Whole-Genome Analysis Reveals that Mutations in Inositol Polyphosphate Phosphatase-like 1 Cause Opsismodysplasia Jennifer E. Below, Dawn L. Earl, Kathryn M.

Slides:

Advertisements

Similar presentations

Previous Estimates of Mitochondrial DNA Mutation Level Variance Did Not Account for Sampling Error: Comparing the mtDNA Genetic Bottleneck in Mice and.

Advertisements

Connexin Mutations in Skin Disease and Hearing Loss David P. Kelsell, Wei-Li Di, Mark J. Houseman The American Journal of Human Genetics Volume 68, Issue.

Functional Analysis of the Neurofibromatosis Type 2 Protein by Means of Disease- Causing Point Mutations Renee P. Stokowski, David R. Cox The American.

Autosomal-Dominant Multiple Pterygium Syndrome Is Caused by Mutations in MYH3 Jessica X. Chong, Lindsay C. Burrage, Anita E. Beck, Colby T. Marvin, Margaret.

PRIMUS: Rapid Reconstruction of Pedigrees from Genome-wide Estimates of Identity by Descent Jeffrey Staples, Dandi Qiao, Michael H. Cho, Edwin K. Silverman,

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

The Primordial Growth Disorder 3-M Syndrome Connects Ubiquitination to the Cytoskeletal Adaptor OBSL1 Dan Hanson, Philip G. Murray, Amit Sud, Samia A.

Identification of a Frameshift Mutation in Osterix in a Patient with Recessive Osteogenesis Imperfecta Pablo Lapunzina, Mona Aglan, Samia Temtamy, José.

Mutations in the Beta Propeller WDR72 Cause Autosomal-Recessive Hypomaturation Amelogenesis Imperfecta Walid El-Sayed, David A. Parry, Roger C. Shore,

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

Exome Sequencing Identifies PDE4D Mutations in Acrodysostosis

Mutations in WNT7A Cause a Range of Limb Malformations, Including Fuhrmann Syndrome and Al-Awadi/Raas-Rothschild/Schinzel Phocomelia Syndrome C.G. Woods,

Inactivating Mutations in ESCO2 Cause SC Phocomelia and Roberts Syndrome: No Phenotype-Genotype Correlation Birgitt Schüle, Angelica Oviedo, Kathreen.

Margaret J. McMillin, Anita E. Beck, Jessica X. Chong, Kathryn M

Jacquelyn Bond, Sheila Scott, Daniel J

Mutations in KCTD1 Cause Scalp-Ear-Nipple Syndrome

A Novel Skeletal Dysplasia with Developmental Delay and Acanthosis Nigricans Is Caused by a Lys650Met Mutation in the Fibroblast Growth Factor Receptor.

Kenneth E. White, Jose M. Cabral, Siobhan I

Michael Field, Patrick S

Mutations in EZH2 Cause Weaver Syndrome

Mutations in PCYT1A, Encoding a Key Regulator of Phosphatidylcholine Metabolism, Cause Spondylometaphyseal Dysplasia with Cone-Rod Dystrophy Julie Hoover-Fong,

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

Haploinsufficiency of SF3B4, a Component of the Pre-mRNA Spliceosomal Complex, Causes Nager Syndrome Francois P. Bernier, Oana Caluseriu, Sarah Ng, Jeremy.

Mutations in DDR2 Gene Cause SMED with Short Limbs and Abnormal Calcifications Ruth Bargal, Valerie Cormier-Daire, Ziva Ben-Neriah, Martine Le Merrer,

A Multicolor FISH Assay Does Not Detect DUP25 in Control Individuals or in Reported Positive Control Cells Yanina Weiland, Jürgen Kraus, Michael R. Speicher

Exome Sequencing Identifies INPPL1 Mutations as a Cause of Opsismodysplasia Céline Huber, Eissa Ali Faqeih, Deborah Bartholdi, Christine Bole-Feysot,

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

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

Transcriptional Consequences of 16p11

Mutations in the Gene Encoding the RER Protein FKBP65 Cause Autosomal-Recessive Osteogenesis Imperfecta Yasemin Alanay, Hrispima Avaygan, Natalia Camacho,

Recessive Inactivating Mutations in TBCK, Encoding a Rab GTPase-Activating Protein, Cause Severe Infantile Syndromic Encephalopathy Jessica X. Chong,

De Novo Mutations in MLL Cause Wiedemann-Steiner Syndrome

SAMS, a Syndrome of Short Stature, Auditory-Canal Atresia, Mandibular Hypoplasia, and Skeletal Abnormalities Is a Unique Neurocristopathy Caused by Mutations.

AZFc Deletions and Spermatogenic Failure: A Population-Based Survey of 20,000 Y Chromosomes Steven G. Rozen, Janet D. Marszalek, Kathryn Irenze, Helen.

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

Bent Bone Dysplasia-FGFR2 type, a Distinct Skeletal Disorder, Has Deficient Canonical FGF Signaling Amy E. Merrill, Anna Sarukhanov, Pavel Krejci, Brian.

Shyam S. Jayaraman, David J. Rayhan, Salar Hazany, Michael S. Kolodney

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

Hypermethylation of the CpG Island Near the G4C2 Repeat in ALS with a C9orf72 Expansion Zhengrui Xi, Lorne Zinman, Danielle Moreno, Jennifer Schymick,

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

Mutations in the Gene Encoding the Calcium-Permeable Ion Channel TRPV4 Produce Spondylometaphyseal Dysplasia, Kozlowski Type and Metatropic Dysplasia

Mutations in the Gene Encoding the Calcium-Permeable Ion Channel TRPV4 Produce Spondylometaphyseal Dysplasia, Kozlowski Type and Metatropic Dysplasia

Dominant Mutations in KAT6A Cause Intellectual Disability with Recognizable Syndromic Features Emma Tham, Anna Lindstrand, Avni Santani, Helena Malmgren,

Erratum The American Journal of Human Genetics

Mutations in ECEL1 Cause Distal Arthrogryposis Type 5D

Guilherme L. Yamamoto, Wagner A. R. Baratela, Tatiana F

M. Bamshad, T. Le, W. S. Watkins, M. E. Dixon, B. E. Kramer, A. D

Ryan McDaniell, Daniel M. Warthen, Pedro A

Multicentric Carpotarsal Osteolysis Is Caused by Mutations Clustering in the Amino- Terminal Transcriptional Activation Domain of MAFB Andreas Zankl,

The Primordial Growth Disorder 3-M Syndrome Connects Ubiquitination to the Cytoskeletal Adaptor OBSL1 Dan Hanson, Philip G. Murray, Amit Sud, Samia A.

Characterization and Mutation Analysis of Human LEFTY A and LEFTY B, Homologues of Murine Genes Implicated in Left-Right Axis Development K. Kosaki,

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.

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

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

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

GGC Repeat Expansion and Exon 1 Methylation of XYLT1 Is a Common Pathogenic Variant in Baratela-Scott Syndrome Amy J. LaCroix, Deborah Stabley, Rebecca.

Mutations in CHEK2 Associated with Prostate Cancer Risk

Type and Level of RMRP Functional Impairment Predicts Phenotype in the Cartilage Hair Hypoplasia–Anauxetic Dysplasia Spectrum Christian T. Thiel, Geert.

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

Frances R. Goodman, Chiara Bacchelli, Angela F. Brady, Louise A

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

Ciliary Abnormalities Due to Defects in the Retrograde Transport Protein DYNC2H1 in Short-Rib Polydactyly Syndrome Amy E. Merrill, Barry Merriman, Claire.

Marshall Syndrome Associated with a Splicing Defect at the COL11A1 Locus Andrew J. Griffith, Leslie K. Sprunger, D. Alexa Sirko-Osadsa, George E. Tiller,

Hannah R. Elliott, David C. Samuels, James A. Eden, Caroline L

Familial Isolated Clubfoot Is Associated with Recurrent Chromosome 17q23.1q23.2 Microduplications Containing TBX4 David M. Alvarado, Hyuliya Aferol,

Examining Variation in Recombination Levels in the Human Female: A Test of the Production-Line Hypothesis Ross Rowsey, Jennifer Gruhn, Karl W. Broman,

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,

Heterozygous RNF13 Gain-of-Function Variants Are Associated with Congenital Microcephaly, Epileptic Encephalopathy, Blindness, and Failure to Thrive

Presentation transcript:

Whole-Genome Analysis Reveals that Mutations in Inositol Polyphosphate Phosphatase-like 1 Cause Opsismodysplasia Jennifer E. Below, Dawn L. Earl, Kathryn M. Shively, Margaret J. McMillin, Joshua D. Smith, Emily H. Turner, Mark J. Stephan, Lihadh I. Al-Gazali, Jozef L. Hertecant, David Chitayat, Sheila Unger, Daniel H. Cohn, Deborah Krakow, James M. Swanson, Elaine M. Faustman, Jay Shendure, Deborah A. Nickerson, Michael J. Bamshad The American Journal of Human Genetics Volume 92, Issue 1, Pages 137-143 (January 2013) DOI: 10.1016/j.ajhg.2012.11.011 Copyright © 2013 The American Society of Human Genetics Terms and Conditions

Figure 1 Characteristic Physical Findings in Children and Adults with Opsismodysplasia (A–D) Typical features of the face include relative macrocephaly, a prominent forehead, and a short nose with a depressed nasal bridge. (E and F) Acquired abnormalities resulting from undermineralization of the long bones include bowing of the upper limb (E) and/or lower limb (F). Case identifiers: AII-1 (A, E, F), AII-2 (B), FII-1 (C), and FII-2 (D), corresponding to those in Table 1, where a detailed description of each individual is provided. The American Journal of Human Genetics 2013 92, 137-143DOI: (10.1016/j.ajhg.2012.11.011) Copyright © 2013 The American Society of Human Genetics Terms and Conditions

Figure 2 Radiographs of Individual AII-1 at 2 Years and 11 Months of Age (A) Lateral image of skull showing midface hypoplasia and underdevelopment of the maxilla. (B) Anterior-posterior (AP) image of the pelvis showing decreased mineralization, dislocated hips, poorly formed acetabula, and loss of normal architecture of the proximal femurs. (C and E) AP image of the chest notable for under mineralization of the vertebrae and platyspondyly. (D) The metacarus, metatarsus, and all of the phalanges are short and irregular with flared metaphyses. (F and G) Delayed mineralization and absence of growth centers in the upper (F) and lower (G) limbs. The American Journal of Human Genetics 2013 92, 137-143DOI: (10.1016/j.ajhg.2012.11.011) Copyright © 2013 The American Society of Human Genetics Terms and Conditions

Figure 3 Genomic Structure and Allelic Spectrum of INPPL1 Mutations that Cause Opsismodysplasia INPPL1 is composed of 28 exons that encode untranslated regions (orange) and protein coding sequence (blue) domains including SH2 (red), catalytic (yellow), a proline-rich region (orange), ubiquitin-interacting region (light blue), and SAM (green). Arrows indicate the locations of nine different mutations found in seven families with opsismodysplasia. Inverted hatch mark indicates recurrent mutation. The American Journal of Human Genetics 2013 92, 137-143DOI: (10.1016/j.ajhg.2012.11.011) Copyright © 2013 The American Society of Human Genetics Terms and Conditions