The Experts below are selected from a list of 321 Experts worldwide ranked by ideXlab platform
Mika Nakajima - One of the best experts on this subject based on the ideXlab platform.
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ngs based targeted resequencing identified rare subtypes of Albinism providing accurate molecular diagnosis for japanese patients with Albinism
Pigment Cell & Melanoma Research, 2019Co-Authors: Ken Okamura, Masahiro Hayashi, Yuko Abe, Michihiro Kono, Kimiko Nakajima, Yumi Aoyama, Chikako Nishigori, Hiroshi Ishimoto, Yuji Ishimatsu, Mika NakajimaAbstract:Albinism, which is commonly inherited as an autosomal recessive trait, is characterized by a reduction or absence of melanin in the eyes, skin, and hair. To date, more than 20 causal genes for Albinism have been identified; thus, the accurate diagnosis of Albinism requires next-generation sequencing (NGS). In this study, we analyzed 46 patients who tested negative for oculocutaneous Albinism (OCA)1-4 and Hermansky-Pudlak syndrome (HPS)1 based on conventional analysis, in addition to 28 new Japanese patients, using NGS-based targeted resequencing. We identified a genetic background for Albinism in 18 of the 46 patients (39%), who were previously tested negative according to the conventional analysis. In addition, we unveiled a genetic predisposition toward Albinism in 23 of the 28 new patients (82%). We identified six patients with rare subtypes of Albinism, including HPS3, HPS4, and HPS6, and found 12 novel pathological mutations in Albinism-related genes. Furthermore, most patients who were not diagnosed with Albinism by the NGS analysis showed mild manifestations of Albinism without apparent eye symptoms and harbored only one heterozygous mutation, occasionally in combination with skin-color associated gene variants.
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NGS‐based targeted resequencing identified rare subtypes of Albinism: Providing accurate molecular diagnosis for Japanese patients with Albinism
Pigment Cell & Melanoma Research, 2019Co-Authors: Ken Okamura, Masahiro Hayashi, Yuko Abe, Michihiro Kono, Kimiko Nakajima, Yumi Aoyama, Chikako Nishigori, Hiroshi Ishimoto, Yuji Ishimatsu, Mika NakajimaAbstract:Albinism, which is commonly inherited as an autosomal recessive trait, is characterized by a reduction or absence of melanin in the eyes, skin, and hair. To date, more than 20 causal genes for Albinism have been identified; thus, the accurate diagnosis of Albinism requires next-generation sequencing (NGS). In this study, we analyzed 46 patients who tested negative for oculocutaneous Albinism (OCA)1-4 and Hermansky-Pudlak syndrome (HPS)1 based on conventional analysis, in addition to 28 new Japanese patients, using NGS-based targeted resequencing. We identified a genetic background for Albinism in 18 of the 46 patients (39%), who were previously tested negative according to the conventional analysis. In addition, we unveiled a genetic predisposition toward Albinism in 23 of the 28 new patients (82%). We identified six patients with rare subtypes of Albinism, including HPS3, HPS4, and HPS6, and found 12 novel pathological mutations in Albinism-related genes. Furthermore, most patients who were not diagnosed with Albinism by the NGS analysis showed mild manifestations of Albinism without apparent eye symptoms and harbored only one heterozygous mutation, occasionally in combination with skin-color associated gene variants.
Richard A King - One of the best experts on this subject based on the ideXlab platform.
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posterior staphyloma in oculocutaneous Albinism another possible cause of reduced visual acuity
Journal of Aapos, 2015Co-Authors: Lisa A Schimmenti, Murray H Brilliant, Richard A King, Cheri Schoonveld, Jennifer L. Anderson, Gail C SummersAbstract:Posterior staphyloma is typically associated with myopic degeneration and has not been recognized as a cause of reduced visual acuity in Albinism. We report 3 cases of posterior staphyloma, each with oculocutaneous Albinism (OCA) defined by phenotype and genotype. Two cases are biological sisters with OCA type 2; one was myopic and the other was hyperopic. The third case involves a man with OCA associated with Hermansky-Pudlak syndrome (HPS-5). Staphyloma may be another cause of reduced visual acuity in Albinism, particularly with increasing age. It may occur in association with myopia or hyperopia.
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the r402q tyrosinase variant does not cause autosomal recessive ocular Albinism
American Journal of Medical Genetics Part A, 2009Co-Authors: William S. Oetting, Gail C Summers, James P. Fryer, Jacy Pietsch, Marcia J Brott, Sarah Savage, Richard A KingAbstract:Mutations in the gene for tyrosinase, the key enzyme in melanin synthesis, are responsible for oculocutaneous Albinism type 1, and more than 100 mutations of this gene have been identified. The c.1205G > A variant of the tyrosinase gene (rs1126809) predicts p.R402Q and expression studies show thermolabile enzyme activity for the variant protein. The Q402 allele has been associated with autosomal recessive ocular Albinism when it is in trans with a tyrosinase gene mutation associated with oculocutaneous Albinism type 1. We have identified 12 families with oculocutaneous Albinism type 1 that exhibit segregation of the c.1205G > A variant with a known pathologic mutation on the homologous chromosome, and demonstrate no genetic association between autosomal recessive oculocutaneous Albinism and the Q402 variant. We conclude that the codon 402 variant of the tyrosinase gene is not associated with Albinism.
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Segregation analysis of brown oculocutaneous Albinism.
Clinical Genetics, 2008Co-Authors: Richard A King, Stephen S. RichAbstract:The segregation of brown (type IV) oculocutaneous Albinism was analyzed in 18 Nigerian families. Analysis using the POINTER program showed that this type of oculocutaneous Albinism was inherited in an autosomal recessive pattern, with an estimated gene frequency of 0.025 +/- 0.007 in this population. The enzyme defect responsible for brown oculocutaneous Albinism is unknown.
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Management of Genetic Syndromes - Albinism and Hermansky‐Pudlak Syndrome
Management of Genetic Syndromes, 2005Co-Authors: Richard A King, C. Gail SummersAbstract:The term Albinism refers to a group of congenital genetic abnormalities resulting from an inability of the pigment cell (melanocyte) to synthesize normal amounts of melanin pigment and is produced by mutations in at least 12 genes. Reduced melanin synthesis in the melanocytes of the skin, hair, and eyes produces oculocutaneous Albinism, while a reduction primarily involving the retinal pigment epithelium produces ocular Albinism. Hermansky-Pudlak syndrome includes the triad of oculocutaneous Albinism, a mild bleeding diathesis, and a ceroid storage disease affecting primarily the lungs and the gut. Oculocutaneous Albinism is the most common inherited disorder of generalized hypopigmentation, with an estimated frequency of 1 in 20,000 in most populations. It has been described in all ethnic groups and in all animal species making it one of the most widely distributed genetic abnormalities in the animal kingdom. Ocular Albinism is less common with an estimated frequency of 1 in 50,000 to 1 in 60,000. It is X-linked. Hermansky-Pudlak syndrome is a rare condition in most populations. In the Puerto Rican population, however, two forms are found with type 1 having an estimated frequency of approximately 1 in 1800. Keywords: Albinism; oculocutaneous Albinism; ocular Albinism; melanin; melanocytes; Hermansky-Pudlak syndrome; hypopigmentation; tyrosinase
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Positive angle kappa in Albinism
Journal of Aapos, 2004Co-Authors: Kimberly Merrill, Richard A King, Jane D. Lavoie, C. Gail SummersAbstract:Abstract Background Albinism is an inherited disorder of deficient melanin production. There is a high prevalence of strabismus in patients with Albinism. We investigated the prevalence of a positive angle kappa in patients with Albinism and report its effect on assessment of binocular alignment. Methods We retrospectively reviewed the charts of 207 consecutive patients with the diagnosis of Albinism seen at the University of Minnesota between 1984 and 2002. Angle kappa and alignment using prism and alternate-cover test (PACT) and Krimsky measurements were recorded. Results In 99.6% of our patients with Albinism, angle kappa was noted to be positive. The mean difference between PACT and Krimsky measurements was 17.11 prism diopters in the more exotropic (or less esotropic) direction per Krimsky test. Because of the high prevalence of a positive angle kappa, esodeviations often appeared less and exodeviations appeared greater than when measured using PACT. Conclusions Positive angle kappa can be considered another clinical feature of Albinism. Consideration should be given to the effect of positive angle kappa on alignment as observed by Krimsky measurement when planning extraocular muscle surgery, particularly when preoperative sensory testing suggests binocular potential.
Ken Okamura - One of the best experts on this subject based on the ideXlab platform.
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ngs based targeted resequencing identified rare subtypes of Albinism providing accurate molecular diagnosis for japanese patients with Albinism
Pigment Cell & Melanoma Research, 2019Co-Authors: Ken Okamura, Masahiro Hayashi, Yuko Abe, Michihiro Kono, Kimiko Nakajima, Yumi Aoyama, Chikako Nishigori, Hiroshi Ishimoto, Yuji Ishimatsu, Mika NakajimaAbstract:Albinism, which is commonly inherited as an autosomal recessive trait, is characterized by a reduction or absence of melanin in the eyes, skin, and hair. To date, more than 20 causal genes for Albinism have been identified; thus, the accurate diagnosis of Albinism requires next-generation sequencing (NGS). In this study, we analyzed 46 patients who tested negative for oculocutaneous Albinism (OCA)1-4 and Hermansky-Pudlak syndrome (HPS)1 based on conventional analysis, in addition to 28 new Japanese patients, using NGS-based targeted resequencing. We identified a genetic background for Albinism in 18 of the 46 patients (39%), who were previously tested negative according to the conventional analysis. In addition, we unveiled a genetic predisposition toward Albinism in 23 of the 28 new patients (82%). We identified six patients with rare subtypes of Albinism, including HPS3, HPS4, and HPS6, and found 12 novel pathological mutations in Albinism-related genes. Furthermore, most patients who were not diagnosed with Albinism by the NGS analysis showed mild manifestations of Albinism without apparent eye symptoms and harbored only one heterozygous mutation, occasionally in combination with skin-color associated gene variants.
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NGS‐based targeted resequencing identified rare subtypes of Albinism: Providing accurate molecular diagnosis for Japanese patients with Albinism
Pigment Cell & Melanoma Research, 2019Co-Authors: Ken Okamura, Masahiro Hayashi, Yuko Abe, Michihiro Kono, Kimiko Nakajima, Yumi Aoyama, Chikako Nishigori, Hiroshi Ishimoto, Yuji Ishimatsu, Mika NakajimaAbstract:Albinism, which is commonly inherited as an autosomal recessive trait, is characterized by a reduction or absence of melanin in the eyes, skin, and hair. To date, more than 20 causal genes for Albinism have been identified; thus, the accurate diagnosis of Albinism requires next-generation sequencing (NGS). In this study, we analyzed 46 patients who tested negative for oculocutaneous Albinism (OCA)1-4 and Hermansky-Pudlak syndrome (HPS)1 based on conventional analysis, in addition to 28 new Japanese patients, using NGS-based targeted resequencing. We identified a genetic background for Albinism in 18 of the 46 patients (39%), who were previously tested negative according to the conventional analysis. In addition, we unveiled a genetic predisposition toward Albinism in 23 of the 28 new patients (82%). We identified six patients with rare subtypes of Albinism, including HPS3, HPS4, and HPS6, and found 12 novel pathological mutations in Albinism-related genes. Furthermore, most patients who were not diagnosed with Albinism by the NGS analysis showed mild manifestations of Albinism without apparent eye symptoms and harbored only one heterozygous mutation, occasionally in combination with skin-color associated gene variants.
Gail C Summers - One of the best experts on this subject based on the ideXlab platform.
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assessing ganglion cell layer topography in human Albinism using optical coherence tomography
Investigative Ophthalmology & Visual Science, 2020Co-Authors: Erica N Woertz, Gail C Summers, Bisola S Omoba, Taylor M Dunn, Stephanie J Chiu, Sina Farsiu, Sasha Strul, Arlene V Drack, Joseph CarrollAbstract:Purpose To test whether ganglion cell layer (GCL) and inner plexiform layer (IPL) topography is altered in Albinism. Methods Optical coherence tomography scans were analyzed in 30 participants with Albinism and 25 control participants. Horizontal and vertical line scans were acquired at the fovea, then strip registered and averaged. The Duke Optical Coherence Tomography Retinal Analysis Program was used to automatically segment the combined GCL and IPL and total retinal thickness, followed by program-assisted manual segmentation of the boundary between the GCL and IPL. Layer thickness and area under the curve (AUC) were calculated within 2.5 mm of the fovea. Nasal-temporal and superior-inferior asymmetry were calculated as an AUC ratio in each quadrant. Results GCL and IPL topography varied between participants. The summed AUC in all quadrants was similar between groups for both the GCL (P = 0.84) and IPL (P = 0.08). Both groups showed nasal-temporal asymmetry in the GCL, but only participants with Albinism had nasal-temporal asymmetry in the IPL. Nasal-temporal asymmetry was greater in Albinism for both the GCL (P < 0.0001) and the IPL (P = 0.0006). The GCL usually comprised a greater percentage of the combined GCL and IPL in controls than in Albinism. Conclusions The GCL and IPL have greater structural variability than previously reported. GCL and IPL topography are significantly altered in Albinism, which suggests differences in the spatial distribution of retinal ganglion cells. This finding provides insight into foveal development and structure-function relationships in foveal hypoplasia.
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the henle fiber layer in Albinism comparison to normal and relationship to outer nuclear layer thickness and foveal cone density
Investigative Ophthalmology & Visual Science, 2018Co-Authors: Daniel J Lee, Erica N Woertz, Melissa A. Wilk, Gail C Summers, Alexis Visotcky, Heather Heitkotter, Rachel E Linderman, Sergey Tarima, Brian P Brooks, Murray H BrilliantAbstract:Purpose Directional optical coherence tomography (D-OCT) allows the visualization of the Henle fiber layer (HFL) in vivo. Here, we used D-OCT to characterize the HFL and outer nuclear layer (ONL) in Albinism and examine the relationship between true foveal ONL and peak cone density. Methods Horizontal D-OCT B-scans were acquired, registered, and averaged for 12 subjects with oculocutaneous Albinism and 26 control subjects. Averaged images were manually segmented to extract HFL and ONL thickness. Adaptive optics scanning light ophthalmoscopy was used to acquire images of the foveal cone mosaic in 10 subjects with Albinism, from which peak cone density was assessed. Results Across the foveal region, the HFL topography was different between subjects with Albinism and normal controls. In particular, foveal HFL thickness was thicker in Albinism than in normal controls (P < 0.0001), whereas foveal ONL thickness was thinner in Albinism than in normal controls (P < 0.0001). The total HFL and ONL thickness was not significantly different between Albinism and controls (P = 0.3169). Foveal ONL thickness was positively correlated with peak cone density in subjects with Albinism (r = 0.8061, P = 0.0072). Conclusions Foveal HFL and ONL topography are significantly altered in Albinism relative to normal controls. Our data suggest that increased foveal cone packing drives the formation of Henle fibers, more so than the lateral displacement of inner retinal neurons (which is reduced in Albinism). The ability to quantify foveal ONL and HFL may help further stratify grading schemes used to assess foveal hypoplasia.
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a cross sectional examination of visual acuity by specific type of Albinism
Journal of Aapos, 2016Co-Authors: Caitlin Nosanov Winsor, John E. Connett, Ann M. Holleschau, Gail C SummersAbstract:Purpose Reports of best-corrected visual acuity (BCVA) in Albinism are often based on overlapping clinical phenotypes. BCVA in Albinism has been shown to improve with age. This study reports a large cross-sectional investigation to determine whether BCVA differs by specific type of Albinism when age-corrected. Methods This retrospective review identified 170 individuals with a specific type of Albinism identified by mutation(s) in a gene known to cause Albinism (for OCA1, OCA2, and Hermansky-Pudlak syndrome ([HPS]) or a specific phenotype (white hair and no melanin pigment in OCA1A; pigmentary mosaicism in the obligate carriers for males with OA1). We recorded optotype binocular BCVA at final follow-up. Patients were age-grouped (2-5 years, 6-14 years, and ≥15 years) for comparison. Results The greatest visual acuity deficit was found for OCA1A in all age groups. At age ≥15 years (n = 79), mean BCVA was 20/128 for OCA1A, 20/37 for OCA1B, 20/59 for OCA2, 20/63 for OA1, and 20/121 for HPS. Significant differences between BCVA at ≥15 years were found in the following: OCA1A vs OCA1B, OCA1A vs OCA2, OCA1A vs OA1, OCA1B vs HPS, OCA2 vs HPS, and OA1 vs HPS (P ≤ 0.02). Conclusions This study provides a large sample size and includes only those with a specific type of Albinism. BCVA varies by Albinism type, and there is overlap in BCVA, particularly in the younger age groups. For ages ≥15 years, there are significant differences in BCVA between several types of Albinism.
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posterior staphyloma in oculocutaneous Albinism another possible cause of reduced visual acuity
Journal of Aapos, 2015Co-Authors: Lisa A Schimmenti, Murray H Brilliant, Richard A King, Cheri Schoonveld, Jennifer L. Anderson, Gail C SummersAbstract:Posterior staphyloma is typically associated with myopic degeneration and has not been recognized as a cause of reduced visual acuity in Albinism. We report 3 cases of posterior staphyloma, each with oculocutaneous Albinism (OCA) defined by phenotype and genotype. Two cases are biological sisters with OCA type 2; one was myopic and the other was hyperopic. The third case involves a man with OCA associated with Hermansky-Pudlak syndrome (HPS-5). Staphyloma may be another cause of reduced visual acuity in Albinism, particularly with increasing age. It may occur in association with myopia or hyperopia.
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clinical insights into foveal morphology in Albinism
Journal of Pediatric Ophthalmology & Strabismus, 2015Co-Authors: Brandon K. Mccafferty, Melissa A. Wilk, Murray H Brilliant, Joseph Carroll, Jennifer L. Anderson, John T Mcallister, Adam M Dubis, Kimberly E Stepien, Gail C SummersAbstract:PURPOSE A hallmark of Albinism is foveal hypoplasia. However, literature suggests variable foveal development. This study evaluates the association between ocular phenotype and foveal morphology to demonstrate the broad structural and functional spectrum. METHODS Best-corrected visual acuity (BCVA), nystagmus, angle kappa, stereoacuity, iris transillumination, macular melanin presence, foveal avascular zone, and annular reflex were recorded in 14 patients with Albinism. Spectral-domain optical coherence tomography provided macular images. RESULTS The clinical phenotype was broad, with BCVA varying from 20/20 to 20/100. Better BCVA was associated with a preserved foveal avascular zone, annular macular reflex, stereoacuity, and macular melanin. Imaging demonstrated a continuum of foveal development correlating with BCVA. Individuals with a rudimentary pit had normal inner and outer segment lengthening and better BCVA. CONCLUSIONS The spectrum of ocular structure and visual function in Albinism is broad, suggesting a possible diagnosis of Albinism in a patient with an even more normal clinical presentation.
Melissa A. Wilk - One of the best experts on this subject based on the ideXlab platform.
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the relationship between retinal cone density and cortical magnification in human Albinism
Journal of Vision, 2020Co-Authors: Erica N Woertz, Ethan Duwell, Jedidiah Mathis, Melissa A. Wilk, Joseph Carroll, Edgar A DeyoeAbstract:The human fovea lies at the center of the retina and supports high-acuity vision. In normal visual system development, the highest acuity is correlated with both a high density of cone photoreceptors in the fovea and a magnified retinotopic representation of the fovea in the visual cortex. Both cone density and the cortical area dedicated to each degree of visual space-the latter describing cortical magnification (CM)-steadily decrease with increasing eccentricity from the fovea. In Albinism, peak cone density at the fovea and visual acuity are decreased, but seem to be within normal limits in the periphery, thus providing a model to explore the correlation between retinal structure, cortical structure, and behavior. Here, we used adaptive optics scanning light ophthalmoscopy to assess retinal cone density and functional magnetic resonance imaging to measure CM in the primary visual cortex of normal controls and individuals with Albinism. We find that retinotopic organization is more varied among individuals with Albinism than previously appreciated. Additionally, CM outside the fovea is similar to that in controls, but also more variable. CM in Albinism and controls exceeds that which might be predicted based on cone density alone, but is more accurately predicted by retinal ganglion cell density. This finding suggests that decreased foveal cone density in Albinism may be partially counteracted by nonuniform connectivity between cones and their downstream signaling partners. Together, these results emphasize that central as well as retinal factors must be included to provide a complete picture of aberrant structure and function in Albinism.
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the henle fiber layer in Albinism comparison to normal and relationship to outer nuclear layer thickness and foveal cone density
Investigative Ophthalmology & Visual Science, 2018Co-Authors: Daniel J Lee, Erica N Woertz, Melissa A. Wilk, Gail C Summers, Alexis Visotcky, Heather Heitkotter, Rachel E Linderman, Sergey Tarima, Brian P Brooks, Murray H BrilliantAbstract:Purpose Directional optical coherence tomography (D-OCT) allows the visualization of the Henle fiber layer (HFL) in vivo. Here, we used D-OCT to characterize the HFL and outer nuclear layer (ONL) in Albinism and examine the relationship between true foveal ONL and peak cone density. Methods Horizontal D-OCT B-scans were acquired, registered, and averaged for 12 subjects with oculocutaneous Albinism and 26 control subjects. Averaged images were manually segmented to extract HFL and ONL thickness. Adaptive optics scanning light ophthalmoscopy was used to acquire images of the foveal cone mosaic in 10 subjects with Albinism, from which peak cone density was assessed. Results Across the foveal region, the HFL topography was different between subjects with Albinism and normal controls. In particular, foveal HFL thickness was thicker in Albinism than in normal controls (P < 0.0001), whereas foveal ONL thickness was thinner in Albinism than in normal controls (P < 0.0001). The total HFL and ONL thickness was not significantly different between Albinism and controls (P = 0.3169). Foveal ONL thickness was positively correlated with peak cone density in subjects with Albinism (r = 0.8061, P = 0.0072). Conclusions Foveal HFL and ONL topography are significantly altered in Albinism relative to normal controls. Our data suggest that increased foveal cone packing drives the formation of Henle fibers, more so than the lateral displacement of inner retinal neurons (which is reduced in Albinism). The ability to quantify foveal ONL and HFL may help further stratify grading schemes used to assess foveal hypoplasia.
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clinical insights into foveal morphology in Albinism
Journal of Pediatric Ophthalmology & Strabismus, 2015Co-Authors: Brandon K. Mccafferty, Melissa A. Wilk, Murray H Brilliant, Joseph Carroll, Jennifer L. Anderson, John T Mcallister, Adam M Dubis, Kimberly E Stepien, Gail C SummersAbstract:PURPOSE A hallmark of Albinism is foveal hypoplasia. However, literature suggests variable foveal development. This study evaluates the association between ocular phenotype and foveal morphology to demonstrate the broad structural and functional spectrum. METHODS Best-corrected visual acuity (BCVA), nystagmus, angle kappa, stereoacuity, iris transillumination, macular melanin presence, foveal avascular zone, and annular reflex were recorded in 14 patients with Albinism. Spectral-domain optical coherence tomography provided macular images. RESULTS The clinical phenotype was broad, with BCVA varying from 20/20 to 20/100. Better BCVA was associated with a preserved foveal avascular zone, annular macular reflex, stereoacuity, and macular melanin. Imaging demonstrated a continuum of foveal development correlating with BCVA. Individuals with a rudimentary pit had normal inner and outer segment lengthening and better BCVA. CONCLUSIONS The spectrum of ocular structure and visual function in Albinism is broad, suggesting a possible diagnosis of Albinism in a patient with an even more normal clinical presentation.
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relationship between foveal cone specialization and pit morphology in Albinism
Investigative Ophthalmology & Visual Science, 2014Co-Authors: Melissa A. Wilk, Jennifer L. Anderson, John T Mcallister, Adam M Dubis, Kimberly E Stepien, Robert F Cooper, Teresa N Patitucci, Phyllis Summerfelt, Deborah M CostakosAbstract:Purpose. Albinism is associated with disrupted foveal development, though intersubject variability is becoming appreciated. We sought to quantify this variability, and examine the relationship between foveal cone specialization and pit morphology in patients with a clinical diagnosis of Albinism.