Centre for Arab Genomic Studies a Division of Sheikh Hamdan Award for Medical Sciences

Total Page：16

File Type：pdf, Size：1020Kb

Centre for Arab Genomic Studies A Division of Sheikh Hamdan Award for Medical Sciences The atalogue for ransmission enetics in rabs C T G A CTGA Database Membrane-Type Frizzled-Related Protein Alternative Names The protein encoded by the gene is made up of 579 MFRP amino acids and is approximately 62 kDa in size. Based on the amino acid sequence, the protein has Record Category been shown to contain regions with similarities to Gene locus the cysteine-rich domain (CRD) of frizzled protein and the CUB domain found in proteins such as WHO-ICD complement subcomponent C1r/C1s, Uegf and N/A to gene loci bone morphogenetic protein-1. More than a dozen mutations, both homozygous and compound Incidence per 100,000 Live Births heterozygous, have been linked to microphthalmia, N/A to gene loci isolated 5 and nanophthalmos 2. OMIM Number Epidemiology in the Arab World 606227 Saudi Arabia Mode of Inheritance N/A to gene loci Nowilaty et al. (2013) carried out a genetic analysis of posterior microphthalmia affected individuals. A Gene Map Locus total of 24 patients were studied. A novel 11q23.3 homozygous truncating mutation, c.666dup (p.T223HfsX16), was discovered in the MFRP gene Description in one patient. The authors noted that there were no The MFRP gene encodes a protein belonging to the clinical differences between patients carrying frizzled-related protein family. The protein is an MFRP mutations, PRSS56 mutations, or no integral component of the apical plasma membrane. detected mutations. Based on studies in other species, the protein is believed to be involved in the biological processes References of photoreceptor cell development and retinal Nowilaty SR, Khan AO, Aldahmesh MA, Tabbara development. KF, Al-Amri A, Alkuraya FS. Biometric and molecular characterization of clinically diagnosed The MFRP gene is associated with two ocular posterior microphthalmos. Am J Ophthalmol. 2013; disorders: microphthalmia, isolated 5 and 155(2):361-372.e7. PMID: 23127749 nanophthalmos 2. Microphthalmia is a congenital disorder where one or both eyeballs are abnormally Related CTGA Records small. Nanophthalmos, also called pure or total Microphthalmia, Isolated 5 microphthalmos, is characterized by a small eye, extreme hyperopia and a high incidence of angle- External Links closure glaucoma. https://www.genecards.org/cgi- bin/carddisp.pl?gene=MFRP Molecular Genetics The MFRP gene, located on the long arm of Contributors chromosome 11, is about 7.7 kb in length. Its Sayeeda Hana: 24.8.2016 coding sequence is made up of 15 exons. The C1QTNF5 gene (C1q- and Tumor Necrosis Factor- Related Protein 5), a retina-specific collagen gene, is located within the 3’ untranslated region of exon 13 of MFRP and hence both genes are expressed as a bicistronic transcript. Levels of expression are highest in the Retinal Pigment Epithelium and the ciliary body. Copyright © Centre for Arab Genomic Studies 2 .

Copy Link

Recommended publications

Natural Mutations Affect Structure and Function of Gc1q Domain of Otolin-1
International Journal of Molecular Sciences Article Natural Mutations Affect Structure and Function of gC1q Domain of Otolin-1 Rafał Hołubowicz * , Andrzej Ozyhar˙ and Piotr Dobryszycki * Department of Biochemistry, Molecular Biology and Biotechnology, Faculty of Chemistry, Wrocław University of Science and Technology, Wybrzeze˙ Wyspia´nskiego27, 50-370 Wrocław, Poland; [email protected] * Correspondence: [email protected] (R.H.); [email protected] (P.D.); Tel.: +48-71-320-63-34 (R.H.); +48-71-320-63-32 (P.D.) Abstract: Otolin-1 is a scaffold protein of otoliths and otoconia, calcium carbonate biominerals from the inner ear. It contains a gC1q domain responsible for trimerization and binding of Ca2+. Knowl- edge of a structure–function relationship of gC1q domain of otolin-1 is crucial for understanding the biology of balance sensing. Here, we show how natural variants alter the structure of gC1q otolin-1 and how Ca2+ are able to revert some effects of the mutations. We discovered that natural substitutions: R339S, R342W and R402P negatively affect the stability of apo-gC1q otolin-1, and that Q426R has a stabilizing effect. In the presence of Ca2+, R342W and Q426R were stabilized at higher Ca2+ concentrations than the wild-type form, and R402P was completely insensitive to Ca2+. The mutations affected the self-association of gC1q otolin-1 by inducing detrimental aggregation (R342W) or disabling the trimerization (R402P) of the protein. Our results indicate that the natural variants of gC1q otolin-1 may have a potential to cause pathological changes in otoconia and otoconial membrane, which could affect sensing of balance and increase the probability of occurrence of benign Citation: Hołubowicz, R.; Ozyhar,˙ paroxysmal positional vertigo (BPPV).
[Show full text]
Common MFRP Sequence Variants Are Not Associated with Moderate to High Hyperopia, Isolated Microphthalmia, and High Myopia
Molecular Vision 2008; 14:387-393 <http://www.molvis.org/molvis/v14/a47> © 2008 Molecular Vision Received 12 December 2007 | Accepted 6 February 2008 | Published 4 March 2008 Common MFRP sequence variants are not associated with moderate to high hyperopia, isolated microphthalmia, and high myopia Ravikanth Metlapally,1,2 Yi-Ju Li,2 Khanh-Nhat Tran-Viet,2 Anuradha Bulusu,2 Tristan R. White,2 Jaclyn Ellis, 2 Daniel Kao,2 Terri L. Young1,2 1Duke University Eye Center, Durham, NC; 2Duke University Center for Human Genetics, Durham, NC Purpose: The membrane-type frizzled-related protein (MFRP) gene is selectively expressed in the retinal pigment epithelium and ciliary body, and mutations of this gene cause nanophthalmos. The MFRP gene may not be essential for retinal function but has been hypothesized to play a role in ocular axial length regulation. The involvement of the MFRP gene in moderate to high hyperopic, isolated microphthalmic/anophthalmic, and high myopic patients was tested in two phases: a mutation screening/sequence variant discovery phase and a genetic association study phase. Methods: Eleven hyperopic, ten microphthalmic/anophthalmic, and seven non-syndromic high-grade myopic patients of varying ages and 11 control subjects participated in the mutation screening phase. Sixteen primer pairs were designed to amplify the 13 exons of the MFRP gene including intron/exon boundaries. Polymerase chain reactions were performed, and amplified products were sequenced using standard techniques. Normal and affected individual DNA sequences were compared alongside the known reference sequence (UCSC genome browser) for the MFRP gene. The genetic association study included 146 multiplex non-syndromic high-grade myopia families.
[Show full text]
The Genetic and Clinical Landscape of Nanophthalmos in an Australian
medRxiv preprint doi: https://doi.org/10.1101/19013599; this version posted December 4, 2019. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC 4.0 International license . 1 The genetic and clinical landscape of nanophthalmos in an Australian cohort 2 3 Running title: Genetics of nanophthalmos in Australia 4 5 Owen M Siggs1, Mona S Awadalla1, Emmanuelle Souzeau1, Sandra E Staffieri2,3,4, Lisa S Kearns2, Kate 6 Laurie1, Abraham Kuot1, Ayub Qassim1, Thomas L Edwards2, Michael A Coote2, Erica Mancel5, Mark J 7 Walland6, Joanne Dondey7, Anna Galanopoulous8, Robert J Casson8, Richard A Mills1, Daniel G 8 MacArthur9,10, Jonathan B Ruddle2,3,4, Kathryn P Burdon1,11, Jamie E Craig1 9 10 1Department of Ophthalmology, Flinders University, Adelaide, Australia 11 2Centre for Eye Research Australia, Royal Victorian Eye and Ear Hospital, Melbourne, Australia 12 3Department of Ophthalmology, University of Melbourne, Melbourne, Australia 13 4Department of Ophthalmology, Royal Children’s Hospital, Melbourne, Australia 14 5Centre Hospitalier Territorial de Nouvelle-Calédonie, Noumea, New Caledonia 15 6Glaucoma Investigation and Research Unit, Royal Victorian Eye and Ear Hospital, Melbourne, Australia 16 7Royal Victorian Eye and Ear Hospital, Melbourne, Australia 17 8Discipline of Ophthalmology & Visual Sciences, University of Adelaide, Adelaide, Australia 18 9Program in Medical and Population
[Show full text]
Identification of Potential Key Genes and Pathway Linked with Sporadic Creutzfeldt-Jakob Disease Based on Integrated Bioinformatics Analyses
medRxiv preprint doi: https://doi.org/10.1101/2020.12.21.20248688; this version posted December 24, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission. Identification of potential key genes and pathway linked with sporadic Creutzfeldt-Jakob disease based on integrated bioinformatics analyses Basavaraj Vastrad1, Chanabasayya Vastrad*2 , Iranna Kotturshetti 1. Department of Biochemistry, Basaveshwar College of Pharmacy, Gadag, Karnataka 582103, India. 2. Biostatistics and Bioinformatics, Chanabasava Nilaya, Bharthinagar, Dharwad 580001, Karanataka, India. 3. Department of Ayurveda, Rajiv Gandhi Education Society`s Ayurvedic Medical College, Ron, Karnataka 562209, India. * Chanabasayya Vastrad [email protected] Ph: +919480073398 Chanabasava Nilaya, Bharthinagar, Dharwad 580001 , Karanataka, India NOTE: This preprint reports new research that has not been certified by peer review and should not be used to guide clinical practice. medRxiv preprint doi: https://doi.org/10.1101/2020.12.21.20248688; this version posted December 24, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission. Abstract Sporadic Creutzfeldt-Jakob disease (sCJD) is neurodegenerative disease also called prion disease linked with poor prognosis. The aim of the current study was to illuminate the underlying molecular mechanisms of sCJD. The mRNA microarray dataset GSE124571 was downloaded from the Gene Expression Omnibus database. Differentially expressed genes (DEGs) were screened.
[Show full text]
Adiponectin and Related C1q/TNF-Related Proteins Bind Selectively to Anionic Phospholipids and Sphingolipids
Adiponectin and related C1q/TNF-related proteins bind selectively to anionic phospholipids and sphingolipids Jessica J. Yea,b, Xin Bianc,d, Jaechul Lima,b, and Ruslan Medzhitova,b,1 aHHMI, Yale University, New Haven, CT 06520; bDepartment of Immunobiology, Yale University School of Medicine, New Haven, CT 06520; cDepartment of Cell Biology, Yale University School of Medicine, New Haven, CT 06520; and dDepartment of Neuroscience, Yale University School of Medicine, New Haven, CT 06520 Contributed by Ruslan Medzhitov, April 14, 2020 (sent for review December 20, 2019; reviewed by Ido Amit and G. William Wong) Adiponectin (Acrp30) is an adipokine associated with protection 5-mers of trimers, respectively referred to as low molecular weight from cardiovascular disease, insulin resistance, and inflammation. (LMW), medium molecular weight (MMW), and high molecular Although its effects are conventionally attributed to binding weight (HMW) complexes. Adiponectin can also be cleaved by Adipor1/2 and T-cadherin, its abundance in circulation, role in serum elastases and thrombin between the globular C1q-like head ceramide metabolism, and homology to C1q suggest an overlooked domain and the collagenous tail domain, forming globular adi- role as a lipid-binding protein, possibly generalizable to other C1q/ ponectin (gAd). While gAd appears to bind AdipoR1/2 and ac- TNF-related proteins (CTRPs) and C1q family members. To investi- tivate AMPK more strongly than full-length protein (19, 20), levels gate this, adiponectin, representative family members, and variants of HMW multimers are more strongly associated with insulin were expressed in Expi293 cells and tested for binding to lipids in sensitivity (21, 22), have a longer half-life in circulation (18), and liposomes using density centrifugation.
[Show full text]
The Sole Lsm Complex in Cyanidioschyzon Merolae Associates with Pre-Mrna Splicing and Mrna Degradation Factors
Downloaded from rnajournal.cshlp.org on May 17, 2017 - Published by Cold Spring Harbor Laboratory Press The sole LSm complex in Cyanidioschyzon merolae associates with pre-mRNA splicing and mRNA degradation factors KIRSTEN A. REIMER,1,9 MARTHA R. STARK,1 LISBETH-CAROLINA AGUILAR,2 SIERRA R. STARK,1 ROBERT D. BURKE,3 JACK MOORE,4 RICHARD P. FAHLMAN,4,5 CALVIN K. YIP,6 HARUKO KUROIWA,7 MARLENE OEFFINGER,2,8 and STEPHEN D. RADER1 1Department of Chemistry, University of Northern British Columbia, Prince George, BC V2N 4Z9, Canada 2Laboratory of RNP Biochemistry, Institut de Recherches Cliniques de Montréal (IRCM), Faculty of Medicine, McGill University, Montreal, QC H3A 0G4, Canada 3Department of Biochemistry and Microbiology, University of Victoria, Victoria, BC, V8W 3P6, Canada 4Department of Biochemistry, University of Alberta, Edmonton, Alberta T6G 2H7, Canada 5Department of Oncology, University of Alberta, Edmonton, Alberta T6G 2H7, Canada 6Department of Biochemistry and Molecular Biology, The University of British Columbia, Vancouver, BC V6T 1Z3, Canada 7Kuroiwa Initiative Research Unit, College of Science, Rikkyo University, Toshima, Tokyo 171-8501, Japan 8Département de Biochimie, Université de Montréal, Montréal, QC H2W 1R7, Canada ABSTRACT Proteins of the Sm and Sm-like (LSm) families, referred to collectively as (L)Sm proteins, are found in all three domains of life and are known to promote a variety of RNA processes such as base-pair formation, unwinding, RNA degradation, and RNA stabilization. In eukaryotes, (L)Sm proteins have been studied, inter alia, for their role in pre-mRNA splicing. In many organisms, the LSm proteins form two distinct complexes, one consisting of LSm1–7 that is involved in mRNA degradation in the cytoplasm, and the other consisting of LSm2–8 that binds spliceosomal U6 snRNA in the nucleus.
[Show full text]
Research Article Mouse Model Resources for Vision Research
Hindawi Publishing Corporation Journal of Ophthalmology Volume 2011, Article ID 391384, 12 pages doi:10.1155/2011/391384 Research Article Mouse Model Resources for Vision Research Jungyeon Won, Lan Ying Shi, Wanda Hicks, Jieping Wang, Ronald Hurd, Jurgen¨ K. Naggert, Bo Chang, and Patsy M. Nishina The Jackson Laboratory, 600 Main Street, Bar Harbor, ME 04609, USA Correspondence should be addressed to Patsy M. Nishina, [email protected] Received 1 July 2010; Accepted 21 September 2010 Academic Editor: Radha Ayyagari Copyright © 2011 Jungyeon Won et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The need for mouse models, with their well-developed genetics and similarity to human physiology and anatomy, is clear and their central role in furthering our understanding of human disease is readily apparent in the literature. Mice carrying mutations that alter developmental pathways or cellular function provide model systems for analyzing defects in comparable human disorders and for testing therapeutic strategies. Mutant mice also provide reproducible, experimental systems for elucidating pathways of normal development and function. Two programs, the Eye Mutant Resource and the Translational Vision Research Models, focused on providing such models to the vision research community are described herein. Over 100 mutant lines from the Eye Mutant Resource and 60 mutant lines from the Translational Vision Research Models have been developed. The ocular diseases of the mutant lines include a wide range of phenotypes, including cataracts, retinal dysplasia and degeneration, and abnormal blood vessel formation.
[Show full text]
Brain Region-Specific Gene Signatures Revealed by Distinct Astrocyte Subpopulations Unveil Links to Glioma and Neurodegenerative
New Research Disorders of the Nervous System Brain Region-Specific Gene Signatures Revealed by Distinct Astrocyte Subpopulations Unveil Links to Glioma and Neurodegenerative Diseases Raquel Cuevas-Diaz Duran,1,2,3 Chih-Yen Wang,4 Hui Zheng,5,6,7 Benjamin Deneen,8,9,10,11 and Jia Qian Wu1,2 https://doi.org/10.1523/ENEURO.0288-18.2019 1The Vivian L. Smith Department of Neurosurgery, McGovern Medical School, University of Texas Health Science Center at Houston, Houston, Texas 77030, 2Center for Stem Cell and Regenerative Medicine, UT Brown Foundation Institute of Molecular Medicine, Houston, Texas 77030, 3Tecnologico de Monterrey, Escuela de Medicina y Ciencias de la Salud, Monterrey NL 64710, Mexico, 4Department of Life Sciences, National Cheng Kung University, Tainan City 70101, Taiwan, 5Huffington Center on Aging, 6Medical Scientist Training Program, 7Department of Molecular and Human Genetics, 8Center for Cell and Gene Therapy, 9Department of Neuroscience, 10Neurological Research Institute at Texas’ Children’s Hospital, and 11Program in Developmental Biology, Baylor College of Medicine, Houston, Texas 77030 Abstract Currently, there are no effective treatments for glioma or for neurodegenerative diseases because of, in part, our limited understanding of the pathophysiology and cellular heterogeneity of these diseases. Mounting evidence suggests that astrocytes play an active role in the pathogenesis of these diseases by contributing to a diverse range of pathophysiological states. In a previous study, five molecularly distinct astrocyte subpopulations from three different brain regions were identified. To further delineate the underlying diversity of these populations, we obtained mouse brain region-specific gene signatures for both protein-coding and long non-coding RNA and found that these astrocyte subpopulations are endowed with unique molecular signatures across diverse brain regions.
[Show full text]
Genetic Analyses of Human Fetal Retinal Pigment Epithelium Gene Expression Suggest Ocular Disease Mechanisms
ARTICLE https://doi.org/10.1038/s42003-019-0430-6 OPEN Genetic analyses of human fetal retinal pigment epithelium gene expression suggest ocular disease mechanisms Boxiang Liu 1,6, Melissa A. Calton2,6, Nathan S. Abell2, Gillie Benchorin2, Michael J. Gloudemans 3, 1234567890():,; Ming Chen2, Jane Hu4, Xin Li 5, Brunilda Balliu5, Dean Bok4, Stephen B. Montgomery 2,5 & Douglas Vollrath2 The retinal pigment epithelium (RPE) serves vital roles in ocular development and retinal homeostasis but has limited representation in large-scale functional genomics datasets. Understanding how common human genetic variants affect RPE gene expression could elu- cidate the sources of phenotypic variability in selected monogenic ocular diseases and pin- point causal genes at genome-wide association study (GWAS) loci. We interrogated the genetics of gene expression of cultured human fetal RPE (fRPE) cells under two metabolic conditions and discovered hundreds of shared or condition-speciﬁc expression or splice quantitative trait loci (e/sQTLs). Co-localizations of fRPE e/sQTLs with age-related macular degeneration (AMD) and myopia GWAS data suggest new candidate genes, and mechan- isms by which a common RDH5 allele contributes to both increased AMD risk and decreased myopia risk. Our study highlights the unique transcriptomic characteristics of fRPE and provides a resource to connect e/sQTLs in a critical ocular cell type to monogenic and complex eye disorders. 1 Department of Biology, Stanford University, Stanford, CA 94305, USA. 2 Department of Genetics, Stanford University School of Medicine, Stanford, CA 94305, USA. 3 Program in Biomedical Informatics, Stanford University School of Medicine, Stanford 94305 CA, USA. 4 Department of Ophthalmology, Jules Stein Eye Institute, UCLA, Los Angeles 90095 CA, USA.
[Show full text]
WO 2016/094874 Al O
(12) INTERNATIONAL APPLICATION PUBLISHED UNDER THE PATENT COOPERATION TREATY (PCT) (19) World Intellectual Property Organization International Bureau (10) International Publication Number (43) International Publication Date WO 2016/094874 Al 16 June 2016 (16.06.2016) W P O P C T (51) International Patent Classification: (74) Agents: KOWALSKI, Thomas J. et al; Vedder Price C12N 15/11 (2006.01) P.C., 1633 Broadway, New York, NY 1001 9 (US). (21) International Application Number: (81) Designated States (unless otherwise indicated, for every PCT/US2015/065396 kind of national protection available): AE, AG, AL, AM, AO, AT, AU, AZ, BA, BB, BG, BH, BN, BR, BW, BY, (22) International Filing Date: BZ, CA, CH, CL, CN, CO, CR, CU, CZ, DE, DK, DM, 11 December 2015 ( 11.12.2015) DO, DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, (25) Filing Language: English HN, HR, HU, ID, IL, IN, IR, IS, JP, KE, KG, KN, KP, KR, KZ, LA, LC, LK, LR, LS, LU, LY, MA, MD, ME, MG, (26) Publication Language: English MK, MN, MW, MX, MY, MZ, NA, NG, NI, NO, NZ, OM, (30) Priority Data: PA, PE, PG, PH, PL, PT, QA, RO, RS, RU, RW, SA, SC, 62/091,456 12 December 2014 (12. 12.2014) US SD, SE, SG, SK, SL, SM, ST, SV, SY, TH, TJ, TM, TN, 62/180,692 17 June 2015 (17.06.2015) US TR, TT, TZ, UA, UG, US, UZ, VC, VN, ZA, ZM, ZW. (71) Applicants: THE BROAD INSTITUTE INC. [US/US]; (84) Designated States (unless otherwise indicated, for every 415 Main Street, Cambridge, MA 02142 (US).
[Show full text]
Introduction
Introduction Nanophthalmos is a rare congenital ocular disorder, included in the spectrum of developmental eye diseases, characterized by a small eye, due to a compromised eye growth after the closure of the embryonic fissure1. Nanophthalmos is derived from the Greek word nano, meaning dwarf, and nanophthalmic eyes typically exhibit very high to extreme axial hyperopia and lack overt structural defects2,3. Several modes of inheritance have been described in the literature, namely autosomal dominant and recessive3,4,5. Data derived from linkage studies and the identification of genetic mutations, as the cause of non-syndromic and syndromic nanophthalmos, have been of great value towards the clarification of the pathophysiology behind these conditions6. Two loci for autosomal dominant nanophthalmos (NNO1 and NNO3) have been identified4,6. The NNO1 locus maps to chromosome 11p while the NNO3 locus (OMIM #611897) maps to chromosome 2q11-q14. Autosomal recessive nanophthalmos (NNO2) (OMIM #609549) can be caused by mutations in the MFRP gene (OMIM #606227) on chromosome 11q235. Sundin et al. (2005) performed linkage analysis using DNA samples from 16 members of the Amish-Mennonite kindred originally reported by Cross and Yoder (1976), including 5 individuals with nanophthalmos3,5. Mutations in the membrane- type frizzled related protein (MFRP) gene were identified as the cause of classic non- syndromic Mendelian recessive nanophthalmos5. MFRP has 13 exons, which translate into 579 aminoacids. The resulting protein consists of three domains: a transmembrane domain with homology to the frizzled 1 family of proteins, containing two cubilin domains; a low density lipoprotein receptor a; and a cysteine-rich domain, that can bind with wingless type proteins (WNTs), which might be involved in eye development, through mediating cell growth7.
[Show full text]
Dominant Variants in the Splicing Factor PUF60 Cause a Recognizable Syndrome with Intellectual Disability, Heart Defects and Short Stature
European Journal of Human Genetics (2017) 25, 43–51 & 2017 Macmillan Publishers Limited, part of Springer Nature. All rights reserved 1018-4813/17 www.nature.com/ejhg ARTICLE Dominant variants in the splicing factor PUF60 cause a recognizable syndrome with intellectual disability, heart defects and short stature Salima El Chehadeh*,1,2, Wilhelmina S Kerstjens-Frederikse3, Julien Thevenon1,4, Paul Kuentz1,4,5, Ange-Line Bruel4, Christel Thauvin-Robinet1,4, Candace Bensignor6, Hélène Dollfus2,7, Vincent Laugel7,8, Jean-Baptiste Rivière1,4,5, Yannis Duffourd1, Caroline Bonnet9, Matthieu P Robert10,11, Rodica Isaiko12, Morgane Straub12, Catherine Creuzot-Garcher12, Patrick Calvas13, Nicolas Chassaing13, Bart Loeys14, Edwin Reyniers14, Geert Vandeweyer14, Frank Kooy14, Miroslava Hančárová15, Marketa Havlovicová15, Darina Prchalová15, Zdenek Sedláček15, Christian Gilissen16, Rolph Pfundt16, Jolien S Klein Wassink-Ruiter3 and Laurence Faivre1,4 Verheij syndrome, also called 8q24.3 microdeletion syndrome, is a rare condition characterized by ante- and postnatal growth retardation, microcephaly, vertebral anomalies, joint laxity/dislocation, developmental delay (DD), cardiac and renal defects and dysmorphic features. Recently, PUF60 (Poly-U Binding Splicing Factor 60 kDa), which encodes a component of the spliceosome, has been discussed as the best candidate gene for the Verheij syndrome phenotype, regarding the cardiac and short stature phenotype. To date, only one patient has been reported with a de novo variant in PUF60 that probably affects function (c.505C4T leading to p.(His169Tyr)) associated with DD, microcephaly, craniofacial and cardiac defects. Additional patients were required to confirm the pathogenesis of this association and further delineate the clinical spectrum. Here we report five patients with de novo heterozygous variants in PUF60 identified using whole exome sequencing.
[Show full text]