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Xinjing Wang, Jackson Gao, Keith Wetherby, CHIMERE ROBERSON, MELISSA REEVES, ALEXANDRA GARAFALO, REBECCA PARRISH, ANNETTE YIM; Segregation analysis revealed causative mutations in an Oculocutaneous Albinism (OCA) patient. Invest. Ophthalmol. Vis. Sci. 2016;57(12):6581.
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© ARVO (1962-2015); The Authors (2016-present)
Oculocutaneous albinism is composed of autosomal recessive disorders of melanin biosynthesis characterized by hypopigmentation of hair, skin and eyes. OCA causative mutations have been found in several responsible genes. We here analyzed our OCA patients for an OCA2 gene exon 7 deletion to evaluate the frequency of this deletion in our patient population.
We studied 100 patients referred with the clinical diagnosis of OCA. Total genomic DNA was extracted from blood samples obtained from OCA patients. The DNA was first screened for mutations in the TYR gene and/or OCA2 gene by direct sequencing. In addition, we performed OCA 2 gene exon 7 deletion studies using the long range PCR kit developed by Takara.
In the patients without two mutations or two mutation candidates in either TYR gene or OCA2 gene, we analyzed their DNA for the potential exon 7 deletion. We found none of these patients bearing the common exon 7 deletion. However, we found a patient with one known OCA2 gene mutation, and one variant with unknown significant but likely pathogenic, p.R305W, also carrying the exon 7 deletion in heterozygosity. Moreover, we found that his mom is positive for the p.R305W in a homozygous status and the exon 7 deletion in a heterozygous status. We excluded another four OCA patients who bear the p.R305W from possibly carrying the exon 7 deletion.
Our analyses provide genetic evidence and molecular conformation for the causative mutations in this cohort of OCA patients. For the patients without a second mutation, we explored the likelihood of the most common exonic deletion, the 2.7 kb exon 7 deletion, in the OCA2 gene for the genotype-phenotype correlation. For the controversial variant, p.R305W, we suggest an unlikely pathogenic status for molecular diagnosis.
This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.
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