An ARL3–UNC119–RP2 Gtpase Cycle Targets Myristoylated NPHP3 to the Primary Cilium
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Retinal Dystrophy Panel Plus
ANALYSIS REPORT Patient: Test, Test 1; DoB: 1989-Apr-10; Order ID: 54324 SUMMARY DIAGNOSTIC FINDING Retinal Dystrophy Panel Plus PATIENT INFORMATION NAME DOB SSN AGE GENDER ORDER ID Test, test1 1989-Apr-10 10041989-xxxx 28 Male 54324 REFERRING HEALTHCARE PROFESSIONAL NAME HOSPITAL Anna Smith Test hospital SUMMARY OF CLINICAL HISTORY Patient is a 28-year-old male with VA 20/40 OD, 20/50 OS, constricted visual fields, non-detectable rod ffERG, and a family history consistent with X-linked retinitis pigmentosa. SEQUENCE ANALYSIS RESULTS GENE NOMENCLATURE INHERITANCE ZYGOSITY CLASSIFICATION RPGR c.2655_2656del, p.(Glu886Glyfs*192) X-linked HEM LIKELY PATHOGENIC DEL/DUP (CNV) ANALYSIS RESULTS Del/Dup (CNV) analysis did not detect any known disease-causing copy number variation or novel or rare deletion/duplication that was considered deleterious. CONCLUSION We classify the identifiedRPGR c.2655_2656del, p.(Glu886Glyfs*192) as likely pathogenic and the probable cause for the patient’s disease, considering the current evidence of the variant (established association between the gene and the patient’s phenotype, rarity in control populations, identification of the variant in an individual with the same phenotype, and mutation type: frameshift). However, additional information is still needed to confirm the pathogenicity of the variant, which could allow independent risk stratification based on this mutation. Genetic counseling and family member testing is recommended. Disease caused by RPGR mutations is inherited in an X-linked manner. We recommend carrier testing of the mother. If the mother is a carrier, then each offspring has a 50% chance of inheriting the mutation. Disease caused byRPGR mutations is inherited in an X-linked manner, and thus each daughter of an affected male will inherit the mutation, while sons will remain unaffected. -
GENETIC STUDY of RENAL DISEASES (Nephroref Global®) by MASSIVE SEQUENCING (NGS)
Pablo Iglesias, 57 – Polígono Gran Via Sur 08908 L'Hospitalet de Llobregat (Barcelona) Tel. 932 593 700 – Fax. 932 845 000 GENETIC STUDY OF RENAL DISEASES (NephroRef Global®) BY MASSIVE SEQUENCING (NGS) Request No.: 000 Client: - Analysis code: 55580 Patient Name: xxx Date of Birth: N/A Patient Ref.: xxx Gender: Female Sample Type: Blood EDTA Sample Arrival Date: DD/MM/AAAA Date of Result: DD/MM/AAAA Clinical information: A 9-year-old patient with a nephrotic syndrome without response to corticosteroid therapy. She has nephrotic-range proteinuria with microhematuria, hypoalbuminemia with hypercholesterolemia and normal glomerular filtration. Paternal aunt with cortico-resistant nephrotic syndrome with evolution to end-stage renal failure that required renal transplantation at age 13. RESULT AND INTERPRETATION The presence of a heterozygous likely pathogenic variant has been identified. In addition, the presence of a heterozygous variant of uncertain clinical significance (VUS) has been identified.(See Interpretation and recommendations) The complete list of studied genes is available in Annex 1. (Methodology) The list of reported genes and coverage details is available in Table 1. (Methodology) Gene Variant* Zygosity Inheritance pattern Classification^ NPHS2 NM_014625.3: c.842A>C Heterozygosis Autosomal Recessive Likely Patogénica p.(Glu281Ala) INF2 NM_022489.3: c.67T>A Heterozygosis Autosomal Recessive VUS p.(Ser23Thr) * Nomenclature according to HGVS v15.11 ^ Based on the recommendations of the American College of Medical Genetics and Genomics (ACMG) Physician, technical specialist responsible for Clinical Analysis: Jaime Torrents Pont. The results relate to samples received and analysed. This report may not be reproduced in part without permission. This document is addressed to the addressee and contains confidential information. -
Building the Vertebrate Codex Using the Gene Breaking Protein Trap Library
Genetics, Development and Cell Biology Publications Genetics, Development and Cell Biology 2020 Building the vertebrate codex using the gene breaking protein trap library Noriko Ichino Mayo Clinic Gaurav K. Varshney National Institutes of Health Ying Wang Iowa State University Hsin-kai Liao Iowa State University Maura McGrail Iowa State University, [email protected] See next page for additional authors Follow this and additional works at: https://lib.dr.iastate.edu/gdcb_las_pubs Part of the Molecular Genetics Commons, and the Research Methods in Life Sciences Commons The complete bibliographic information for this item can be found at https://lib.dr.iastate.edu/ gdcb_las_pubs/261. For information on how to cite this item, please visit http://lib.dr.iastate.edu/howtocite.html. This Article is brought to you for free and open access by the Genetics, Development and Cell Biology at Iowa State University Digital Repository. It has been accepted for inclusion in Genetics, Development and Cell Biology Publications by an authorized administrator of Iowa State University Digital Repository. For more information, please contact [email protected]. Building the vertebrate codex using the gene breaking protein trap library Abstract One key bottleneck in understanding the human genome is the relative under-characterization of 90% of protein coding regions. We report a collection of 1200 transgenic zebrafish strains made with the gene- break transposon (GBT) protein trap to simultaneously report and reversibly knockdown the tagged genes. Protein trap-associated mRFP expression shows previously undocumented expression of 35% and 90% of cloned genes at 2 and 4 days post-fertilization, respectively. Further, investigated alleles regularly show 99% gene-specific mRNA knockdown. -
RP2 Antibody / XRP2 (RQ4671)
RP2 Antibody / XRP2 (RQ4671) Catalog No. Formulation Size RQ4671 0.5mg/ml if reconstituted with 0.2ml sterile DI water 100 ug Bulk quote request Availability 1-3 business days Species Reactivity Human, Mouse, Rat Format Antigen affinity purified Clonality Polyclonal (rabbit origin) Isotype Rabbit IgG Purity Antigen affinity purified Buffer Lyophilized from 1X PBS with 2% Trehalose and 0.025% sodium azide UniProt O75695 Applications Western blot : 0.5-1ug/ml Immunohistochemistry (FFPE) : 1-2ug/ml Immunofluorescence : 2-4ug/ml Flow cytometry : 1-3ug/million cells Direct ELISA : 0.1-0.5ug/ml (human recombinant protein) Limitations This RP2 antibody is available for research use only. Western blot testing of 1) human placenta, 2) human SGC-7901, 3) rat lung and 4) mouse lung lysate with RP2 antibody at 0.5ug/ml. Predicted molecular weight ~40 kDa. IHC staining of FFPE human placenta with RP2 antibody at 1ug/ml. HIER: boil tissue sections in pH6, 10mM citrate buffer, for 10-20 min followed by cooling at RT for 20 min. IHC staining of FFPE human placenta with RP2 antibody at 1ug/ml. HIER: boil tissue sections in pH6, 10mM citrate buffer, for 10-20 min followed by cooling at RT for 20 min. IHC staining of FFPE human lung cancer with RP2 antibody at 1ug/ml. HIER: boil tissue sections in pH6, 10mM citrate buffer, for 10-20 min followed by cooling at RT for 20 min. IHC staining of FFPE human breast cancer with RP2 antibody at 1ug/ml. HIER: boil tissue sections in pH6, 10mM citrate buffer, for 10-20 min followed by cooling at RT for 20 min. -
Pigmentosa in a Large Kindred
J Med Genet: first published as 10.1136/jmg.28.7.453 on 1 July 1991. Downloaded from I Med Genet 1991; 28: 453-457 453 Genetic localisation of the RP2 type of X linked retinitis pigmentosa in a large kindred A F Wright, SS Bhattacharya, M A Aldred, M Jay, A D Carothers, N S T Thomas, A C Bird, B Jay, H J Evans Abstract and usually loss of central vision before the fourth Genetic linkage and deletion studies have led to the decade. At least 14 to 15% of families and 15 to 28% of proposal that there are at least two loci on the X retinitis pigmentosa patients in the UK have the X chromosome which are responsible for X linked linked disorder' 2 so that the population prevalence is retinitis pigmentosa (XLRP). One locus (RP3) has in the region of 1 in 10 000 to 30 000. been closely defined by genetic linkage and deletion XLRP was first mapped to the proximal short arm analyses and localised to the region between the of the X chromosome by genetic linkage to DXS7, ornithine transcarbamylase (OTC) and chronic localised to Xpl l.-pll .3.3 Subsequent linkage granulomatous disease (CYBB) loci in Xp2l.1- studies have supported locations both proximal49 and pII.4. The other locus (RP2) has been assigned by distal'o'3 to the DXS7 locus. The situation was linkage analysis alone to region Xpll.4-pll.2, but clarified by a heterogeneity analysis of 62 XLRP its localisation is less weli defined. The results of a kindreds from nine centres, in which it was shown multipoint linkage analysis of a single large XLRP that the overall likelihood was 6-4x 109:1 in favour of kindred using eight informative loci provide further two loci versus a single XLRP locus. -
Evidence of Oligogenic Inheritance in Nephronophthisis
JASN Express. Published on September 12, 2007 as doi: 10.1681/ASN.2007020243 CLINICAL RESEARCH www.jasn.org Evidence of Oligogenic Inheritance in Nephronophthisis Julia Hoefele,*† Matthias T.F. Wolf,* John F. O’Toole,* Edgar A. Otto,* Ulla Schultheiss,* Georges Deˆschenes,‡ Massimo Attanasio,* Boris Utsch,* Corinne Antignac,§ and ʈ Friedhelm Hildebrandt* ʈ Departments of *Pediatrics and Human Genetics, University of Michigan, Ann Arbor, Michigan; †Department of Pediatrics, University Children’s Hospital, University of Munich, Munich, Germany; and ‡Hoˆpital Robert Debre´, Pediatric Nephrology, AP-HP, and §INSERM, U574, Universite´ Paris Descartes, Faculte de Me´dicine Rene´ Descartes, and Hoˆpital Necker-Enfants Malades, AP-HP, Department of Genetics, Paris, France ABSTRACT Nephronophthisis is a recessive cystic renal disease that leads to end-stage renal failure in the first two decades of life. Twenty-five percent of nephronophthisis cases are caused by large homozygous deletions of NPHP1, but six genes responsible for nephronophthisis have been identified. Because oligogenic inheritance has been described for the related Bardet-Biedl syndrome, we evaluated whether mutations in more than one gene may also be detected in cases of nephronophthisis. Because the nephrocystins 1 to 4 are known to interact, we examined patients with nephronophthisis from 94 different families and sequenced all exons of the NPHP1, NPHP2, NPHP3, and NPHP4 genes. In our previous studies involving 44 families, we detected two mutations in one of the NPHP1–4 genes. Here, we detected in six families two mutations in either NPHP1, NPHP3, or NPHP4, and identified a third mutation in one of the other NPHP genes. Furthermore, we found possible digenic disease by detecting one individual who carried one mutation in NPHP2 and a second mutation in NPHP3. -
Renal Cystic Disorders Infosheet 6-14-19
Next Generation Sequencing Panel for Renal Cystic Disorders Clinical Features: Renal cystic diseases are a genetically heterogeneous group of conditions characterized By isolated renal disease or renal cysts in conjunction with extrarenal features (1). Age of onset of renal cystic disease ranges from neonatal to adult onset. Common features of renal cystic diseases include renal insufficiency and progression to end stage renal disease (ESRD). Identification of the genetic etiology of renal cystic disease can aid in appropriate clinical management of the affected patient. Our Renal Cystic Disorders Panel includes sequence and deletion/duplicaton analysis of all 79 genes listed below. Renal Cystic Disorders Sequencing Panel AHI1 BMPER HNF1B NEK8 TCTN3 WDPCP ANKS6 C5orf42 IFT27 NOTCH2 TFAP2A WDR19 ARL13B CC2D2A IFT140 NPHP1 TMEM107 XPNPEP3 ARL6 CDC73 IFT172 NPHP3 TMEM138 ZNF423 B9D1 CEP104 INPP5E NPHP4 TMEM216 B9D2 CEP120 INVS OFD1 TMEM231 BBIP1 CEP164 IQCB1 PDE6D TMEM237 BBS1 CEP290 JAG1 PKD2 TMEM67 BBS10 CEP41 KIAA0556 PKHD1 TRIM32 BBS12 CEP83 KIAA0586 REN TSC1 BBS2 CRB2 KIF14 RPGRIP1L TSC2 BBS4 CSPP1 KIF7 SALL1 TTC21B BBS5 DCDC2 LZTFL1 SDCCAG8 TTC8 BBS7 GLIS2 MKKS TCTN1 UMOD BBS9 GLIS3 MKS1 TCTN2 VHL Disorder Genes Inheritance Clinical features/molecular genetics Bardet Biedl ARL6 AR Bardet-Biedl syndrome (BBS) is an autosomal syndrome BBS1 recessive multi-systemic ciliopathy characterized By BBS10 retinal dystrophy, oBesity, postaxial polydactyly, BBS12 leaning difficulties, renal involvement and BBS2 genitourinary abnormalities (2). Visual prognosis is BBS4 poor, and the mean age of legal Blindness is 15.5 BBS5 years. Birth weight is typically normal But significant BBS7 weight gain Begins within the first year. Renal BBS9 disease is a major cause of morBidity and mortality. -
RP2 Phenotype and Pathogenetic Correlations in X-Linked Retinitis Pigmentosa
OPHTHALMIC MOLECULAR GENETICS SECTION EDITOR: JANEY L. WIGGS, MD, PhD RP2 Phenotype and Pathogenetic Correlations in X-Linked Retinitis Pigmentosa Thiran Jayasundera, MD; Kari E. H. Branham, MS; Mohammad Othman, PhD; William R. Rhoades, BS; Athanasios J. Karoukis, BS; Hemant Khanna, PhD; Anand Swaroop, PhD; John R. Heckenlively, MD Objectives: To assess the phenotype of patients with function. All 3 female carriers had macular atrophy in 1 X-linked retinitis pigmentosa (XLRP) with RP2 muta- or both eyes and were myopic (mean, −6.23 D). All 9 non- tions and to correlate the findings with their genotype. sense and frameshift and 5 of 7 missense mutations (71%) resulted in severe clinical presentations. Methods: Six hundred eleven patients with RP were screened for RP2 mutations. From this screen, 18 pa- Conclusions: Screening of the RP2 gene should be pri- tients with RP2 mutations were evaluated clinically with oritized in patients younger than 16 years characterized standardized electroretinography, Goldmann visual fields, by X-linked inheritance, decreased best-corrected vi- and ocular examinations. In addition, 7 well-docu- sual acuity (eg, Ͼ20/40), high myopia, and early-onset mented cases from the literature were used to augment macular atrophy. Patients exhibiting a choroideremia- genotype-phenotype correlations. like fundus without choroideremia gene mutations should also be screened for RP2 mutations. Results: Of 11 boys younger than 12 years, 10 (91%) had macular involvement and 9 (82%) had best- Clinical Relevance: An identifiable phenotype for corrected visual acuity worse than 20/50. Two boys from RP2-XLRP aids in clinical diagnosis and targeted genetic different families (aged 8 and 12 years) displayed a cho- roideremia-like fundus, and 9 boys (82%) were myopic screening. -
Novel Candidate Genes of Thyroid Tumourigenesis Identified in Trk-T1 Transgenic Mice
Endocrine-Related Cancer (2012) 19 409–421 Novel candidate genes of thyroid tumourigenesis identified in Trk-T1 transgenic mice Katrin-Janine Heiliger*, Julia Hess*, Donata Vitagliano1, Paolo Salerno1, Herbert Braselmann, Giuliana Salvatore 2, Clara Ugolini 3, Isolde Summerer 4, Tatjana Bogdanova5, Kristian Unger 6, Gerry Thomas6, Massimo Santoro1 and Horst Zitzelsberger Research Unit of Radiation Cytogenetics, Helmholtz Zentrum Mu¨nchen, Ingolsta¨dter Landstr. 1, 85764 Neuherberg, Germany 1Istituto di Endocrinologia ed Oncologia Sperimentale del CNR, c/o Dipartimento di Biologia e Patologia Cellulare e Molecolare, Universita` Federico II, Naples 80131, Italy 2Dipartimento di Studi delle Istituzioni e dei Sistemi Territoriali, Universita` ‘Parthenope’, Naples 80133, Italy 3Division of Pathology, Department of Surgery, University of Pisa, 56100 Pisa, Italy 4Institute of Radiation Biology, Helmholtz Zentrum Mu¨nchen, 85764 Neuherberg, Germany 5Institute of Endocrinology and Metabolism, Academy of Medical Sciences of the Ukraine, 254114 Kiev, Ukraine 6Department of Surgery and Cancer, Imperial College London, Hammersmith Hospital, London W12 0HS, UK (Correspondence should be addressed to H Zitzelsberger; Email: [email protected]) *(K-J Heiliger and J Hess contributed equally to this work) Abstract For an identification of novel candidate genes in thyroid tumourigenesis, we have investigated gene copy number changes in a Trk-T1 transgenic mouse model of thyroid neoplasia. For this aim, 30 thyroid tumours from Trk-T1 transgenics were investigated by comparative genomic hybridisation. Recurrent gene copy number alterations were identified and genes located in the altered chromosomal regions were analysed by Gene Ontology term enrichment analysis in order to reveal gene functions potentially associated with thyroid tumourigenesis. In thyroid neoplasms from Trk-T1 mice, a recurrent gain on chromosomal bands 1C4–E2.3 (10.0% of cases), and losses on 3H1–H3 (13.3%), 4D2.3–E2 (43.3%) and 14E4–E5 (6.7%) were identified. -
Development of Novel Drugs Targeting Chaperones of Oncogenic K-Ras
Farid Ahmad Siddiqui Farid Ahmad Siddiqui // Development of Novel Drugs Development of Novel Drugs Targeting Chaperones of Oncogenic K-Ras of Oncogenic Chaperones K-Ras Drugs Targeting of Novel Development Targeting Chaperones of Oncogenic K-Ras // 2021 9 789521 240317 ISBN 978-952-12-4031-7 Development of Novel Drugs Targeting Chaperones of Oncogenic K-Ras Farid Ahmad Siddiqui Cell Biology Faculty of Science and Engineering, Åbo Akademi University Turku Bioscience Centre University of Turku & Åbo Akademi University Turku, Finland, 2021 From the Turku Bioscience Centre, University of Turku and Åbo Akademi University, Faculty of Science and Engineering, Åbo Akademi University, Turku, Finland Supervised by Prof. Daniel Abankwa, PhD Department of Life Sciences and Medicine University of Luxembourg, Belval campus Luxembourg Reviewed by Prof. Olli Mikael Carpen, PhD Faculty of Medicine University of Helsinki Helsinki, Finland and Prof. Klaus Elenius, PhD Faculty of Medicine University of Turku Turku, Finland Opponent Prof. Krishnaraj Rajalingam, PhD Head, Cell Biology Unit, UMC-Mainz, Germany Author’s address Turku Bioscience Centre Åbo Akademi University Tykistökatu 6 20520 Turku Finland Email: [email protected] ISBN 978-952-12-4031-7 (printed) ISBN 978-952-12-4032-4 (digital) Painosalama Oy, Turku, Finland 2021 TABLE OF CONTENTS ABSTRACT .......................................................................................................... 6 ABSTRAKT (Swedish Abstract) ......................................................................... -
Human Induced Pluripotent Stem Cell–Derived Podocytes Mature Into Vascularized Glomeruli Upon Experimental Transplantation
BASIC RESEARCH www.jasn.org Human Induced Pluripotent Stem Cell–Derived Podocytes Mature into Vascularized Glomeruli upon Experimental Transplantation † Sazia Sharmin,* Atsuhiro Taguchi,* Yusuke Kaku,* Yasuhiro Yoshimura,* Tomoko Ohmori,* ‡ † ‡ Tetsushi Sakuma, Masashi Mukoyama, Takashi Yamamoto, Hidetake Kurihara,§ and | Ryuichi Nishinakamura* *Department of Kidney Development, Institute of Molecular Embryology and Genetics, and †Department of Nephrology, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan; ‡Department of Mathematical and Life Sciences, Graduate School of Science, Hiroshima University, Hiroshima, Japan; §Division of Anatomy, Juntendo University School of Medicine, Tokyo, Japan; and |Japan Science and Technology Agency, CREST, Kumamoto, Japan ABSTRACT Glomerular podocytes express proteins, such as nephrin, that constitute the slit diaphragm, thereby contributing to the filtration process in the kidney. Glomerular development has been analyzed mainly in mice, whereas analysis of human kidney development has been minimal because of limited access to embryonic kidneys. We previously reported the induction of three-dimensional primordial glomeruli from human induced pluripotent stem (iPS) cells. Here, using transcription activator–like effector nuclease-mediated homologous recombination, we generated human iPS cell lines that express green fluorescent protein (GFP) in the NPHS1 locus, which encodes nephrin, and we show that GFP expression facilitated accurate visualization of nephrin-positive podocyte formation in -
Analysis of RP2 and RPGR Mutations in Five X-Linked Chinese Families
www.nature.com/scientificreports OPEN Analysis of RP2 and RPGR Mutations in Five X-Linked Chinese Families with Retinitis Pigmentosa Received: 07 December 2016 Jingjing Jiang1,*, Xiaofei Wu2,*, Di Shen3,*, Lijin Dong4, Xiaodong Jiao5, J. Fielding Hejtmancik5 Accepted: 08 February 2017 & Ningdong Li1,2,5 Published: 15 March 2017 Mutations in RP2 and RPGR genes are responsible for the X-linked retinitis pigmentosa (XLRP). In this study, we analyzed the RP2 and RPGR gene mutations in five Han Chinese families with XLRP. An approximately 17Kb large deletion including the exon 4 and exon 5 of RP2 gene was found in an XLRP family. In addition, four frameshift mutations including three novel mutations of c.1059 + 1 G > T, c.2002dupC and c.2236_2237del CT, as well as a previously reported mutation of c.2899delG were detected in the RPGR gene in the other four families. Our study further expands the mutation spectrum of RP2 and RPGR, and will be helpful for further study molecular pathogenesis of XLRP. Retinitis pigmentosa (RP) is a clinically and genetically heterogeneous group of retinal dystrophies characterized by photoreceptor cell degeneration. The prevalence of RP is about 1/4000 ~1/5000 according to studies in dif- ferent populations1. The clinical features comprise night blindness, progressive constriction of visual field with age, and fundus changes including attenuation of the retinal arterioles, bone spicule-like pigment deposits in the mid-peripheral retinal and waxy pallor of the optic disc. Affected individuals often have severely abnormal or non-detectable rod responses in the electroretinograms (ERG) recordings even in the early stage of the disease2.