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

Slides:

Advertisements

Similar presentations

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

Advertisements

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

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

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

A Recurrent Mutation in PARK2 Is Associated with Familial Lung Cancer

A Missense Mutation in PRPF6 Causes Impairment of pre-mRNA Splicing and Autosomal-Dominant Retinitis Pigmentosa Goranka Tanackovic, Adriana Ransijn,

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

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

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

High-Resolution Mapping of Genotype-Phenotype Relationships in Cri du Chat Syndrome Using Array Comparative Genomic Hybridization Xiaoxiao Zhang, Antoine.

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

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.

Ali Sazci, Ph. D. , Nesrin Ercelen, M. D. , Emel Ergul, M. S

Dan Doherty, Albert E. Chudley, Gail Coghlan, Gisele E. Ishak, A

Attention-Deficit/Hyperactivity Disorder in a Population Isolate: Linkage to Loci at 4q13.2, 5q33.3, 11q22, and 17p11 Mauricio Arcos-Burgos, F. Xavier.

Philippe M. Campeau, Jaeseung C. Kim, James T. Lu, Jeremy A

Peter Ianakiev, Michael W

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

A Recurrent Missense Mutation in ZP3 Causes Empty Follicle Syndrome and Female Infertility Tailai Chen, Yuehong Bian, Xiaoman Liu, Shigang Zhao, Keliang.

Identification of a Genetic Locus for Ichthyosis Vulgaris on Chromosome 10q22.3– q24.2 Ping Liu, Qingyu Yang, Xu Wang, Aiping Feng, Tao Yang, Rong Yang,

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

Tristan F. W. McMullan, Andrew R. Collins, Anthony G. Tyers, David O

Cantú Syndrome Is Caused by Mutations in ABCC9

Genetic Background of Congenital Chloride Diarrhea in High-Incidence Populations: Finland, Poland, and Saudi Arabia and Kuwait Pia Höglund, Mari Auranen,

Hypomethylation of the H19 Gene Causes Not Only Silver-Russell Syndrome (SRS) but Also Isolated Asymmetry or an SRS-Like Phenotype Jet Bliek, Paulien.

High Incidence of Later-Onset Fabry Disease Revealed by Newborn Screening* Marco Spada, Severo Pagliardini, Makiko Yasuda, Turgut Tukel, Geetha Thiagarajan,

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

The role of sequence variations within the genes encoding collagen II, IX and XI in non- syndromic, early-onset osteoarthritis E. Jakkula, M.D., M. Melkoniemi,

Mutations in ANKRD11 Cause KBG Syndrome, Characterized by Intellectual Disability, Skeletal Malformations, and Macrodontia Asli Sirmaci, Michail Spiliopoulos,

Fatema Zahrani, Mohammed A. Aldahmesh, Muneera J. Alshammari, Selwa A

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

A Locus for Brachydactyly Type A-1 Maps to Chromosome 2q35-q36

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.

Exome Sequencing Identifies Autosomal-Dominant SRP72 Mutations Associated with Familial Aplasia and Myelodysplasia Michael Kirwan, Amanda J. Walne, Vincent.

Mutations in ECEL1 Cause Distal Arthrogryposis Type 5D

Bilineal Disease and Trans-Heterozygotes in Autosomal Dominant Polycystic Kidney Disease York Pei, Andrew D. Paterson, Kai Rong Wang, Ning He, Donna.

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

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

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

Linkage Analysis of X-linked Cone-Rod Dystrophy: Localization to Xp11

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

Next-Generation Sequencing Identifies Mutations of SMPX, which Encodes the Small Muscle Protein, X-Linked, as a Cause of Progressive Hearing Impairment

De Novo Mutations of the Gene Encoding the Histone Acetyltransferase KAT6B Cause Genitopatellar Syndrome Michael A. Simpson, Charu Deshpande, Dimitra.

Retinitis Pigmentosa and Progressive Sensorineural Hearing Loss Caused by a C12258A Mutation in the Mitochondrial MTTS2 Gene Fiona C. Mansergh, Sophia.

De Novo Truncating Mutations in AHDC1 in Individuals with Syndromic Expressive Language Delay, Hypotonia, and Sleep Apnea Fan Xia, Matthew N. Bainbridge,

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

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

Maja Hempel, Kirsten Cremer, Charlotte W. Ockeloen, Klaske D

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

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,

De Novo Nonsense Mutations in KAT6A, a Lysine Acetyl-Transferase Gene, Cause a Syndrome Including Microcephaly and Global Developmental Delay Valerie A.

A New Locus for Autosomal Recessive Hypercholesterolemia Maps to Human Chromosome 15q25-q26 Milco Ciccarese, Adolfo Pacifico, Giancarlo Tonolo, Paolo.

Volume 71, Issue 6, Pages (March 2007)

Mutations in HPSE2 Cause Urofacial Syndrome

Relative expression levels of three PTPN22 transcripts.

Mutations in CHEK2 Associated with Prostate Cancer Risk

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

PGAP2 Mutations, Affecting the GPI-Anchor-Synthesis Pathway, Cause Hyperphosphatasia with Mental Retardation Syndrome Peter M. Krawitz, Yoshiko Murakami,

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

NSD1 Mutations Are the Major Cause of Sotos Syndrome and Occur in Some Cases of Weaver Syndrome but Are Rare in Other Overgrowth Phenotypes Jenny Douglas,

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

Whole-Exome-Sequencing Identifies Mutations in Histone Acetyltransferase Gene KAT6B in Individuals with the Say-Barber-Biesecker Variant of Ohdo Syndrome

Identification and Functional Consequences of a New Mutation (E155G) in the Gene for GCAP1 That Causes Autosomal Dominant Cone Dystrophy Susan E. Wilkie,

A 22q11.2 Deletion That Excludes UFD1L and CDC45L in a Patient with Conotruncal and Craniofacial Defects Sulagna C. Saitta, James M. McGrath, Holly Mensch,

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

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

Identification and Functional Analysis of ZIC3 Mutations in Heterotaxy and Related Congenital Heart Defects Stephanie M. Ware, Jianlan Peng, Lirong Zhu,

Presentation transcript:

Dominant Mutations in KAT6A Cause Intellectual Disability with Recognizable Syndromic Features Emma Tham, Anna Lindstrand, Avni Santani, Helena Malmgren, Addie Nesbitt, Holly A. Dubbs, Elaine H. Zackai, Michael J. Parker, Francisca Millan, Kenneth Rosenbaum, Golder N. Wilson, Ann Nordgren The American Journal of Human Genetics Volume 96, Issue 3, Pages 507-513 (March 2015) DOI: 10.1016/j.ajhg.2015.01.016 Copyright © 2015 The American Society of Human Genetics Terms and Conditions

Figure 1 Facial Characteristics of the Individuals with KAT6A Mutations Individuals with KAT6A mutations show distinct facial features. Subject 2 at 22 months (A) and 9 years (B); subject 3 at 22 months (C) and 9 years (D); subject 4 at 4 months (E) and 12 months of age (F); subject 5 at 10 months (G) and 4 years 4 months of age (H); subject 6 at 5 months (I) and 3.5 years (J); and subject 7 at 17 years (K and L). There are common features in all affected individuals, e.g., bitemporal narrowing, broad nasal tip, low-set ears, thin upper lip, and/or tented mouth, although other features such as ptosis, downturned corners of the mouth, micrognathia, and smooth philtrum can only be seen in a subset of the subjects. See Table S1 for more details. The American Journal of Human Genetics 2015 96, 507-513DOI: (10.1016/j.ajhg.2015.01.016) Copyright © 2015 The American Society of Human Genetics Terms and Conditions

Figure 2 Pedigrees of the Families with KAT6A Mutations with Individual Results of Sanger Sequencing Pedigrees and KAT6A Sanger sequencing traces (A–E; with reverse strand in B) or array-CGH findings (F) in all families with KAT6A mutations. Squares denote males and circles denote females. Blackened symbols represent the affected children. The generation numbers are shown to the left and individual identification numbers are shown underneath the symbols. The American Journal of Human Genetics 2015 96, 507-513DOI: (10.1016/j.ajhg.2015.01.016) Copyright © 2015 The American Society of Human Genetics Terms and Conditions

Figure 3 Genetic Location and Functional Consequences of Detected KAT6A Mutations (A) Schematic human chromosome 8. A vertical red line indicates the position of KAT6A at 8p11.21. (B) A zoomed depiction of the KAT6A locus with a schematic illustration of exons (vertical black bars). The genetic position of all of the five KAT6A point mutations is marked by black arrows. (C) A schematic illustration of the main functional units of human KAT6A: the nuclear localization domain (H15), a double-plant homeodomain finger (PHD), a histone-acetyl-transferase domain (HAT) containing a C2H2 zinc-finger domain (light blue), and an Acetyl-coenzyme-A-binding domain (yellow); an acidic glutamate/aspartate-rich domain and a transactivation domain with both a serine-rich (red) and a methionine-rich (green) region are also shown. The truncated KAT6A forms are shown below. (D) The relative position of the truncated KAT6A in mutant mouse (MozΔ).11 The American Journal of Human Genetics 2015 96, 507-513DOI: (10.1016/j.ajhg.2015.01.016) Copyright © 2015 The American Society of Human Genetics Terms and Conditions