Camiel J. F. Boon, B. Jeroen Klevering, Carel B. Hoyng, Marijke N

Slides:

Advertisements

Similar presentations

Exome Sequencing and cis-Regulatory Mapping Identify Mutations in MAK, a Gene Encoding a Regulator of Ciliary Length, as a Cause of Retinitis Pigmentosa.

Advertisements

Basal Laminar Drusen Caused by Compound Heterozygous Variants in the CFH Gene Camiel J.F. Boon, B. Jeroen Klevering, Carel B. Hoyng, Marijke N. Zonneveld-Vrieling,

Date of download: 5/30/2016 Copyright © 2016 American Medical Association. All rights reserved. From: An Unusual Retinal Phenotype Associated With a Novel.

Supplemental Fig. 1 Pedigrees for the seven unsolved arRP families. Arrows indicate the probands underwent molecular diagnosis

Volume 123, Issue 6, Pages (June 2016)

Mutations in CTC1, Encoding the CTS Telomere Maintenance Complex Component 1, Cause Cerebroretinal Microangiopathy with Calcifications and Cysts Anne.

Volume 123, Issue 3, Pages (March 2016)

Exome Sequencing Extends the Phenotypic Spectrum for ABHD12 Mutations

Volume 122, Issue 9, Pages (September 2015)

Ocular Features of West Nile Virus Infection in North America

Full-Thickness Macular Hole after LASIK for the Correction of Myopia

Volume 1, Issue 1, Pages (January 2017)

Modern retinal laser therapy

HEREDITARY RETINAL DYSTROPHIES

Mutations in IMPG1 Cause Vitelliform Macular Dystrophies

James A. Poulter, Musallam Al-Araimi, Ivan Conte, Maria M

Pedigrees of the families of patients 1 and 2 show that the clinical phenotype co-segregates with compound heterozygous CLDN10 variants. Pedigrees of the.

Missense Mutation in the Alternative Splice Region of the PAX6 Gene in Eye Anomalies Noriyuki Azuma, Yuki Yamaguchi, Hiroshi Handa, Mutsuko Hayakawa,

Total-Genome Analysis of BRCA1/2-Related Invasive Carcinomas of the Breast Identifies Tumor Stroma as Potential Landscaper for Neoplastic Initiation

A Missense Mutation in PRPF6 Causes Impairment of pre-mRNA Splicing and Autosomal-Dominant Retinitis Pigmentosa Goranka Tanackovic, Adriana Ransijn,

The 2588G→C Mutation in the ABCR Gene Is a Mild Frequent Founder Mutation in the Western European Population and Allows the Classification of ABCR Mutations.

Newfoundland Rod-Cone Dystrophy, an Early-Onset Retinal Dystrophy, Is Caused by Splice-Junction Mutations in RLBP1 Erica R. Eichers, Jane S. Green, David.

A Nonsense Mutation in PDE6H Causes Autosomal-Recessive Incomplete Achromatopsia Susanne Kohl, Frauke Coppieters, Françoise Meire, Simone Schaich, Susanne.

Female Infertility Caused by Mutations in the Oocyte-Specific Translational Repressor PATL2 Sateesh Maddirevula, Serdar Coskun, Saad Alhassan, Atif Elnour,

Aoi Nakano, Hajime Nakano, Sal LaForgia, Leena Pulkkinen, Jouni Uitto

Volume 54, Issue 3, Pages (September 1998)

Anna M. G. Pasmooij, Hendri H. Pas, Franciska C. L

A Homozygous Mutation in the Tight-Junction Protein JAM3 Causes Hemorrhagic Destruction of the Brain, Subependymal Calcification, and Congenital Cataracts

Javier A. Couto, August Y. Huang, Dennis J. Konczyk, Jeremy A

Evangelia S. Panagiotou, Carla Sanjurjo Soriano, James A

Molecular Characterization of WFS1 in Patients with Wolfram Syndrome

Autosomal-Recessive Early-Onset Retinitis Pigmentosa Caused by a Mutation in PDE6G, the Gene Encoding the Gamma Subunit of Rod cGMP Phosphodiesterase

Peter Ianakiev, Michael W

Anna M. G. Pasmooij, Hendri H. Pas, Franciska C. L

Alice E. Davidson, Ian D. Millar, Jill E

Genotype/Phenotype Analysis of a Photoreceptor-Specific ATP-Binding Cassette Transporter Gene, ABCR, in Stargardt Disease Richard Alan Lewis, Noah F.

A Recurrent Missense Mutation in ZP3 Causes Empty Follicle Syndrome and Female Infertility Tailai Chen, Yuehong Bian, Xiaoman Liu, Shigang Zhao, Keliang.

A Mutation in the Fibroblast Growth Factor 14 Gene Is Associated with Autosomal Dominant Cerebral Ataxia John C. van Swieten, Esther Brusse, Bianca M.

Mutations in C8orf37, Encoding a Ciliary Protein, are Associated with Autosomal- Recessive Retinal Dystrophies with Early Macular Involvement Alejandro.

James A. Poulter, Manir Ali, David F

Mental Retardation and Abnormal Skeletal Development (Dyggve-Melchior-Clausen Dysplasia) Due to Mutations in a Novel, Evolutionarily Conserved Gene Daniel.

Volume 19, Issue 6, Pages (December 1997)

A Missense Mutation in the Zinc-Finger Domain of the Human Hairless Gene Underlies Congenital Atrichia in a Family of Irish Travellers Wasim Ahmad, Alan.

A Novel Point Mutation Affecting the Tyrosine Kinase Domain of the TRKA Gene in a Family with Congenital Insensitivity to Pain with Anhidrosis Shinichi.

Mutations of the Ephrin-B1 Gene Cause Craniofrontonasal Syndrome

Susanne Roosing, Ideke J. C. Lamers, Erik de Vrieze, L

Mutations in SPATA7 Cause Leber Congenital Amaurosis and Juvenile Retinitis Pigmentosa Hui Wang, Anneke I. den Hollander, Yalda Moayedi, Abuduaini Abulimiti,

Dominique J. Verlaan, Adrian M. Siegel, Guy A. Rouleau

Opitz G/BBB Syndrome in Xp22: Mutations in the MID1 Gene Cluster in the Carboxy- Terminal Domain Karin Gaudenz, Erich Roessler, Nandita Quaderi, Brunella.

Disruption of ERBB2IP Is not Associated with Dystrophic Epidermolysis Bullosa in Both Father and Son Carrying a Balanced 5;13 Translocation Margarita.

Autosomal-Dominant Striatal Degeneration Is Caused by a Mutation in the Phosphodiesterase 8B Gene Silke Appenzeller, Anja Schirmacher, Hartmut Halfter,

Mental Retardation and Abnormal Skeletal Development (Dyggve-Melchior-Clausen Dysplasia) Due to Mutations in a Novel, Evolutionarily Conserved Gene Daniel.

Figure 1 Pedigree and genetic findings

Homozygosity Mapping Reveals PDE6C Mutations in Patients with Early-Onset Cone Photoreceptor Disorders Alberta A.H.J. Thiadens, Anneke I. den Hollander,

Constitutional Mutations of the hSNF5/INI1 Gene Predispose to a Variety of Cancers Nicolas Sévenet, Eammon Sheridan, Daniel Amram, Pascale Schneider,

Mutations in POLR3A and POLR3B Encoding RNA Polymerase III Subunits Cause an Autosomal-Recessive Hypomyelinating Leukoencephalopathy Hirotomo Saitsu,

Arun Kumar, Satish C. Girimaji, Mahesh R. Duvvari, Susan H. Blanton

Mutations in CHEK2 Associated with Prostate Cancer Risk

Mutations in IMPG2, Encoding Interphotoreceptor Matrix Proteoglycan 2, Cause Autosomal-Recessive Retinitis Pigmentosa Dikla Bandah-Rozenfeld, Rob W.J.

A novel homozygous FBXO43 mutation associated with male infertility and teratozoospermia in a consanguineous Chinese family Ying Ma, Ph.D., Ning Xie,

Germline Mutations in CDH23, Encoding Cadherin-Related 23, Are Associated with Both Familial and Sporadic Pituitary Adenomas Qilin Zhang, Cheng Peng,

Mutations in UNC80, Encoding Part of the UNC79-UNC80-NALCN Channel Complex, Cause Autosomal-Recessive Severe Infantile Encephalopathy Hanan E. Shamseldin,

A Novel Claudin 16 Mutation Associated with Childhood Hypercalciuria Abolishes Binding to ZO-1 and Results in Lysosomal Mistargeting Dominik Müller,

Identification and Functional Consequences of a New Mutation (E155G) in the Gene for GCAP1 That Causes Autosomal Dominant Cone Dystrophy Susan E. Wilkie,

Anneke I. den Hollander, Robert K

Next-Generation Sequencing of a 40 Mb Linkage Interval Reveals TSPAN12 Mutations in Patients with Familial Exudative Vitreoretinopathy Konstantinos Nikopoulos,

Exon Skipping in IVD RNA Processing in Isovaleric Acidemia Caused by Point Mutations in the Coding Region of the IVD Gene Jerry Vockley, Peter K. Rogan,

Arts Syndrome Is Caused by Loss-of-Function Mutations in PRPS1

Glycyl tRNA Synthetase Mutations in Charcot-Marie-Tooth Disease Type 2D and Distal Spinal Muscular Atrophy Type V Anthony Antonellis, Rachel E. Ellsworth,

Homozygous WNT3 Mutation Causes Tetra-Amelia in a Large Consanguineous Family Stephan Niemann, Chengfeng Zhao, Filon Pascu, Ulrich Stahl, Ute Aulepp,

Presentation transcript:

Basal Laminar Drusen Caused by Compound Heterozygous Variants in the CFH Gene Camiel J.F. Boon, B. Jeroen Klevering, Carel B. Hoyng, Marijke N. Zonneveld-Vrieling, Sander B. Nabuurs, Ellen Blokland, Frans P.M. Cremers, Anneke I. den Hollander The American Journal of Human Genetics Volume 82, Issue 2, Pages 516-523 (February 2008) DOI: 10.1016/j.ajhg.2007.11.007 Copyright © 2008 The American Society of Human Genetics Terms and Conditions

Figure 1 Fluorescein Angiogram of the Basal-Laminar Drusen Phenotype Typical fluorescein angiogram of a patient with advanced drusen maculopathy resembling basal laminar drusen (patient 9). Note the typical “stars-in-the-sky” appearance, with central confluence of drusen and the small pseudovitelliform pigment epithelial detachment. The American Journal of Human Genetics 2008 82, 516-523DOI: (10.1016/j.ajhg.2007.11.007) Copyright © 2008 The American Society of Human Genetics Terms and Conditions

Figure 2 Molecular Genetic Analysis of the CFH Gene in Families Affected with Drusen Maculopathy (A and B) Seven affected individuals in two families are compound heterozygous for the nonsense mutation Gln408X and the AMD risk allele Tyr402His. Brackets flanking the CFH variants of A-I.3 indicate that they were deduced through CA-marker analysis. (C) Three affected individuals in a third family are compound heterozygous for the missense variant Arg1078Ser and Tyr402His. (D) Patient D is homozygous for the Tyr402His variant, and in addition, he carries a heterozygous variant in the splice-donor site of exon 3 (c.350+6T→G). (E) A patient in a fifth family carries a heterozygous amino acid variant (Arg567Gly) and is heterozygous for the Tyr402His variant. Segregation analysis could not be performed. Grey pedigree symbols denote patients with basal laminar drusen. The black symbols denote two females affected with AMD. Numbers in the pedigree symbols reflect current age. (F) Sequences of heterozygous variants detected in the CFH gene. The American Journal of Human Genetics 2008 82, 516-523DOI: (10.1016/j.ajhg.2007.11.007) Copyright © 2008 The American Society of Human Genetics Terms and Conditions

Figure 3 Retinal Phenotypes of Drusen Patients Carrying the Combination of a Gln408X Mutation and the Tyr402His AMD Risk Variant (A–D) Retinal phenotype of patient A-III.5. (A) Fundus photograph of the right eye, showing extensive chorioretinal atrophy of the posterior pole. At the first examination, 17 years earlier, these areas corresponded with large confluent drusen with incipient atrophy. (B) The short-wavelength fundus autofluorescence (FAF) image shows an absence of FAF corresponding with the patches of chorioretinal atrophy, not only in the macular area but also in the midperipheral retina. Moreover, diffuse changes in FAF intensity can be observed. (C) Fundus photograph of the left eye, showing large confluent drusen and mild chorioretinal atrophy. (D) An infrared reflectance photograph clearly visualizes small, round, midperipheral drusen scattered between the patches of chorioretinal atrophy. The drusen seen with infrared reflectance corresponded with the discrete, round, yellow-white drusen with a slightly pigmented border seen on ophthalmoscopy. (E–H) Retinal phenotype of patient B-II.1. (E) Fundus photograph showing confluent macular drusen. (F) The macular drusen can be more easily detected on the fluorescein angiogram. (G) Optical coherence tomography (OCT, oblique section) showing small dome-shaped elevations of the “outer red line,” which correspond with the visible drusen on ophthalmoscopy (arrow). (H) Similar to patient A-III.5, small midperipheral drusen were seen in this patient, and OCT revealed aspects similar to the macular drusen. (I and J) Fluorescein angiography showed tiny hyperfluorescent drusen in the parafoveal area and in the (mid-) peripheral retina of Patient B-III.2 (the 22-year-old asymptomatic son of patient B-II.1), but the drusen were difficult to discern on ophthalmoscopy. His 25-year-old brother (B-III.1) had similar midperipheral lesions, but to a lesser extent. The American Journal of Human Genetics 2008 82, 516-523DOI: (10.1016/j.ajhg.2007.11.007) Copyright © 2008 The American Society of Human Genetics Terms and Conditions

Figure 4 Molecular Modeling of Missense Variants Detected in CFH (A and B) Model of the SCR18 domain, depicting the effect of the Arg1078Ser variant. (A) wild-type sequence (Arg1078). (B) Arg1078Ser variant. (C and D) Model of the SCR9 and SCR10 domains, depicting the effect of the Arg567Gly variant. (C) wild-type sequence (Arg567). (D) Arg567Gly variant. The SCR9 domain is shown in yellow, the SCR10 domain in orange, and the linker region between the two domains is shown in blue. Hydrogen-bonding partners for the residues in the linker region are indicated with dotted lines. All figures were made with Yasara. The American Journal of Human Genetics 2008 82, 516-523DOI: (10.1016/j.ajhg.2007.11.007) Copyright © 2008 The American Society of Human Genetics Terms and Conditions