Targeted Next-Generation Sequencing of a 12

Slides:

Advertisements

Similar presentations

Mutations in DDHD2, Encoding an Intracellular Phospholipase A1, Cause a Recessive Form of Complex Hereditary Spastic Paraplegia Janneke H.M. Schuurs-Hoeijmakers,

Advertisements

Biallelic Mutations in TMTC3, Encoding a Transmembrane and TPR-Containing Protein, Lead to Cobblestone Lissencephaly Julie Jerber, Maha S. Zaki, Jumana.

A Single SNP in an Evolutionary Conserved Region within Intron 86 of the HERC2 Gene Determines Human Blue-Brown Eye Color Richard A. Sturm, David L.

Figure 2 Sanger sequencing, conservation, and summary of known ACO2 mutations Sanger sequencing, conservation, and summary of known ACO2 mutations (A)

Mutations in SLC30A10 Cause Parkinsonism and Dystonia with Hypermanganesemia, Polycythemia, and Chronic Liver Disease Marialuisa Quadri, Antonio Federico,

Homozygosity Mapping Reveals Mutations of GRXCR1 as a Cause of Autosomal- Recessive Nonsyndromic Hearing Impairment Margit Schraders, Kwanghyuk Lee, Jaap.

Novel PMS2 Pseudogenes Can Conceal Recessive Mutations Causing a Distinctive Childhood Cancer Syndrome Michel De Vos, Bruce E. Hayward, Susan Picton,

Ilse Feenstra, Lisenka E. L. M. Vissers, Ronald J. E

A Homozygous Missense Mutation in TGM5 Abolishes Epidermal Transglutaminase 5 Activity and Causes Acral Peeling Skin Syndrome Andrew J. Cassidy, Maurice.

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

Ultra-sensitive Sequencing Identifies High Prevalence of Clonal Hematopoiesis- Associated Mutations throughout Adult Life Rocio Acuna-Hidalgo, Hilal Sengul,

Exome Sequencing in Brown-Vialetto-Van Laere Syndrome

Identification of a novel mutation in PLA2G6 gene in a Chinese pedigree with familial cortical myoclonic tremor with epilepsy Lehong Gao, Liping Li,

Biallelic Mutations in TMTC3, Encoding a Transmembrane and TPR-Containing Protein, Lead to Cobblestone Lissencephaly Julie Jerber, Maha S. Zaki, Jumana.

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

TBC1D24, an ARF6-Interacting Protein, Is Mutated in Familial Infantile Myoclonic Epilepsy Antonio Falace, Fabia Filipello, Veronica La Padula, Nicola.

A Single SNP in an Evolutionary Conserved Region within Intron 86 of the HERC2 Gene Determines Human Blue-Brown Eye Color Richard A. Sturm, David L.

Design and Validation of a Conformation Sensitive Capillary Electrophoresis-Based Mutation Scanning System and Automated Data Analysis of the More than.

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

Mutations in PADI6 Cause Female Infertility Characterized by Early Embryonic Arrest Yao Xu, Yingli Shi, Jing Fu, Min Yu, Ruizhi Feng, Qing Sang, Bo Liang,

Exome Sequencing Identifies Truncating Mutations in Human SERPINF1 in Autosomal- Recessive Osteogenesis Imperfecta Jutta Becker, Oliver Semler, Christian.

The prevalence of digenic mutations in patients with normosmic hypogonadotropic hypogonadism and Kallmann syndrome Samuel D. Quaynor, M.S., Hyung-Goo.

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

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,

Utility of NIST Whole-Genome Reference Materials for the Technical Validation of a Multigene Next-Generation Sequencing Test Bennett O.V. Shum, Ilya.

A Recurrent Intragenic Deletion in the Desmoglein 4 Gene Underlies Localized Autosomal Recessive Hypotrichosis Celia Moss, Amalia Martinez-Mir, HaMut.

Peter Ianakiev, Michael W

A Truncating Mutation of TRAPPC9 Is Associated with Autosomal-Recessive Intellectual Disability and Postnatal Microcephaly Ganeshwaran H. Mochida, Muhammad.

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

Mutations in BICD2, which Encodes a Golgin and Important Motor Adaptor, Cause Congenital Autosomal-Dominant Spinal Muscular Atrophy Kornelia Neveling,

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

Christian Gilissen, Heleen H

Cantú Syndrome Is Caused by Mutations in ABCC9

Guofang Hu, Meltem Önder, Melissa Gill, Burhan Aksakal, Murat Öztas, M

Michael R. Knowles, Margaret W. Leigh, Lawrence E

Splitting p63 The American Journal of Human Genetics

ELAC2 Mutations Cause a Mitochondrial RNA Processing Defect Associated with Hypertrophic Cardiomyopathy Tobias B. Haack, Robert Kopajtich, Peter Freisinger,

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.

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

Mutations in SCARF2 Are Responsible for Van Den Ende-Gupta Syndrome

TBC1D24, an ARF6-Interacting Protein, Is Mutated in Familial Infantile Myoclonic Epilepsy Antonio Falace, Fabia Filipello, Veronica La Padula, Nicola.

Biallelic Mutations in PATL2 Cause Female Infertility Characterized by Oocyte Maturation Arrest Biaobang Chen, Zhihua Zhang, Xiaoxi Sun, Yanping Kuang,

Identification of Mutations in TRAPPC9, which Encodes the NIK- and IKK-β-Binding Protein, in Nonsyndromic Autosomal-Recessive Mental Retardation Asif.

Novel PMS2 Pseudogenes Can Conceal Recessive Mutations Causing a Distinctive Childhood Cancer Syndrome Michel De Vos, Bruce E. Hayward, Susan Picton,

An Autosomal-Recessive Form of Cutis Laxa Is Due to Homozygous Elastin Mutations, and the Phenotype May Be Modified by a Heterozygous Fibulin 5 Polymorphism

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

Matthew R. Avenarius, Michael S. Hildebrand, Yuzhou Zhang, Nicole C

Homozygous Variegate Porphyria: Identification of Mutations on Both Alleles of the Protoporphyrinogen Oxidase Gene in a Severely Affected Proband Jorge.

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,

Figure 1 Pedigree and genetic findings

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

Figure 1 Mutated CTSF in adult-onset neuronal ceroid lipofuscinosis and patients with frontotemporal dementia Mutated CTSF in adult-onset neuronal ceroid.

Clouston Syndrome Can Mimic Pachyonychia Congenita

Homozygous Missense Mutation in Fibulin-5 in an Iranian Autosomal Recessive Cutis Laxa Pedigree and Associated Haplotype Elahe Elahi, Reza Kalhor, Setareh.

Marjolijn C. J. Jongmans, Eugene T. P

Mutations in the Gene Encoding Capillary Morphogenesis Protein 2 Cause Juvenile Hyaline Fibromatosis and Infantile Systemic Hyalinosis Sandra Hanks,

Mutations in CHEK2 Associated with Prostate Cancer Risk

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

Figure 2 Compound heterozygous mutations in ADAM22

A Mutation in LIPN, Encoding Epidermal Lipase N, Causes a Late-Onset Form of Autosomal-Recessive Congenital Ichthyosis Shirli Israeli, Ziyad Khamaysi,

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,

Mapping of Small RNAs in the Human ENCODE Regions

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

A Truncating Mutation of TRAPPC9 Is Associated with Autosomal-Recessive Intellectual Disability and Postnatal Microcephaly Ganeshwaran H. Mochida, Muhammad.

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

ZNF674: A New Krüppel-Associated Box–Containing Zinc-Finger Gene Involved in Nonsyndromic X-Linked Mental Retardation Dorien Lugtenberg, Helger G. Yntema,

Presentation transcript:

Targeted Next-Generation Sequencing of a 12 Targeted Next-Generation Sequencing of a 12.5 Mb Homozygous Region Reveals ANO10 Mutations in Patients with Autosomal-Recessive Cerebellar Ataxia Sascha Vermeer, Alexander Hoischen, Rowdy P.P. Meijer, Christian Gilissen, Kornelia Neveling, Nienke Wieskamp, Arjan de Brouwer, Michel Koenig, Mathieu Anheim, Mirna Assoum, Nathalie Drouot, Slobodanka Todorovic, Vedrana Milic-Rasic, Hanns Lochmüller, Giovanni Stevanin, Cyril Goizet, Albert David, Alexandra Durr, Alexis Brice, Berry Kremer, Bart P.C. van de Warrenburg, Mascha M.V.A.P. Schijvenaars, Angelien Heister, Michael Kwint, Peer Arts, Jenny van der Wijst, Joris Veltman, Erik-Jan Kamsteeg, Hans Scheffer, Nine Knoers The American Journal of Human Genetics Volume 87, Issue 6, Pages 813-819 (December 2010) DOI: 10.1016/j.ajhg.2010.10.015 Copyright © 2010 The American Society of Human Genetics Terms and Conditions

Figure 1 Identifcation of ANO10 Mutation in the Dutch Family A with Autosomal-Recessive Cerebellar Ataxia (A) Pedigree for the Dutch family A together with the segregation of the mutation identified in this family. M1/M1 indicates homozygous carriers of the p.Leu510Arg mutation, and M1/+ indicates heterozygous carriers. The proband is indicated by an arrow. Unfortunately, DNA was not available for individual A:V.3. (B) Coverage histogram of ANO10. Upper part: Sequence-read histograms uploaded to the UCSC Genome Browser display the sequencing depth of all exons of ANO10. Tracks displayed: scale, chromosomal position, read depth histogram per bp (between 0 and 60-fold coverage; higher than 60-fold coverage is not displayed), RefSeq gene track, highly conserved elements (PhastCons Placental Mammal Conserved Elements, 28-way Multiz Alignment). Lower part: Next-generation sequencing-read coverage of ANO10 exons 8–10. Tracks displayed: scale, chromosomal position, individual 454 sequencing reads, RefSeq gene track. (C) Mutation visualization in the IGV browser. Individual reads overlapping with the mutation are displayed. Seventeen of eighteen reads show the homozygous mutation at genomic position chr3:43571913 (the reads are mapped and displayed on the + strand). (D) Verification by Sanger sequencing of missense mutation c.1529T>G (p.Leu510Arg) in ANO10 (accession number NM_018075.3). (E) Sequence comparison of ANO10 in different species. The amino acid that is mutated in the Dutch family is depicted, indicated by an arrow. The amino acid is highly conserved throughout different species, including the fruit fly. The American Journal of Human Genetics 2010 87, 813-819DOI: (10.1016/j.ajhg.2010.10.015) Copyright © 2010 The American Society of Human Genetics Terms and Conditions

Figure 2 Pedigree Structure of Two Additional Families, B and C Pedigrees for family B, from Serbia, and family C, from France, together with the segregation of the mutations identified in these families. M2/M2 indicates homozygous carriers of the p.Leu384fs mutation, and M2/+ indicates heterozygous carriers, whereas +/+ indicates individuals with two wild-type alleles. M3/M4 indicates compound-heterozygous carriers for the c.1476+1G>T and the p.Leu535X mutations, and M4/+ indicates heterozygous carriers for the p.Leu535X mutation. For family B, the degree of consanguinity is not known. Unfortunately, DNA was not available for individual C:I.1. The American Journal of Human Genetics 2010 87, 813-819DOI: (10.1016/j.ajhg.2010.10.015) Copyright © 2010 The American Society of Human Genetics Terms and Conditions

Figure 3 Expression of ANO10 in Different Human Tissues, Seen by qPCR (A) Expression of ANO10 in different adult tissues, with the highest expression seen in the brain. (B) Expression of ANO10 in different brain tissues, with the highest expression seen in the adult cerebellum and frontal and occipital cortices. The American Journal of Human Genetics 2010 87, 813-819DOI: (10.1016/j.ajhg.2010.10.015) Copyright © 2010 The American Society of Human Genetics Terms and Conditions