Identification of three novel OA1 gene mutations identified in three families misdiagnosed with congenital nystagmus and carrier status determination by real-time quantitative PCR assay

We identified three previously undescribed mutations consisting of two intragenic deletions (one encompassing exon 6, the other encompassing exons 7–8), and a point mutation (310delG) in exon 2. We report the development of a new method for diagnosis of heterozygous deletions in OA1 gene based on measurement of gene copy number using real-time quantitative PCR from genomic DNA.The identification of OA1 mutations in families earlier reported as families with hereditary nystagmus indicate that ocular albinism type 1 is probably underdiagnosed. Our method of real-time quantitative PCR of OA1 exons with DMD exon as external standard performed on the LightCycler？ allows quick and accurate carrier-status assessment for at-risk females.Congenital nystagmus (CN) is the common symptom of a range of diseases involving the macula from infancy on, and includs at least three X-linked disorders: Nettleship-Falls ocular albinism type 1 (OA1; MIM#300500) mapped to Xp22.3, complete congenital stationary night blindness (CSNB1; MIM#310500), mapped to Xp11.3 and blue-cone monochromatism (CBBM; MIM#303700), mapped to Xq28. These genetic disorders must be distinguished from the congenital motor nystagmus (CMN), a hereditary disorder characterized by bilateral ocular oscillations which occurs in the absence of any apparent ocular disease [1]. Diagnosis of the underlying disease often requires extensive clinical and electrophysiological examinations. Prevalence of OA1 is estimated around 1 in 50,000 live births in Caucasian populations. The most frequent findings in hemizygous individuals with OA1 are foveal hypoplasia, hypopigmentation of the retina and iris translucency together with normally pigmented skin and hair [2]. The disease typically results in severely impaired visual acuity in affected males who also manifest variable strabismus, photophobia, and misrouting of optic pathway. The size, shape and number of melanocytes are normal in the skin, hair follicle and retinal pigment ep