GENETIC SCREENING SERVICE FOR AMERICAN FAMILIES

Reasons for Referral
Methodology
Price
Specimen Requirements
Contact Information

X-Linked Ocular Albinism
Baylor College of Medicine • Diagnostic Sequencing Laboratory

Albinism refers to a group of inherited conditions in which the affected people have less than normal pigment in the eyes, skin, and hair compared to others of the same race and ethnic background. The prevalence of all types of albinism in the United States is estimated, on the basis of poor epidemiologic data, at 1 in 20,000. The parents of most children with Albinism have normal hair and eye color for their ethnic background and have no family history of Albinism. For historical convenience, Albinism has been divided into two clinical groups, namely, Oculocutaneous Albinism and so called ‘Ocular Albinism’.

Historically, Ocular Albinism involves the eyes only, although in reality that is rarely true. However, the cutaneous features may be subtle, unless one looks carefully at siblings in the same family at comparable ages. X-linked Nettleship-Falls Ocular Albinism (XLOA) affects ~ 1/150,000 males in the general population. XLOA results in reduced visual acuity and occurs primarily in XY males. Skin and hair color is usually normal or slightly lighter than those of other family members. These males also have infantile nystagmus, photophobia, and various forms of strabismus. Some males may have hypopigmented macules or a mild generalized reduction in pigment in the skin when compared to other family members. A rare form of autosomal recessive ‘Ocular Albinism’ also exists.

Female carriers of XLOA usually have normal vision but usually show a classic mosaic pattern of retinal pigmentation [when the pupil is dilated and the retina examined carefully, especially outside the major macular vascular arcade], becoming progressively more coarse and reticular in the retinal periphery, and often punctate iris illumination at a slitlamp biomicroscopic examination by an informed ophthalmologist.

Studies of XLOA have shown linkage of a single gene to markers in Xp22.3-p22.2. The OA1 gene product is a membrane protein, which is essential for the formation and/or maturation of melanosomes. Molecular genetic testing for X-linked Ocular Albinism is available at the Baylor Diagnostic Sequencing Laboratory. Testing has been divided in two tiers. In the North American population, approximately 48% of the mutations in OA1 gene have been reported to be intragenic deletions and the up to 43% to be point mutations. Symptomatic males will be tested using a multiplex PCR based assay for all nine exons of the gene to detect intragenic deletions as a first tier of testing. The second tier screening involves the amplifications of all the exons individually and screening them for point mutations and deletions on dHPLC. The variants identified on dHPLC will be subsequently sequenced in both directions for mutation/ polymorphism identification.

REASONS FOR REFERRAL

Confirmation of clinical diagnosis of X-Linked Ocular Albinism (XLOA) for individuals with phenotypic features Carrier testing in females with a definite family history of XLOA (in conjunction with careful opthalmological examination) Prenatal diagnosis in families with an identified mutation in the OA1 gene.

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METHODOLOGY

Patient DNA samples will undergo amplification of all 9 exons of the OA1 gene individually and in a multiplex format. The multiplexed PCR products are electrophoresed to detect exon deletions. The individual amplified products are scanned for point mutations and deletions using dHPLC (Denaturing high performance liquid chromatography). Amplicons showing variations are subsequently sequenced for mutation/polymorphism confirmation. dHPLC has an analytical sensitivity of >99%. In the absence of a male proband, carrier testing on high-risk females can be performed by denaturing high performance liquid chromatography (DHPLC) analysis that has a lower estimated detection rate.

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PRICE

Direct Billing Third Party Billing CPT Codes
Index Case $600 per sample $700 per sample 83891, 83901, 83898x9, 83903 x9, 83904 x2, 83912 Additional Family Members $300 per sample $350 per sample 83891, 83901, 83898, 83903, 83904 x2, 83912 Known familial mutation only

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CLINICAL SENSITIVITY 75%

SPECIMEN REQUIREMENTS

Blood: EDTA (purple-top) tubes: Adult/Child: Minimum 6-14 cc

Prenatal sample: 10-20mg CVS/ 20ml Amniotic fluid or two T-25 flasks

Requisition form must accompany the specimen. Prior to any genetic testing, we recommend genetic counseling and we request that the subject sign our consent statement and submit it with the sample. To receive forms, additional information or specimen collection kits, please contact the laboratory. For information about prenatal testing, please contact our laboratory. Additional charges may apply for prenatal samples.

REFERENCES

1. Bassi et al, Hum Genet, 2001, 108: 51-54 2.Schnur et al, Am J Hum Genet, 1998, 62:800-809 3. Schiaffino et al, Hum Mol Gen, 1995, 4(12), 2319-2325

CONTACT INFORMATION

Director: Carolyn Sue Richards, Ph.D. F.A.C.M.G.
Postdoctoral Fellow: Madhuri Hegde, Ph.D.
Email: mhegde@bcm.tmc.edu
One Baylor Plaza, Room T528
Houston, Texas 77030
Email: dsl@bcm.tmc.edu
Phone: 800-411-GENE (4363) or 713-798-1858
Fax: 713-798-6182
Website: www.bcmgeneticlabs.org

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