OCA genes, TYR, OCA2, TYRP1, and SLC45A2. We identified a total of ten new deletions in TYR, OCA2, and SLC45A2. A complex rearrangement of OCA2 was found in two unrelated patients. Whole genome sequencing showed deletion of a 184 kb fragment (identical to a deletion previously found in polish patients), whereby a large portion of the deleted sequence was re-inserted after severe reshuffling into intron 1 of OCA2. The high-resolution CGH array presented here is a powerful tool to detect gene rearrangements. Finally, we review all known deletions of the OCA1-4 genes reported so far in the literature, and show that deletions or duplications account for 5.6% of all mutations identified in the OCA1-4 genes. This article is protected by copyright. All rights reserved.
    Pigment Cell & Melanoma Research 09/2013; DOI:10.1111/pcmr.12173 · 5.84 Impact Factor