Diagnostic DNA testing for X-linked ocular albinism (OA1) with a hierarchical mutation screening protocol

M. Hegde, R. A. Lewis, Carolyn (Sue) Richards

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

Albinism is a group of inherited conditions in which affected individuals 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 at 1 in 20,000, based on poor epidemiological data. X-linked Nettleship-Falls ocular albinism (XLOA, OA1) affects ∼ 1/150,000 males in the population. XLOA effects reduce visual acuity and nystagmus, result in a mild skin and hair phenotype, and occur mostly in XY males. Female carriers of XLOA have normal visual acuity, but often show iris punctate transillumination and a classic pattern of mosaic retinal pigmentation, coarse and grainy in the macula and becoming increasingly reticular into the periphery of the retinal pigment epithelium. Studies of OA1 have shown linkage of a single gene to markers at Xp22.3-p22.2. About 48% of the reported mutations in the OA1 gene are intragenic deletions and about 43% are point mutations. We present a hierarchical strategy for mutation screening for diagnostic testing for OA1 that comprises two tiers: first, multiplex PCR to detect intragenic deletions in the OA1 gene with denaturing high-performance liquid chromatography (dHPLC, and, second, heteroduplex analysis with dHPLC to scan for mutations, with subsequent sequencing of variants to confirm putative mutations in the OA1 gene. Prenatal diagnosis can be provided for families when the mutation has been firmly identified. We have validated this procedure with positive controls that were identified in patients by Southern blot, single-stranded conformation polymorphism (SSCP), and sequencing. In this hierarchical strategy, these procedures have an analytical sensitivity of gt;99%.

Original languageEnglish (US)
Pages (from-to)7-14
Number of pages8
JournalGenetic Testing
Volume6
Issue number1
DOIs
StatePublished - 2002
Externally publishedYes

Fingerprint

Ocular Albinism
Mutation
Albinism
DNA
Hair
Visual Acuity
Heteroduplex Analysis
Transillumination
Genes
Skin
Retinal Pigment Epithelium
Multiplex Polymerase Chain Reaction
Gene Deletion
Pigmentation
Iris
Southern Blotting
Prenatal Diagnosis
Point Mutation
High Pressure Liquid Chromatography
Phenotype

ASJC Scopus subject areas

  • Genetics(clinical)

Cite this

Diagnostic DNA testing for X-linked ocular albinism (OA1) with a hierarchical mutation screening protocol. / Hegde, M.; Lewis, R. A.; Richards, Carolyn (Sue).

In: Genetic Testing, Vol. 6, No. 1, 2002, p. 7-14.

Research output: Contribution to journalArticle

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