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Oculocutaneous Albinism Type 2 (OCAII) via the OCA2 Gene

Summary and Pricing

Test Method

Exome Sequencing with CNV Detection
Test Code Test Copy GenesTest CPT Code Gene CPT Codes Copy CPT Codes Base Price
11537 OCA2 81479 81479,81479 $890 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
11537OCA281479 81479(x2) $890 Order Options and Pricing

Pricing Comments

Our favored testing approach is exome based NextGen sequencing with CNV analysis. This will allow cost effective reflexing to PGxome or other exome based tests. However, if full gene Sanger sequencing is desired for STAT turnaround time, insurance, or other reasons, please see link below for Test Code, pricing, and turnaround time information. If the Sanger option is selected, CNV detection may be ordered through Test #600.

An additional 25% charge will be applied to STAT orders. STAT orders are prioritized throughout the testing process.

Click here for costs to reflex to whole PGxome (if original test is on PGxome Sequencing backbone).

Click here for costs to reflex to whole PGnome (if original test is on PGnome Sequencing backbone).

The Sanger Sequencing method for this test is NY State approved.

For Sanger Sequencing click here.

Turnaround Time

18 days on average for standard orders or 13 days on average for STAT orders.

Please note: Once the testing process begins, an Estimated Report Date (ERD) range will be displayed in the portal. This is the most accurate prediction of when your report will be complete and may differ from the average TAT published on our website. About 85% of our tests will be reported within or before the ERD range. We will notify you of significant delays or holds which will impact the ERD. Learn more about turnaround times here.

Targeted Testing

For ordering sequencing of targeted known variants, go to our Targeted Variants page.

EMAIL CONTACTS

Genetic Counselors

Geneticist

  • Dana Talsness, PhD

Clinical Features and Genetics

Clinical Features

Oculocutaneous albinism (OCA) is an inherited disorder caused by deficiency in melanin synthesis that results in hypopigmentation of the skin, eyes, and hair. If the phenotype is mainly restricted to the eyes and the optic system, it is referred as ocular albinism (OA) (Gargiulo et al. 2011). The reduction or complete absence of melanin pigment in the developing eye leads to foveal hypoplasia and misrouting of the optic nerves in the affected individuals (Oetting and King 1999). The eye and optic system abnormalities that are common to all types of albinism are nystagmus, photophobia, strabismus, moderate to severe impairment of visual acuity, reduced iris pigment with iris translucency, reduced retinal pigment with visualization of the choroidal blood vessels on ophthalmoscopic examination, refractive errors and altered visual evoked potentials (VEP). The degree of skin and hair hypopigmentation varies with the type of OCA (Lewis 2012). To date, four types of non-syndromic OCA (type I-IV) have been described. Among these, OCAII (tyrosinase-positive) is the most prevalent type and twice as common as compared to OCAI in African and African-American population (Durham-Pierre et al. 1994), with estimated incidence of 1: 3,900-10,000. In the USA, estimated prevalence of OCA2 is 1:36,000 (Grønskov et al. 2007).

Genetics

OCA is genetically heterogeneous. The major autosomal recessive forms OCA I and II are caused by genetic variations in TYR and OCA2, respectively. OCA2 (previously known as P-gene) encodes the integral melanosomal membrane protein, which is hypothesized to play an essential role in maintaining the pH of the melanosomes (Brilliant 2001). The frequency of OCAII is greatly increased in patients with Angelman and Prader-willi syndromes due to the deletion of chromosome 15q (region that comprises the OCA2 gene) (Lee et al. 1994). A 2.7-kb interstitial deletion allele of the OCA2 gene (this test does not detect this deletion) accounts for 65% and 92% of mutant alleles in two African countries, Zimbabwe and Cameroon, respectively (Puri et al. 1997). So far, over 150 causative sequence variations (missense, nonsense, splicing, small and gross insertions and deletions) have been associated with OCAII (The Human Gene Mutation Database). Pathogenic sequence variations in OCA2 associated with OCAII can also be found in the Albinism Database.

Clinical Sensitivity - Sequencing with CNV PGxome

A mutational screening in 127 unrelated Chinese OCA patients identified TYR mutations in 70.1% of the patients (89/127) and OCA2 mutations in 10.2% of the patients (13 of 127) (Wei et al. 2009). Another mutation analysis in 40 Japanese albino patients reported an 8% OCA2 mutational frequency (Suzuki et al. 2003). DNA sequence analysis of thirty-six unrelated Caucasian patients diagnosed with autosomal recessive ocular albinism (AROA) revealed TYR mutations in 56% (20/36), OCA2 mutations in 8% (3/36) and both TYR and OCA2 mutations in 6% (2/36) of the patients (Hutton and Spritz 2008). Another molecular analysis of albinism in a large cohort of Italian patients identified that TYR was the most frequently mutated gene (33/45; 73.3%), followed by OCA2 (6/45; 13.3%) (Gargiulo et al. 2011).

Testing Strategy

This test provides full coverage of all coding exons of the OCA2 gene plus 10 bases of flanking noncoding DNA in all available transcripts along with other non-coding regions in which pathogenic variants have been identified at PreventionGenetics or reported elsewhere. We define full coverage as >20X NGS reads or Sanger sequencing. PGnome panels typically provide slightly increased coverage over the PGxome equivalent. PGnome sequencing panels have the added benefit of additional analysis and reporting of deep intronic regions (where applicable).

Dependent on the sequencing backbone selected for this testing, discounted reflex testing to any other similar backbone-based test is available (i.e., PGxome panel to whole PGxome; PGnome panel to whole PGnome).

This test does not detect the noncoding variant (NM_004667.4(HERC2): c.13272+874T>C), which is located in IVS86 of HERC2 and upstream of the OCA2 locus, which was reported to regulate OCA2 expression and has a high statistical association with human eye color (Iida et al. 2009).

Indications for Test

Candidates for this test are patients with symptoms consistent with OCA, family members of patients who have known mutations and carrier testing for at-risk family members. This test may also be considered for the reproductive partners of individuals who carry pathogenic variants in OCA2.

Gene

Official Gene Symbol OMIM ID
OCA2 611409
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Citations

  • Albinism Database- International Albinism Center, University of Minnesota (OCA2).
  • Brilliant MH. 2001. The mouse p (pink-eyed dilution) and human P genes, oculocutaneous albinism type 2 (OCA2), and melanosomal pH. Pigment Cell Research 14: 86–93. PubMed ID: 11310796
  • Durham-Pierre D, Gardner JM, Nakatsu Y, King RA, Francke U, Ching A, Aquaron R, Marmol V del, Brilliant MH. 1994. African origin of an intragenic deletion of the human P gene in tyrosinase positive oculocutaneous albinism. Nat. Genet. 7: 176–179. PubMed ID: 7920637
  • Gargiulo A, Testa F, Rossi S, Iorio V Di, Fecarotta S, Berardinis T de, Iovine A, Magli A, Signorini S, Fazzi E. 2011. Molecular and clinical characterization of albinism in a large cohort of Italian patients. Investigative Ophthalmology & Visual Science 52: 1281–1289. PubMed ID: 20861488
  • Grønskov K, Ek J, Brondum-Nielsen K. 2007. Oculocutaneous albinism. Orphanet Journal of Rare Diseases 2: 43. PubMed ID: 17980020
  • Hutton SM, Spritz RA. 2008. A comprehensive genetic study of autosomal recessive ocular albinism in Caucasian patients. Investigative ophthalmology & visual science 49: 868–872. PubMed ID: 18326704
  • Iida R, Ueki M, Takeshita H, Fujihara J, Nakajima T, Kominato Y, Nagao M, Yasuda T. 2009. Genotyping of five single nucleotide polymorphisms in the OCA2 and HERC2 genes associated with blue-brown eye color in the Japanese population. Cell Biochem. Funct. 27: 323–327. PubMed ID: 19472299
  • Lee ST, Nicholls RD, Bundey S, Laxova R, Musarella M, Spritz RA. 1994. Mutations of the P gene in oculocutaneous albinism, ocular albinism, and Prader-Willi syndrome plus albinism. N. Engl. J. Med. 330: 529–534. PubMed ID: 8302318
  • Lewis RA. 2012. Oculocutaneous Albinism Type 2. In: Pagon RA, Adam MP, Bird TD, Dolan CR, Fong C-T, and Stephens K, editors. GeneReviews™, Seattle (WA): University of Washington, Seattle. PubMed ID: 20301410
  • Oetting WS, King RA. 1999. Molecular basis of albinism: mutations and polymorphisms of pigmentation genes associated with albinism. Hum. Mutat. 13: 99–115. PubMed ID: 10094567
  • Puri N, Durbam-Pierre D, Aquaron R, Lund PM, King RA, Brilliant MH. 1997. Type 2 oculocutaneous albinism (OCA2) in Zimbabwe and Cameroon: distribution of the 2.7-kb deletion allele of the P gene. Hum. Genet. 100: 651–656. PubMed ID: 9341887
  • Suzuki T, Miyamura Y, Matsunaga J, Shimizu H, Kawachi Y, Ohyama N, Ishikawa O, Ishikawa T, Terao H, Tomita Y. 2003. Six novel P gene mutations and oculocutaneous albinism type 2 frequency in Japanese albino patients. Journal of investigative dermatology 120: 781–783. PubMed ID: 12713581
  • Wei A, Wang Y, Long Y, Wang Y, Guo X, Zhou Z, Zhu W, Liu J, Bian X, Lian S. 2009. A comprehensive analysis reveals mutational spectra and common alleles in Chinese patients with oculocutaneous albinism. Journal of Investigative Dermatology 130: 716–724. PubMed ID: 19865097

Ordering/Specimens

Ordering Options

We offer several options when ordering sequencing tests. For more information on these options, see our Ordering Instructions page. To view available options, click on the Order Options button within the test description.

myPrevent - Online Ordering

  • The test can be added to your online orders in the Summary and Pricing section.
  • Once the test has been added log in to myPrevent to fill out an online requisition form.
  • PGnome sequencing panels can be ordered via the myPrevent portal only at this time.

Requisition Form

  • A completed requisition form must accompany all specimens.
  • Billing information along with specimen and shipping instructions are within the requisition form.
  • All testing must be ordered by a qualified healthcare provider.

For Requisition Forms, visit our Forms page


Specimen Types

Specimen Requirements and Shipping Details

PGxome (Exome) Sequencing Panel

PGnome (Genome) Sequencing Panel

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ORDER OPTIONS

View Ordering Instructions

1) Select Test Method (Backbone)


1) Select Test Type


2) Select Additional Test Options

STAT and Prenatal Test Options are not available with Patient Plus.

No Additional Test Options are available for this test.

Note: acceptable specimen types are whole blood and DNA from whole blood only.
Total Price: $
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