title: High-resolution microarray analysis unravels complex Xq28 aberrations in patients and carriers affected by X-linked blue cone monochromacy.
abstract: The human X chromosome contains ∼ 1600 genes, about 15% of which have been associated with a specific genetic condition, mainly affecting males. Blue cone monochromacy (BCM) is an X-linked condition caused by a loss-of-function of both the OPN1LW and OPN1MW opsin genes. The cone opsin gene cluster is composed of 2-9 paralogs with 99.8% sequence homology and is susceptible to deletions, duplications, and mutations. Current diagnostic tests employ polymerase chain reaction (PCR)-based technologies; however, alterations remain undetermined in 10% of patients. Furthermore, carrier testing in females is limited or unavailable. High-resolution X chromosome-targeted CGH microarray was applied to test for rearrangements in males with BCM and female carriers from three unrelated families. Pathogenic alterations were revealed in all probands, characterized by sequencing of the breakpoint junctions and quantitative real-time PCR. In two families, we identified a novel founder mutation that consisted of a complex 3-kb deletion that embraced the cis-regulatory locus control region and insertion of an additional aberrant OPN1MW gene. The application of high-resolution X-chromosome microarray in clinical diagnosis brings significant advantages in detection of small aberrations that are beyond the resolution of clinically available aCGH analysis and which can improve molecular diagnosis of the known conditions and unravel previously unrecognized X-linked diseases.
authors.affiliation: Pittsburgh Cytogenetics Laboratory, Center for Medical Genetics and Genomics, Magee-Womens Hospital of UPMC, Pittsburgh, PA, USA.|Department of Obstetrics, Gynecology and Reproductive Sciences, Pittsburgh, PA, USA.|Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
authors.forename: S A
authors.initials: SA
authors.lastname: Yatsenko
authors.affiliation: Pittsburgh Cytogenetics Laboratory, Center for Medical Genetics and Genomics, Magee-Womens Hospital of UPMC, Pittsburgh, PA, USA.
authors.forename: H A
authors.initials: HA
authors.lastname: Bakos
authors.affiliation: Pittsburgh Cytogenetics Laboratory, Center for Medical Genetics and Genomics, Magee-Womens Hospital of UPMC, Pittsburgh, PA, USA.
authors.forename: K
authors.initials: K
authors.lastname: Vitullo
authors.affiliation: Department of Ophthalmology, Hamilton Eye Institute, University of Tennessee Health Science Center, Memphis, TN, USA.
authors.forename: M
authors.initials: M
authors.lastname: Kedrov
authors.affiliation: Department of Obstetrics, Gynecology and Reproductive Sciences, Pittsburgh, PA, USA.
authors.forename: A
authors.initials: A
authors.lastname: Kishore
authors.affiliation: Department of Ophthalmology, Hamilton Eye Institute, University of Tennessee Health Science Center, Memphis, TN, USA.
authors.forename: B J
authors.initials: BJ
authors.lastname: Jennings
authors.affiliation: Pittsburgh Cytogenetics Laboratory, Center for Medical Genetics and Genomics, Magee-Womens Hospital of UPMC, Pittsburgh, PA, USA.|Department of Obstetrics, Gynecology and Reproductive Sciences, Pittsburgh, PA, USA.|Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.|Department of Human Genetics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA.
authors.forename: U
authors.initials: U
authors.lastname: Surti
authors.affiliation: Department of Obstetrics, Gynecology and Reproductive Sciences, Pittsburgh, PA, USA.
authors.forename: M A
authors.initials: MA
authors.lastname: Wood-Trageser
authors.affiliation: Department of Obstetrics, Gynecology and Reproductive Sciences, Pittsburgh, PA, USA.
authors.forename: S
authors.initials: S
authors.lastname: Cercone
authors.affiliation: Department of Obstetrics, Gynecology and Reproductive Sciences, Pittsburgh, PA, USA.|Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
authors.forename: A N
authors.initials: AN
authors.lastname: Yatsenko
authors.affiliation: Pittsburgh Cytogenetics Laboratory, Center for Medical Genetics and Genomics, Magee-Womens Hospital of UPMC, Pittsburgh, PA, USA.|Department of Obstetrics, Gynecology and Reproductive Sciences, Pittsburgh, PA, USA.|Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.|Department of Human Genetics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA.
authors.forename: A
authors.initials: A
authors.lastname: Rajkovic
authors.affiliation: Department of Ophthalmology, Hamilton Eye Institute, University of Tennessee Health Science Center, Memphis, TN, USA.
authors.forename: A
authors.initials: A
authors.lastname: Iannaccone
mesh_terms: D002869:Chromosome Aberrations; D056905:Chromosome Breakpoints; D002872:Chromosome Deletion; D041321:Chromosomes, Human, X; D003117:Color Vision Defects / Q000175:diagnosis* / Q000235:genetics*; D055028:Comparative Genomic Hybridization; D003241:Consanguinity; D023061:Gene Order; D040181:Genetic Diseases, X-Linked; D006579:Heterozygote; D006801:Humans; D008297:Male; D020411:Oligonucleotide Array Sequence Analysis; D010375:Pedigree
keywords: X chromosome; X-linked disease; Xq28 deletion; aCGH; blue cone monochromacy; color vision