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

Slides:

Advertisements

Similar presentations

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

Advertisements

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

Recessive HYDIN Mutations Cause Primary Ciliary Dyskinesia without Randomization of Left-Right Body Asymmetry Heike Olbrich, Miriam Schmidts, Claudius.

Use of Homozygosity Mapping to Identify a Region on Chromosome 1 Bearing a Defective Gene That Causes Autosomal Recessive Homozygous Hypercholesterolemia.

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

Mutations in TPRN Cause a Progressive Form of Autosomal-Recessive Nonsyndromic Hearing Loss Yun Li, Esther Pohl, Redouane Boulouiz, Margit Schraders,

Cohen Syndrome Is Caused by Mutations in a Novel Gene, COH1, Encoding a Transmembrane Protein with a Presumed Role in Vesicle-Mediated Sorting and Intracellular.

Syndromic Short Stature in Patients with a Germline Mutation in the LIM Homeobox LHX4 Kalotina Machinis, Jacques Pantel, Irène Netchine, Juliane Léger,

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

A Defect in the TUSC3 Gene Is Associated with Autosomal Recessive Mental Retardation Masoud Garshasbi, Valeh Hadavi, Haleh Habibi, Kimia Kahrizi, Roxana.

Volume 54, Issue 3, Pages (September 1998)

Gail Billingsley, Sathiyavedu T. Santhiya, Andrew D

Volume 54, Issue 3, Pages (September 1998)

Germline BHD-Mutation Spectrum and Phenotype Analysis of a Large Cohort of Families with Birt-Hogg-Dubé Syndrome Laura S. Schmidt, Michael L. Nickerson,

Progress in Molecular Genetics of Heritable Skin Diseases: The Paradigms of Epidermolysis Bullosa and Pseudoxanthoma Elasticum Jouni Uitto, Leena Pulkkinen,

Mutations in a Novel Gene with Transmembrane Domains Underlie Usher Syndrome Type 3 Tarja Joensuu, Riikka Hämäläinen, Bo Yuan, Cheryl Johnson, Saara.

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

The c.1364C>A (p.A455E) Mutation in the CFTR Pseudogene Results in an Incorrectly Assigned Carrier Status by a Commonly Used Screening Platform Kristin.

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

Size Polymorphisms in the Human Ultrahigh Sulfur Hair Keratin-Associated Protein 4, KAP4, Gene Family Naoyuki Kariya, Yutaka Shimomura, Masaaki Ito

Rare Missense and Synonymous Variants in UBE1 Are Associated with X-Linked Infantile Spinal Muscular Atrophy Juliane Ramser, Mary Ellen Ahearn, Claus.

Haplotype-Sharing Analysis Implicates Chromosome 7q36 Harboring DPP6 in Familial Idiopathic Ventricular Fibrillation Marielle Alders, Tamara T. Koopmann,

Mutations in TRIOBP, Which Encodes a Putative Cytoskeletal-Organizing Protein, Are Associated with Nonsyndromic Recessive Deafness Saima Riazuddin, Shaheen.

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.

DVL1 Frameshift Mutations Clustering in the Penultimate Exon Cause Autosomal- Dominant Robinow Syndrome Janson White, Juliana F. Mazzeu, Alexander Hoischen,

Duplication of the MECP2 Region Is a Frequent Cause of Severe Mental Retardation and Progressive Neurological Symptoms in Males Hilde Van Esch, Marijke.

Thomas C. Hart, Yingze Zhang, Michael C. Gorry, P

Mutations in CABP4, the Gene Encoding the Ca2+-Binding Protein 4, Cause Autosomal Recessive Night Blindness Christina Zeitz, Barbara Kloeckener-Gruissem,

John D. Rioux, Valerie A. Stone, Mark J

A Homozygous Nonsense Mutation in Type XVII Collagen Gene (COL17A1) Uncovers an Alternatively Spliced mRNA Accounting for an Unusually Mild Form of Non-Herlitz.

A Nonsense Mutation in CRYBB1 Associated with Autosomal Dominant Cataract Linked to Human Chromosome 22q Donna S. Mackay, Olivera B. Boskovska, Harry.

A Presenilin-1 Truncating Mutation Is Present in Two Cases with Autopsy-Confirmed Early-Onset Alzheimer Disease Carolyn Tysoe, Joanne Whittaker, John.

Mutations of MYO6 Are Associated with Recessive Deafness, DFNB37

A Mutation Hot Spot for Nonspecific X-Linked Mental Retardation in the MECP2 Gene Causes the PPM-X Syndrome Sabine M. Klauck, Susan Lindsay, Kim S. Beyer,

Airong Li, Sonia Davila, Laszlo Furu, Qi Qian, Xin Tian, Patrick S

A Heterozygous Truncating Mutation in RRM2B Causes Autosomal-Dominant Progressive External Ophthalmoplegia with Multiple mtDNA Deletions Henna Tyynismaa,

Gail Billingsley, Sathiyavedu T. Santhiya, Andrew D

CC2D2A, Encoding A Coiled-Coil and C2 Domain Protein, Causes Autosomal- Recessive Mental Retardation with Retinitis Pigmentosa Abdul Noor, Christian Windpassinger,

Sadaf Naz, Chantal M. Giguere, David C. Kohrman, Kristina L

A Mutation in the Variable Repeat Region of the Aggrecan Gene (AGC1) Causes a Form of Spondyloepiphyseal Dysplasia Associated with Severe, Premature.

Exome Sequencing Identifies a DYNC1H1 Mutation in a Large Pedigree with Dominant Axonal Charcot-Marie-Tooth Disease Michael N. Weedon, Robert Hastings,

Lack of EVER2 Protein in Two Epidermodysplasia Verruciformis Patients with Skin Cancer Presenting Previously Unreported Homozygous Genetic Deletions in.

John A. Martignetti, Karen E

Mutations in SPINT2 Cause a Syndromic Form of Congenital Sodium Diarrhea Peter Heinz-Erian, Thomas Müller, Birgit Krabichler, Melanie Schranz, Christian.

DVL3 Alleles Resulting in a −1 Frameshift of the Last Exon Mediate Autosomal- Dominant Robinow Syndrome Janson J. White, Juliana F. Mazzeu, Alexander.

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

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

Identification of FOXP2 Truncation as a Novel Cause of Developmental Speech and Language Deficits Kay D. MacDermot, Elena Bonora, Nuala Sykes, Anne-Marie.

A Defect in the TUSC3 Gene Is Associated with Autosomal Recessive Mental Retardation Masoud Garshasbi, Valeh Hadavi, Haleh Habibi, Kimia Kahrizi, Roxana.

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

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,

Volume 57, Issue 3, Pages (March 2000)

Hereditary Isolated Renal Magnesium Loss Maps to Chromosome 11q23

Oligodontia Is Caused by Mutation in LTBP3, the Gene Encoding Latent TGF-β Binding Protein 3 Abdul Noor, Christian Windpassinger, Irina Vitcu, Marija.

Volume 53, Issue 5, Pages (May 1998)

Exome Sequencing Identifies CCDC8 Mutations in 3-M Syndrome, Suggesting that CCDC8 Contributes in a Pathway with CUL7 and OBSL1 to Control Human Growth

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

Volume 93, Issue 1, Pages (April 1998)

The Tumor-Necrosis-Factor Receptor–Associated Periodic Syndrome: New Mutations in TNFRSF1A, Ancestral Origins, Genotype-Phenotype Studies, and Evidence.

Mutations in PTPRQ Are a Cause of Autosomal-Recessive Nonsyndromic Hearing Impairment DFNB84 and Associated with Vestibular Dysfunction Margit Schraders,

Akio Tanaka, Sarah Weinel, Nikoletta Nagy, Mark O'Driscoll, Joey E

Cohen Syndrome Is Caused by Mutations in a Novel Gene, COH1, Encoding a Transmembrane Protein with a Presumed Role in Vesicle-Mediated Sorting and Intracellular.

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,

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

Duplication of the MECP2 Region Is a Frequent Cause of Severe Mental Retardation and Progressive Neurological Symptoms in Males Hilde Van Esch, Marijke.

A, Schematic diagram of identified splice variants of PD-L1.

BMPER Mutation in Diaphanospondylodysostosis Identified by Ancestral Autozygosity Mapping and Targeted High-Throughput Sequencing Vincent A. Funari,

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

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:

Mutation of Solute Carrier SLC16A12 Associates with a Syndrome Combining Juvenile Cataract with Microcornea and Renal Glucosuria Barbara Kloeckener-Gruissem, Kristof Vandekerckhove, Gudrun Nürnberg, John Neidhardt, Christina Zeitz, Peter Nürnberg, Isaak Schipper, Wolfgang Berger The American Journal of Human Genetics Volume 82, Issue 3, Pages 772-779 (March 2008) DOI: 10.1016/j.ajhg.2007.12.013 Copyright © 2008 The American Society of Human Genetics Terms and Conditions

Figure 1 Pedigree of Swiss Family Segregating Juvenile Cataract with Microcornea and Glucosuria Modified after Vandekerckhove et al.7 Filled symbols represent affected status for all three phenotypes, with three exceptions indicated by star; III-1 and III-2 are negative and III-5 is borderline for glucosuria (Table 1). Five-digit laboratory identification numbers (given below pedigree symbols) were assigned prior to DNA extraction. Family members IV-2 and IV-3 were not tested for any of the three phenotypes. The American Journal of Human Genetics 2008 82, 772-779DOI: (10.1016/j.ajhg.2007.12.013) Copyright © 2008 The American Society of Human Genetics Terms and Conditions

Figure 2 Cataract and Microcornea Phenotype of Patient III-5 Preoperative cortico-nuclear cataract in right eye is shown in (A) and microcornea (9.8 × 9.5 mm) in (B). The American Journal of Human Genetics 2008 82, 772-779DOI: (10.1016/j.ajhg.2007.12.013) Copyright © 2008 The American Society of Human Genetics Terms and Conditions

Figure 3 LOD Scores across the Genome for the Phenotype of Cataract with Microcornea Chromosome number and genetic distances in cM (centi Morgan) is horizontally displayed; LOD score is given along the vertical axis. The American Journal of Human Genetics 2008 82, 772-779DOI: (10.1016/j.ajhg.2007.12.013) Copyright © 2008 The American Society of Human Genetics Terms and Conditions

Figure 4 Haplotypes for the Cataract-Linked Region on Chromosome 10 Recombinations in patients 26808 (III-4) and 26274 (IV-1) define a critical interval of 2.6 Mega bases (Mb) delimited by markers SNP_A_1510595 (rs701826) (∗) and SNP_A_1511227 (rs2254391) (∗∗) at positions 108.48 and 111.55 cM, respectively. Disease chromosome in red. The American Journal of Human Genetics 2008 82, 772-779DOI: (10.1016/j.ajhg.2007.12.013) Copyright © 2008 The American Society of Human Genetics Terms and Conditions

Figure 5 Mutation Screening in SCL16A12 Electropherogram shows the mutation in exon 6 within the context of 21 nucleotides. Shown are both the DNA sequence of the unaffected individual III-9 (A) and the heterozygous change of C→T (Y) in the affected individual III- 8 (B). The genotypes are given in brackets. Translation codons are underlined and amino acid identity is written below with single letter code. The American Journal of Human Genetics 2008 82, 772-779DOI: (10.1016/j.ajhg.2007.12.013) Copyright © 2008 The American Society of Human Genetics Terms and Conditions

Figure 6 Expression Studies of SLC16A12 (A) Schematic representation of exons. Protein coding regions are displayed in darker shade. Translation initiates within exon 3 (vertical arrow, ATG) and terminates within exon 8 (vertical arrow, STOP). Mutation, c.643C→T, in exon 6 (vertical arrow) is predicted to lead to a premature termination. Positions of primers are indicated by forward and reverse horizontal arrows, yielding RT-PCR product a (exon spanning 4_5 to exon 6) and product b (exon 3 to exon 5). (B) RT-PCR analyses from human tissues with commercially available mRNA. Primers to yield product a were used to amplify SLC16A12 transcripts. RNA Polymerase II (POLR2A) transcripts served as endogenous control. (C) RT-PCR analysis from tissues isolated from a single human donor eye. Primers to yield product b of SLC16A12 and of POLR2A (control) were used for amplification. Lens RNA was 3-fold concentrated compared to the other samples. The American Journal of Human Genetics 2008 82, 772-779DOI: (10.1016/j.ajhg.2007.12.013) Copyright © 2008 The American Society of Human Genetics Terms and Conditions

Figure 7 Schematic Representation of the Predicted Secondary Structure of SLC16A12 Prediction of membrane topology revealed a 536 amino acid protein with 12 transmembrane domains separated by intra- and extracellular domains of varying lengths with both termini (NH2 and COOH) located intracellularly. Amino acid glutamin (Gln, Q) at position 215 is mutated to a stop in the patients described herein (red circle). The American Journal of Human Genetics 2008 82, 772-779DOI: (10.1016/j.ajhg.2007.12.013) Copyright © 2008 The American Society of Human Genetics Terms and Conditions