In-Frame Mutations in Exon 1 of SKI Cause Dominant Shprintzen-Goldberg Syndrome Virginie Carmignac, Julien Thevenon, Lesley Adès, Bert Callewaert, Sophie.

Slides:

Advertisements

Similar presentations

PIK3R1 Mutations Cause Syndromic Insulin Resistance with Lipoatrophy

Advertisements

Germline Missense Mutations Affecting KRAS Isoform B Are Associated with a Severe Noonan Syndrome Phenotype Claudio Carta, Francesca Pantaleoni, Gianfranco.

Chronic Infantile Neurological Cutaneous and Articular Syndrome Is Caused by Mutations in CIAS1, a Gene Highly Expressed in Polymorphonuclear Cells and.

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

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

Loss-of-Function Mutations in UNC45A Cause a Syndrome Associating Cholestasis, Diarrhea, Impaired Hearing, and Bone Fragility Clothilde Esteve, Ludmila.

SKIV2L Mutations Cause Syndromic Diarrhea, or Trichohepatoenteric Syndrome Alexandre Fabre, Bernard Charroux, Christine Martinez-Vinson, Bertrand Roquelaure,

A Novel Mutation and Large Size Polymorphism Affecting the V2 Domain of Keratin 1 in an African-American Family with Severe, Diffuse Palmoplantar Keratoderma.

Autosomal-Recessive Mutations in AP3B2, Adaptor-Related Protein Complex 3 Beta 2 Subunit, Cause an Early-Onset Epileptic Encephalopathy with Optic Atrophy

Mutations in FLVCR2 Are Associated with Proliferative Vasculopathy and Hydranencephaly-Hydrocephaly Syndrome (Fowler Syndrome) Esther Meyer, Christopher.

Biallelic Loss of Proprioception-Related PIEZO2 Causes Muscular Atrophy with Perinatal Respiratory Distress, Arthrogryposis, and Scoliosis Andrea Delle.

Mutations in the Transcription Factor Gene SOX18 Underlie Recessive and Dominant Forms of Hypotrichosis-Lymphedema-Telangiectasia Alexandre Irrthum,

Mutation Altering the miR-184 Seed Region Causes Familial Keratoconus with Cataract Anne E. Hughes, Declan T. Bradley, Malcolm Campbell, Judith Lechner,

Novel mutations and polymorphisms in the CFTR gene associated with three subtypes of congenital absence of vas deferens Xiaojian Yang, M.D., Qipeng Sun,

Mutations in Histone Acetylase Modifier BRPF1 Cause an Autosomal-Dominant Form of Intellectual Disability with Associated Ptosis Francesca Mattioli,

Identification of a Novel BBS Gene (BBS12) Highlights the Major Role of a Vertebrate- Specific Branch of Chaperonin-Related Proteins in Bardet-Biedl Syndrome

Eija Siintola, Meral Topcu, Nina Aula, Hannes Lohi, Berge A

Mosaicism for a KITLG Mutation in Linear and Whorled Nevoid Hypermelanosis Arthur Sorlin, Annabel Maruani, Marie-Hélène Aubriot-Lorton, Paul Kuentz, Yannis.

Recessive Mutations in POLR3B, Encoding the Second Largest Subunit of Pol III, Cause a Rare Hypomyelinating Leukodystrophy Martine Tétreault, Karine.

HOPX: The Unusual Homeodomain-Containing Protein

Syndrome of Hepatic Cirrhosis, Dystonia, Polycythemia, and Hypermanganesemia Caused by Mutations in SLC30A10, a Manganese Transporter in Man Karin Tuschl,

PIK3R1 Mutations Cause Syndromic Insulin Resistance with Lipoatrophy

Mutations in KCTD1 Cause Scalp-Ear-Nipple Syndrome

Mutations in ZDHHC9, Which Encodes a Palmitoyltransferase of NRAS and HRAS, Cause X-Linked Mental Retardation Associated with a Marfanoid Habitus F.

De Novo Loss-of-Function Mutations in SETD5, Encoding a Methyltransferase in a 3p25 Microdeletion Syndrome Critical Region, Cause Intellectual Disability

RSPO4 Is the Major Gene in Autosomal-Recessive Anonychia and Mutations Cluster in the Furin-Like Cysteine-Rich Domains of the Wnt Signaling Ligand R-spondin.

Mutations in EZH2 Cause Weaver Syndrome

Variants in HNRNPH2 on the X Chromosome Are Associated with a Neurodevelopmental Disorder in Females Jennifer M. Bain, Megan T. Cho, Aida Telegrafi,

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

Exome Sequencing Identifies SLCO2A1 Mutations as a Cause of Primary Hypertrophic Osteoarthropathy Zhenlin Zhang, Weibo Xia, Jinwei He, Zeng Zhang, Yaohua.

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

Germline Mutations of the Paired–Like Homeobox 2B (PHOX2B) Gene in Neuroblastoma Delphine Trochet, Franck Bourdeaut, Isabelle Janoueix-Lerosey, Anne.

Peter Ianakiev, Michael W

Capillary Malformation–Arteriovenous Malformation, a New Clinical and Genetic Disorder Caused by RASA1 Mutations Iiro Eerola, Laurence M. Boon, John.

Frontorhiny, a Distinctive Presentation of Frontonasal Dysplasia Caused by Recessive Mutations in the ALX3 Homeobox Gene Stephen R.F. Twigg, Sarah L.

NRAS, NRAS, Which Mutation Is Fairest of Them All?

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

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

Volume 64, Issue 5, Pages (November 2003)

RBPJ Mutations Identified in Two Families Affected by Adams-Oliver Syndrome Susan J. Hassed, Graham B. Wiley, Shaofeng Wang, Ji-Yun Lee, Shibo Li, Weihong.

Mutations in SLC13A5 Cause Autosomal-Recessive Epileptic Encephalopathy with Seizure Onset in the First Days of Life Julien Thevenon, Mathieu Milh, François.

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

Mutations in the DBP-Deficiency Protein HSD17B4 Cause Ovarian Dysgenesis, Hearing Loss, and Ataxia of Perrault Syndrome Sarah B. Pierce, Tom Walsh, Karen.

Ataxia with Isolated Vitamin E Deficiency: Heterogeneity of Mutations and Phenotypic Variability in a Large Number of Families Laurent Cavalier, Karim.

Mutations in ZDHHC9, Which Encodes a Palmitoyltransferase of NRAS and HRAS, Cause X-Linked Mental Retardation Associated with a Marfanoid Habitus F.

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

Characterization of a Germline Mosaicism in Families with Lowe Syndrome, and Identification of Seven Novel Mutations in the OCRL1 Gene Véronique Satre,

Nadja Ehmke, Almuth Caliebe, Rainer Koenig, Sarina G

Deletion of PREPL, a Gene Encoding a Putative Serine Oligopeptidase, in Patients with Hypotonia-Cystinuria Syndrome Jaak Jaeken, Kevin Martens, Inge.

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

Mutations in Endothelin 1 Cause Recessive Auriculocondylar Syndrome and Dominant Isolated Question-Mark Ears Christopher T. Gordon, Florence Petit, Peter M.

L. Aravind, Eugene V. Koonin Current Biology

Volume 14, Issue 4, Pages (April 2006)

X-Linked Dominant Scapuloperoneal Myopathy Is Due to a Mutation in the Gene Encoding Four-and-a-Half-LIM Protein 1 Catarina M. Quinzii, Tuan H. Vu, K.

Microphthalmia-Associated Transcription Factor (MITF): Multiplicity in Structure, Function, and Regulation Shigeki Shibahara, Kazuhisa Takeda, Ken-ichi.

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

Mutation Analysis of the Entire PKD1 Gene: Genetic and Diagnostic Implications Sandro Rossetti, Lana Strmecki, Vicki Gamble, Sarah Burton, Vicky Sneddon,

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

Missense Mutation in Pseudouridine Synthase 1 (PUS1) Causes Mitochondrial Myopathy and Sideroblastic Anemia (MLASA) Yelena Bykhovskaya, Kari Casas, Emebet.

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

Effect of Mutation Type and Location on Clinical Outcome in 1,013 Probands with Marfan Syndrome or Related Phenotypes and FBN1 Mutations: An International.

Figure 1 Schematic of the OPA3 gene and OPA3 protein isoform b

Mutations in PRPS1, Which Encodes the Phosphoribosyl Pyrophosphate Synthetase Enzyme Critical for Nucleotide Biosynthesis, Cause Hereditary Peripheral.

Volume 78, Issue 2, Pages (July 2010)

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

Mutations in NEXN, a Z-Disc Gene, Are Associated with Hypertrophic Cardiomyopathy Hu Wang, Zhaohui Li, Jizheng Wang, Kai Sun, Qiqiong Cui, Lei Song, Yubao.

Cole-Carpenter Syndrome Is Caused by a Heterozygous Missense Mutation in P4HB Frank Rauch, Somayyeh Fahiminiya, Jacek Majewski, Jian Carrot-Zhang, Sergei.

A Major Determinant for Binding and Aminoacylation of tRNAAla in Cytoplasmic Alanyl- tRNA Synthetase Is Mutated in Dominant Axonal Charcot-Marie-Tooth.

Neurodegenerative Tauopathies

Mutations in Histone Acetylase Modifier BRPF1 Cause an Autosomal-Dominant Form of Intellectual Disability with Associated Ptosis Francesca Mattioli,

Presentation transcript:

In-Frame Mutations in Exon 1 of SKI Cause Dominant Shprintzen-Goldberg Syndrome Virginie Carmignac, Julien Thevenon, Lesley Adès, Bert Callewaert, Sophie Julia, Christel Thauvin-Robinet, Lucie Gueneau, Jean-Benoit Courcet, Estelle Lopez, Katherine Holman, Marjolijn Renard, Henri Plauchu, Ghislaine Plessis, Julie De Backer, Anne Child, Gavin Arno, Laurence Duplomb, Patrick Callier, Bernard Aral, Pierre Vabres, Nadège Gigot, Eloisa Arbustini, Maurizia Grasso, Peter N. Robinson, Cyril Goizet, Clarisse Baumann, Maja Di Rocco, Jaime Sanchez Del Pozo, Frédéric Huet, Guillaume Jondeau, Gwenaëlle Collod- Beroud, Christophe Beroud, Jeanne Amiel, Valérie Cormier-Daire, Jean-Baptiste Rivière, Catherine Boileau, Anne De Paepe, Laurence Faivre The American Journal of Human Genetics Volume 91, Issue 5, Pages 950-957 (November 2012) DOI: 10.1016/j.ajhg.2012.10.002 Copyright © 2012 The American Society of Human Genetics Terms and Conditions

Figure 1 Clinical Presentations and Pedigrees of Subjects with SGS and Mutations in SKI (A) Photographs of affected individual II-1 (from family 2), who has a SKI de novo c.94C>G variant. Note the hypertelorism, proptosis, downslanting palpebral fissures, maxillary and mandibular hypoplasia, low-set ears (Aa–Ac), joint contractures (Ad), arachnodactyly and camptodactyly (Ae), deformed feet (Af–Ag), severe scoliosis (Ah), translucent skin (Ai), and hypertrophy of the palatal shelves (Aj). (B) Photographs of affected individual 14 (family 8), who has a SKI de novo c.103C>T variant. Note the dysmorphic features in favor of SGS (Ba–Bb), severe pectus carinatum (Bc), arachnodactyly, and camptodactyly (Bd). (C) Photographs of affected individual III-4 (from family 3), who has a c.280_291delTCCGACCGCTCC variant in exon 1 of SKI. Note the dysmorphic features and habitus in favor of SGS (Ca, Cc, and Cd), foot deformity (Cb), and hand deformity with camptodactyly (Ce). (D) Photographs of affected individual IV-2 from family 3 (child of individual III-4 in C). (E) Pedigrees of families 1 (F1), 2 (F2), 3 (F3), and 4 (F4) studied by exome sequencing. Individuals studied are shown by an arrow. The American Journal of Human Genetics 2012 91, 950-957DOI: (10.1016/j.ajhg.2012.10.002) Copyright © 2012 The American Society of Human Genetics Terms and Conditions

Figure 2 Location of SGS-Associated Mutations in SKI (A) Schematic representation of the seven coding exons of SKI (top). The 5′ and 3′ UTRs are denoted in light gray. Exon 1 encodes the N-terminal R-SMAD- and SMAD- binding domains (blue and red box, respectively, at the bottom) and the DHD domain (purple box), and the remaining exons encode the C terminus with its two coiled-coil domains (green boxes at the bottom). Sites for interaction with N-CoR and mSin3 are also shown as light blue and dark blue lines, respectively. All mutations (asterisks for missense variants and lines for deletions) are located in the R-SMAD binding domain. (B) Highly conserved amino acid residues (indicated in dark boxes) are conserved in vertebrates. All mutations affect highly conserved residues. The following abbreviations are used: Hs, Homo sapiens; Ms, Mus musculus; Cf, Canis familiaris; Bt, Bos Taurus; Mac, Macropus eugeneii; Gg, Gorilla gorilla; and Dr, Danio rerio. The American Journal of Human Genetics 2012 91, 950-957DOI: (10.1016/j.ajhg.2012.10.002) Copyright © 2012 The American Society of Human Genetics Terms and Conditions

Figure 3 Three-Dimensional Modeling of SKI (A) Functional domains of wild-type protein composed of an N-terminal DNA transcriptional regulating domain (dark blue) including R-SMAD (light blue) and DHD domains, a central SMAD4-interacting domain (greenish yellow), and a C-terminal coiled-coil domain (red). (B) Enlargement of the region affected by all the mutations. The in-frame deletions shorten a loop (between residues 92 and 97). The missense mutations disrupt a flexible region (residues 31–35). All the mutations are localized on the same surface of the R-SMAD-binding domain. The American Journal of Human Genetics 2012 91, 950-957DOI: (10.1016/j.ajhg.2012.10.002) Copyright © 2012 The American Society of Human Genetics Terms and Conditions