Complement Factor H Gene Mutation Associated with Autosomal Recessive Atypical Hemolytic Uremic Syndrome Lihua Ying, Yitzhak Katz, Menachem Schlesinger,

Slides:

Advertisements

Similar presentations

Deletions of the INK4A Gene Occur in Malignant Peripheral Nerve Sheath Tumors but not in Neurofibromas Helen P. Kourea, Irene Orlow, Bernd W. Scheithauer,

Advertisements

Linkage and Association Studies Identify a Novel Locus for Alzheimer Disease at 7q36 in a Dutch Population-Based Sample Rosa Rademakers, Marc Cruts,

Identification of a Major Susceptibility Locus for Restless Legs Syndrome on Chromosome 12q Alex Desautels, Gustavo Turecki, Jacques Montplaisir, Adolfo.

Homozygous Defects in LMNA, Encoding Lamin A/C Nuclear-Envelope Proteins, Cause Autosomal Recessive Axonal Neuropathy in Human (Charcot-Marie-Tooth Disorder.

Localization of a Gene for Molybdenum Cofactor Deficiency, on the Short Arm of Chromosome 6, by Homozygosity Mapping Adel Shalata, Hanna Mandel, Jochen.

Stephan Züchner, Gaofeng Wang, Khanh-Nhat Tran-Viet, Martha A

P. M. Kelley, D. J. Harris, B. C. Comer, J. W. Askew, T. Fowler, S. D

Tracy Dixon-Salazar, Jennifer L. Silhavy, Sarah E. Marsh, Carrie M

Familial Deafness, Congenital Heart Defects, and Posterior Embryotoxon Caused by Cysteine Substitution in the First Epidermal-Growth-Factor–Like Domain.

Genomewide Linkage Scan Identifies a Novel Susceptibility Locus for Restless Legs Syndrome on Chromosome 9p Shenghan Chen, William G. Ondo, Shaoqi Rao,

A Genetic Factor for Age-Related Cataract: Identification and Characterization of a Novel Galactokinase Variant, “Osaka,” in Asians Yoshiyuki Okano,

A Novel Alu-Like Element Rearranged in the Dystrophin Gene Causes a Splicing Mutation in a Family with X-Linked Dilated Cardiomyopathy Alessandra Ferlini,

Volume 69, Issue 6, Pages (March 2006)

Tamara Rogers, David Chandler, Dora Angelicheva, P. K

A Family with Isolated Hyperparathyroidism Segregating a Missense MEN1 Mutation and Showing Loss of the Wild-Type Alleles in the Parathyroid Tumors Bin.

Mutations of SURF-1 in Leigh Disease Associated with Cytochrome c Oxidase Deficiency Valeria Tiranti, Konstanze Hoertnagel, Rosalba Carrozzo, Claudia.

A Gene Mutated in Nephronophthisis and Retinitis Pigmentosa Encodes a Novel Protein, Nephroretinin, Conserved in Evolution Edgar Otto, Julia Hoefele,

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

Novel Homozygous and Compound Heterozygous COL17A1 Mutations Associated with Junctional Epidermolysis Bullosa Michaela Floeth, Heike Schäcke, Nadja Hammami-Hauasli,

Structure of the GM2A Gene: Identification of an Exon 2 Nonsense Mutation and a Naturally Occurring Transcript with an In-Frame Deletion of Exon 2 Biao.

Survival of Male Patients with Incontinentia Pigmenti Carrying a Lethal Mutation Can Be Explained by Somatic Mosaicism or Klinefelter Syndrome The.

Isolated 2-Methylbutyrylglycinuria Caused by Short/Branched-Chain Acyl-CoA Dehydrogenase Deficiency: Identification of a New Enzyme Defect, Resolution.

Pseudoexon Activation as a Novel Mechanism for Disease Resulting in Atypical Growth- Hormone Insensitivity Louise A. Metherell, Scott A. Akker, Patricia.

Per M. Knappskog, Jacek Majewski, Avi Livneh, Per Torgeir E

A Gene for Familial Juvenile Polyposis Maps to Chromosome 18q21.1

Kimberly C. Sippel, Rebecca E. Fraioli, Gary D. Smith, Mary E

Michaela Floeth, Leena Bruckner-Tuderman

Mutation of Solute Carrier SLC16A12 Associates with a Syndrome Combining Juvenile Cataract with Microcornea and Renal Glucosuria Barbara Kloeckener-Gruissem,

ATM Mutations and Phenotypes in Ataxia-Telangiectasia Families in the British Isles: Expression of Mutant ATM and the Risk of Leukemia, Lymphoma, and.

Mitochondrial Complex III Deficiency Associated with a Homozygous Mutation in UQCRQ Ortal Barel, Zamir Shorer, Hagit Flusser, Rivka Ofir, Ginat Narkis,

Genetic studies into inherited and sporadic hemolytic uremic syndrome

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.

Amplification Refractory Mutation System, a Highly Sensitive and Simple Polymerase Chain Reaction Assay, for the Detection of JAK2 V617F Mutation in Chronic.

Koji Suzuki, Tania Bustos, Richard A. Spritz

Genetic Linkage of Autosomal-Dominant Alport Syndrome with Leukocyte Inclusions and Macrothrombocytopenia (Fechtner Syndrome) to Chromosome 22q11-13

Lethal Contractural Syndrome Type 3 (LCCS3) Is Caused by a Mutation in PIP5K1C, Which Encodes PIPKIγ of the Phophatidylinsitol Pathway Ginat Narkis,

Homozygosity and Linkage-Disequilibrium Mapping of the Syndrome of Congenital Hypoparathyroidism, Growth and Mental Retardation, and Dysmorphism to a.

John A. Martignetti, Karen E

Evidence That the Penetrance of Mutations at the RP11 Locus Causing Dominant Retinitis Pigmentosa Is Influenced by a Gene Linked to the Homologous RP11.

PEX3 Is the Causal Gene Responsible for Peroxisome Membrane Assembly–Defective Zellweger Syndrome of Complementation Group G Kamran Ghaedi, Masanori.

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

Recurrence of Marfan Syndrome as a Result of Parental Germ-Line Mosaicism for an FBN1 Mutation Terhi Rantamäki, Ilkka Kaitila, Ann-Christine Syvänen,

Hyperchlorhidrosis Caused by Homozygous Mutation in CA12, Encoding Carbonic Anhydrase XII Maya Feldshtein, Suliman Elkrinawi, Baruch Yerushalmi, Barak.

Volume 78, Issue 8, Pages (October 2010)

Gabriella Esposito, Giuseppe Rescigno, Francesco Salvatore

Recurrence of the T666M Calcium Channel CACNA1A Gene Mutation in Familial Hemiplegic Migraine with Progressive Cerebellar Ataxia A. Ducros, C. Denier,

Compound Heterozygosity for Novel Splice Site Mutations in the BPAG2/COL17A1 Gene Underlies Generalized Atrophic Benign Epidermolysis Bullosa Leena Pulkkinen,

Tightly Clustered 11q23 and 22q11 Breakpoints Permit PCR-Based Detection of the Recurrent Constitutional t(11;22) Hiroki Kurahashi, Tamim H. Shaikh,

A Unique Point Mutation in the PMP22 Gene Is Associated with Charcot-Marie-Tooth Disease and Deafness Margaret J. Kovach, Jing-Ping Lin, Simeon Boyadjiev,

Tracy Dixon-Salazar, Jennifer L. Silhavy, Sarah E. Marsh, Carrie M

Volume 57, Issue 6, Pages (June 2000)

Adaptor Protein Complex 4 Deficiency Causes Severe Autosomal-Recessive Intellectual Disability, Progressive Spastic Paraplegia, Shy Character, and Short.

Volume 71, Issue 6, Pages (March 2007)

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

Bart A. Jessen, Marjorie A. Phillips, Robert H. Rice

A Gene for an Autosomal Dominant Scleroatrophic Syndrome Predisposing to Skin Cancer (Huriez Syndrome) Maps to Chromosome 4q23 Young-Ae Lee, Howard P.

Identification and Characterization of a Mutation, in the Human UDP-Galactose-4- Epimerase Gene, Associated with Generalized Epimerase-Deficiency Galactosemia

A Gene for Autosomal Recessive Spondylocostal Dysostosis Maps to 19q13

Alexandre Irrthum, Marika J

C. Denier, S. Goutagny, P. Labauge, V. Krivosic, M Arnoult, A

Kit-Sing Au, Adelaide A. Hebert, E. Steve Roach, Hope Northrup

Epigenetic Allele Silencing Unveils Recessive RYR1 Mutations in Core Myopathies Haiyan Zhou, Martin Brockington, Heinz Jungbluth, David Monk, Philip Stanier,

Niemann-Pick Disease Type C: Spectrum of HE1 Mutations and Genotype/Phenotype Correlations in the NPC2 Group Gilles Millat, Karim Chikh, Saule Naureckiene,

Comparative Genomic Analysis Identifies an ADP-Ribosylation Factor–like Gene as the Cause of Bardet-Biedl Syndrome (BBS3) Annie P. Chiang, Darryl Nishimura,

Darryl Y. Nishimura, Ruth E. Swiderski, Charles C. Searby, Erik M

Identification of a New Splice Form of the EDA1 Gene Permits Detection of Nearly All X- Linked Hypohidrotic Ectodermal Dysplasia Mutations Alex W. Monreal,

Fang Wang, Yunfeng Wang, Jie Ding, Jiyun Yang Kidney International

A Locus for Autosomal Dominant Hereditary Spastic Ataxia, SAX1,Maps to Chromosome 12p13 I.A. Meijer, C.K. Hand, K.K. Grewal, M.G. Stefanelli, E.J. Ives,

K. Miura, M. Obama, K. Yun, H. Masuzaki, Y. Ikeda, S. Yoshimura, T

Linkage and Association Studies Identify a Novel Locus for Alzheimer Disease at 7q36 in a Dutch Population-Based Sample Rosa Rademakers, Marc Cruts,

Presentation transcript:

Complement Factor H Gene Mutation Associated with Autosomal Recessive Atypical Hemolytic Uremic Syndrome Lihua Ying, Yitzhak Katz, Menachem Schlesinger, Rivka Carmi, Hanna Shalev, Neena Haider, Gretel Beck, Val C. Sheffield, Daniel Landau The American Journal of Human Genetics Volume 65, Issue 6, Pages 1538-1546 (December 1999) DOI: 10.1086/302673 Copyright © 1999 The American Society of Human Genetics Terms and Conditions

Figure 1 Family pedigree and genotypes. Blackened symbols denote affected individuals; unblackened symbols, unaffected individuals; unblackened diamond, CVS. I–VII denote generation. The ID numbers for each member of generations V–VII are listed below each symbol. Genotypes of both flanking and linked markers are shown below ID numbers. Note that all the affected individuals are homozygous for the markers between flanking markers D1S408 and D1S1647. Only the markers defining the critical region are listed. The American Journal of Human Genetics 1999 65, 1538-1546DOI: (10.1086/302673) Copyright © 1999 The American Society of Human Genetics Terms and Conditions

Figure 2 Representative genotypes with marker D1S1160. Twenty-three DNA samples from the HUS kindred were analyzed by PCR with D1S1660. The ID numbers for each lane are shown. The unaffected parents are individuals V-1 and V-2, V-10 and V-11, and V-4 and V-5. Lanes labeled with an “S” represent the siblings who do not show in the pedigree but were included in the genotyping. Two affected individuals genotyped are VI-4 and VI-24. All affected individuals are homozygous for marker D1S1160. Similar results were obtained with other linked STRPs (data not shown). The American Journal of Human Genetics 1999 65, 1538-1546DOI: (10.1086/302673) Copyright © 1999 The American Society of Human Genetics Terms and Conditions

Figure 3 A, SSCP of exon 20 in family members with HUS. DNA samples were screened for mutations, by use of SSCP with primers from the CFH coding region. The ID numbers for each lane are shown. A CVS was included in lane 16 (VII-4). Note the shifted bands representing a mutation in the CFH gene. B, Partial chromatograms for the exon 20 codon sequence for affected individuals (VI-4) and for unaffected individuals (VI-15). Note the mutation in affected individuals (C→T change). The American Journal of Human Genetics 1999 65, 1538-1546DOI: (10.1086/302673) Copyright © 1999 The American Society of Human Genetics Terms and Conditions

Figure 4 Western blot analysis of serum CFH from affected individuals VII-2 (lanes 1–3), VI-4 (lanes 7–9), and VI-24 (lanes 10–12); from unaffected parents VI-19 (lane 4) and V-7 (lane 5); and from sibling VII-3 (lane 6). P1 and P2 are the pools of unaffected individuals corresponding to VII-2 and VI-4, respectively. The blot was probed with antisera specific for CFH. Size markers are shown. The serum dilutions are indicated below each lane. The American Journal of Human Genetics 1999 65, 1538-1546DOI: (10.1086/302673) Copyright © 1999 The American Society of Human Genetics Terms and Conditions

Figure 5 The correlation between serum CFH and C3. Immunodiffusion assay of serum from peripheral blood of unaffected parents and siblings. CFH and C3 were measured with the use of monospecific goat antibodies to human C complement. The protein counts were expressed as a percentage of pooled normal sera. Correlation: r=0.67, P<.05. The American Journal of Human Genetics 1999 65, 1538-1546DOI: (10.1086/302673) Copyright © 1999 The American Society of Human Genetics Terms and Conditions

Figure 6 CFH mRNA: northern blot analysis of fibroblasts from affected individuals VII-2 (lanes 1 and 2), VI-4 (lanes 3 and 4) and from unaffected control individuals C1 (lanes 5 and 6) and C2 (lanes 7 and 8), in both the basal state (B) and the stimulated state (S). The blot was probe with a CFH cDNA probe. An internal control probe (C1I [complement 1 inhibitor]) was included. Size markers are not shown. The American Journal of Human Genetics 1999 65, 1538-1546DOI: (10.1086/302673) Copyright © 1999 The American Society of Human Genetics Terms and Conditions

Figure 7 CFH and C3 biosynthesis and secretion. Pulse-chase experiments of CFH (A) and C3 (B) from skin fibroblasts from two patients (denoted by “HUS”) (VI-4 and VII-2) and from two healthy controls (denoted by “control”). Intracellular biosynthesis or extracellular secretion rate at 0 h is denoted by gray bars; at 2 h, by unblackened bars; and at 8 h, by blackened bars. IC = inside fibroblasts; EC = in medium. The American Journal of Human Genetics 1999 65, 1538-1546DOI: (10.1086/302673) Copyright © 1999 The American Society of Human Genetics Terms and Conditions