DOCSLIB.ORG

A Homozygous STIM1 Mutation Impairs Store-Operated Calcium

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
A Homozygous STIM1 Mutation Impairs Store-Operated Calcium J ALLERGY CLIN IMMUNOL LETTERS TO THE EDITOR 955 VOLUME 137, NUMBER 3 Kejian Zhang, MDb recessive AI and hypohidrosis by using autozygosity mapping Stella Davies, MBBS, PhD, MRCPa and clonal sequencing. A homozygous rare missense mutation a Alexandra H. Filipovich, MD in STIM1 (p.L74P) in the EF-hand domain was identified (see From the Divisions of aBone Marrow Transplantation and Immune deficiency and the Methods and Results sections in this article’s Online Reposi- bHuman Genetics, Cincinnati Children’s Hospital Medical Center, Cincinnati, tory at www.jacionline.org). Ohio. E-mail: [email protected]. The family was re-evaluated, with particular attention paid to Disclosure of potential conflict of interest: The authors declare that they have no relevant conflicts of interest. features associated with recessive STIM1 mutations (Table I and see Tables E1-E3 in this article’s Online Repository at www.jacionline. org). The 2 affected cousins (18 and 11 years old, respectively) did REFERENCES 1. Bennett CL, Christie J, Ramsdell F, Brunkow ME, Ferguson PJ, Whitesell L, et al. not have overt clinical immunodeficiency. Further evaluation of The immune dysregulation, polyendocrinopathy, enteropathy, X-linked syndrome their immune systems showed a normal immunoglobulin profile (IPEX) is caused by mutations of FOXP3. Nat Genet 2001;27:20-1. with an adequate specific antibody response to both nonlive (pneu- 2. Barzaghi F, Passerini L, Bacchetta R. Immune dysregulation, polyendocrinopathy, mococcus, tetanus and, Hib) and live (mumps, measles, and enteropathy, x-linked syndrome: a paradigm of immunodeficiency with autoimmu- nity. Front Immunol 2012;3:211. rubella) vaccinations. In addition, both subjects had detectable 3. Baud O, Goulet O, Canioni D, Le Deist F, Radford I, Rieu D, et al. Treatment of the IgG against varicella zoster virus after a previous uncomplicated immune dysregulation, polyendocrinopathy, enteropathy, X-linked syndrome primary infection. The younger cousin was also found to have (IPEX) by allogeneic bone marrow transplantation. N Engl J Med 2001;344:1758-62. IgG against EBV viral capsid antigen, suggesting previous expo- 4. Rao A, Kamani N, Filipovich A, Lee SM, Davies SM, Dalal J, et al. Successful sure, but neither showed any evidence of acute infection or previous bone marrow transplantation for IPEX syndrome after reduced-intensity condition- ing. Blood 2007;109:383-5. exposure to cytomegalovirus. 5. Burroughs LM, Torgerson TR, Storb R, Carpenter PA, Rawlings DJ, Sanders J, Lymphocyte studies showed stable CD8 T-cell depletion in the et al. Stable hematopoietic cell engraftment after low-intensity nonmyeloablative older affected subject only. Other lymphocyte subsets, including conditioning in patients with immune dysregulation, polyendocrinopathy, enterop- CD4 T, natural killer (NK), and B cells, were within the normal athy, X-linked syndrome. J Allergy Clin Immunol 2010;126:1000-5. 6. Nademi Z, Slatter M, Gambineri E, Mannurita SC, Barge D, Hodges S, et al. Sin- range (Table I). However, despite normal PHA and anti-CD3 gle centre experience of haematopoietic SCT for patients with immunodysregula- simulation responses, T-lymphocyte and NK cell SOCE was tion, polyendocrinopathy, enteropathy, X-linked syndrome. Bone Marrow grossly abnormal, which is consistent with disruption of the Transplant 2014;49:310-2. Ca21-binding EF-hand and in keeping with previous reports for 7. Wildin RS, Smyk-Pearson S, Filipovich AH. Clinical and molecular features of the recessive STIM1 mutations (see Fig E1, A, in this article’s Online immunodysregulation, polyendocrinopathy, enteropathy, X linked (IPEX) syn- 1-3 drome. J Med Genet 2002;39:537-45. Repository at www.jacionline.org). The defect in NK cell 8. Marsh RA, Vaughn G, Kim MO, Li D, Jodele S, Joshi S, et al. Reduced-intensity SOCE was associated with impaired NK cell effector function, conditioning significantly improves survival of patients with hemophagocytic lym- as shown by assays of granule exocytosis and intracellular phohistiocytosis undergoing allogeneic hematopoietic cell transplantation. Blood IFN-g production in response to K562 tumor cells (see Fig E1, 2010;116:5824-31. 9. Burroughs LM, Nemecek ER, Torgerson TR, Storer BE, Talano JA, Domm J, et al. B). After recently published mouse studies, which confirmed Treosulfan-based conditioning and hematopoietic cell transplantation for nonma- the importance of STIM1 to neutrophil SOCE and associated lignant diseases: a prospective multicenter trial. Biol Blood Marrow Transplant functions,4 we also evaluated neutrophil function. This was found 2014;20:1996-2003. to be within normal limits. Despite abnormal immune system SOCE, the affected subjects Available online November 11, 2015. http://dx.doi.org/10.1016/j.jaci.2015.09.030 in this case appear to be able to compensate for this deficit and avoid overt immunodeficiency. It is possible that the relative preservation of T-cell function might compensate for NK cell A homozygous STIM1 mutation dysfunction. Neither might yet have encountered a pathogen impairs store-operated calcium that would expose this particular immune system limitation (see entry and natural killer cell Table E2). An ability to mount a partial response to viral effector function without clinical infections was reported in a family with clinical immunodefi- immunodeficiency ciency and a history of viral infections caused by a homozygous missense R429C change affecting the STIM1 cytoplasmic To the Editor: domain.2 A mouse model characterized by conditional knockout Stromal interaction molecule 1 (STIM1) is a transmembrane of Stim1 and Stim2 in both CD41 and CD81 T cells has recently protein pivotal to store-operated calcium entry (SOCE) that provided further insight into the importance of Stim1 in immune localizes to either the cell or endoplasmic reticulum (ER) system development and virus-specific memory and recall membranes, with the N-terminus in either the extracellular space responses, which prevent acute viral infections from becoming or the ER, respectively. Plasma membrane ORAI calcium 5 21 chronic. release–activated calcium modulator 1 (ORAI1) Ca channels Recessive STIM1 mutations can be associated with other are activated by STIM1. Families previously described with immune dysregulations, including autoimmune disease. The recessive STIM1 mutations (MIM #612783) had life-threatening older cousin had a transient episode of idiopathic thrombocyto- viral, bacterial, and fungal infections; developmental myopathy; penic purpura when 2 years old that might have been unrelated hypohidrosis; and amelogenesis imperfecta (AI; generalized 1-3 to the STIM1 mutations. There were no other clinical or serologic developmental enamel abnormalities). We investigated a markers consistent with autoimmune disease, and regulatory consanguineous family, segregating a novel syndrome of T-cell numbers were normal. Ó 2015 The Authors. Published by Elsevier Inc. on behalf of the American Academy of Both cousins were intolerant of warm environments and aware Allergy, Asthma & Immunology. This is an open access article under the CC BY license of their inability to sweat normally. This limited the older cousin’s (http://creativecommons.org/licenses/by/4.0/). ability to participate in sport. There was no clinical or serologic 956 LETTERS TO THE EDITOR J ALLERGY CLIN IMMUNOL MARCH 2016 TABLE I. Summary of the main clinical and clinical immunologic features in subjects with either homozygous or heterozygous STIM1 c.221T>C mutations Feature V:3 IV:4 IV:3 V:2 STIM1 genotype Homozygous c.221T>C Heterozygous c.221T>C Heterozygous c.221T>C Homozygous c.221T>C Age at evaluation (y) 18-21 45-48 41 9-12 Persistent infections None None None None Other infections Infancy: repeated chest No reported issues No reported issues Infancy: chest, urinary infections but not thereafter tract, gastrointestinal tract, ear, and eye infections but not thereafter Autoimmune disorder Transient ITP aged 2.5 y None Sjogren syndrome None Lymphocytes Total (3109/L [1.00-2.80]) 1.50 2.30 2.64 2.34 CD4 (absolute; 3 109/L 0.841 1.091 1.502 0.908 [0.300-1.400]) CD8 (absolute; 3 109/L 0.055 0.236 0.415 0.488 [0.200-0.900]) CD4/CD8 (1.07-1.87) 15.29 4.62 3.62 1.86 NK (absolute; 3 109/L 0.238 0.581 0.252 0.252 [0.090-0.600]) Immunization history Full schedule without adverse Not assessed Not assessed Full schedule without events adverse events Musculoskeletal Muscle bulk, tone, power, and No issues evident; not No issues evident; Muscle bulk, tone, power, reflexes normal; hypermobility formally examined not formally examined and reflexes normal; in upper and lower limbs; hypermobility in upper CK normal and lower limbs; CK normal Pupil reaction Normal Normal Normal Normal Sweating Diminished sweating recognized No reported issues No reported issues Diminished sweating from infancy onward; insufficient recognized from infancy sample for sweat test analysis onward; reduced sweating on starch and iodine testing Dental enamel Generalized hypomineralized AI Enamel within normal Enamel within normal Generalized hypomineralized AI limits limits Development Global development normal Not assessed Not assessed Global development normal Height, 156 cm (<0.4th percentile) Height, 122 cm (0.4th-2nd Weight, 40.3 kg (<0.4th percentile) percentile) Head circumference, 51.5 cm Weight 24 kg (2nd-9th (<0.4th percentile) percentile) Head circumference, 50 cm (0.4th percentile) Further details are presented in Tables E1-E3. Values in boldface are outside the reference ranges. CK, Creatine
Load more

Recommended publications
  • Oral Health in Prevalent Types of Ehlers–Danlos Syndromes
    View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by Ghent University Academic Bibliography J Oral Pathol Med (2005) 34: 298–307 ª Blackwell Munksgaard 2005 Æ All rights reserved www.blackwellmunksgaard.com/jopm Oral health in prevalent types of Ehlers–Danlos syndromes Peter J. De Coster1, Luc C. Martens1, Anne De Paepe2 1Department of Paediatric Dentistry, Centre for Special Care, Paecamed Research, Ghent University, Ghent; 2Centre for Medical Genetics, Ghent University Hospital, Ghent, Belgium BACKGROUND: The Ehlers–Danlos syndromes (EDS) Introduction comprise a heterogenous group of heritable disorders of connective tissue, characterized by joint hypermobility, The Ehlers–Danlos syndromes (EDS) comprise a het- skin hyperextensibility and tissue fragility. Most EDS erogenous group of heritable disorders of connective types are caused by mutations in genes encoding different tissue, largely characterized by joint hypermobility, skin types of collagen or enzymes, essential for normal pro- hyperextensibility and tissue fragility (1) (Fig. 1). The cessing of collagen. clinical features, modes of inheritance and molecular METHODS: Oral health was assessed in 31 subjects with bases differ according to the type. EDS are caused by a EDS (16 with hypermobility EDS, nine with classical EDS genetic defect causing an error in the synthesis or and six with vascular EDS), including signs and symptoms processing of collagen types I, III or V. The distribution of temporomandibular disorders (TMD), alterations of and function of these collagen types are displayed in dental hard tissues, oral mucosa and periodontium, and Table 1. At present, two classifications of EDS are was compared with matched controls.
    [Show full text]
  • Spectrum of PEX1 and PEX6 Variants in Heimler Syndrome
    European Journal of Human Genetics (2016) 24, 1565–1571 Official Journal of The European Society of Human Genetics www.nature.com/ejhg ARTICLE Spectrum of PEX1 and PEX6 variants in Heimler syndrome Claire EL Smith1, James A Poulter1, Alex V Levin2,3,4, Jenina E Capasso4, Susan Price5, Tamar Ben-Yosef6, Reuven Sharony7, William G Newman8,9, Roger C Shore10, Steven J Brookes10, Alan J Mighell1,11,12 and Chris F Inglehearn*,1,12 Heimler syndrome (HS) consists of recessively inherited sensorineural hearing loss, amelogenesis imperfecta (AI) and nail abnormalities, with or without visual defects. Recently HS was shown to result from hypomorphic mutations in PEX1 or PEX6,both previously implicated in Zellweger Syndrome Spectrum Disorders (ZSSD). ZSSD are a group of conditions consisting of craniofacial and neurological abnormalities, sensory defects and multi-organ dysfunction. The finding of HS-causing mutations in PEX1 and PEX6 shows that HS represents the mild end of the ZSSD spectrum, though these conditions were previously thought to be distinct nosological entities. Here, we present six further HS families, five with PEX6 variants and one with PEX1 variants, and show the patterns of Pex1, Pex14 and Pex6 immunoreactivity in the mouse retina. While Ratbi et al. found more HS-causing mutations in PEX1 than in PEX6, as is the case for ZSSD, in this cohort PEX6 variants predominate, suggesting both genes play a significant role in HS. The PEX6 variant c.1802G4A, p.(R601Q), reported previously in compound heterozygous state in one HS and three ZSSD cases, was found in compound heterozygous state in three HS families.
    [Show full text]
  • International Journal of Dentistry and Oral Health Volume 4 Issue 10, September 2018
    International Journal of Dentistry and Oral Health Volume 4 Issue 10, September 2018 International Journal of Dentistry and Oral Health Case Report ISSN 2471-657X Amelogenesis Imperfecta in Primary Dentition-A Case of Full Mouth Rehabilitation Revathy Viswanathan1, Janak Harish Kumar*2, Suganthi3 1Department of Pedodontics, Tamilnadu Government Dental College and Hospital, Chennai, Tamilnadu, India 2Intern, Department of Pedodontics, Tamilnadu Government Dental College and Hospital, Chennai, Tamilnadu, India 3Department of Pedodontics, Tamilnadu Government Dental College and Hospital, Chennai, Tamilnadu, India Abstract The most common anomalies of dental hard tissues include hereditary defects of enamel. Amelogenesis imperfecta (AI) has been described as a complex group of hereditary conditions that disturbs the developing enamel and exists independent of any related systemic disorder. This clinical case report describes the diagnosis and management of hypoplastic amelogenesis imperfecta in a 5-year-old child. The treatment objectives were to improve aesthetics, improve periodontal health, prevent further loss of tooth structure, and improve the child’s confidence. The treatment plan was to restore the affected teeth with full coverage restorations. Treatment involved placement of composite strip crowns on maxillary anterior teeth and stainless steel crowns on the posterior teeth followed by fluoride varnish application in the upper and lower arches. A 6-month follow-up showed great aesthetic and psychological improvements in the patient. Keywords: Amelogenesis imperfecta, Deciduous dentition, Composite strip crowns, Stainless steel crowns Corresponding author: Janak Harish Kumar teeth and can occur in both primary and permanent dentition which Intern, Department of Pedodontics and Preventive dentistry, results in the teeth being small, pitted, grooved and fragile with Tamilnadu Government Dental College and Hospital, Chennai, India.
    [Show full text]
  • Abstracts from the 50Th European Society of Human Genetics Conference: Electronic Posters
    European Journal of Human Genetics (2019) 26:820–1023 https://doi.org/10.1038/s41431-018-0248-6 ABSTRACT Abstracts from the 50th European Society of Human Genetics Conference: Electronic Posters Copenhagen, Denmark, May 27–30, 2017 Published online: 1 October 2018 © European Society of Human Genetics 2018 The ESHG 2017 marks the 50th Anniversary of the first ESHG Conference which took place in Copenhagen in 1967. Additional information about the event may be found on the conference website: https://2017.eshg.org/ Sponsorship: Publication of this supplement is sponsored by the European Society of Human Genetics. All authors were asked to address any potential bias in their abstract and to declare any competing financial interests. These disclosures are listed at the end of each abstract. Contributions of up to EUR 10 000 (ten thousand euros, or equivalent value in kind) per year per company are considered "modest". Contributions above EUR 10 000 per year are considered "significant". 1234567890();,: 1234567890();,: E-P01 Reproductive Genetics/Prenatal and fetal echocardiography. The molecular karyotyping Genetics revealed a gain in 8p11.22-p23.1 region with a size of 27.2 Mb containing 122 OMIM gene and a loss in 8p23.1- E-P01.02 p23.3 region with a size of 6.8 Mb containing 15 OMIM Prenatal diagnosis in a case of 8p inverted gene. The findings were correlated with 8p inverted dupli- duplication deletion syndrome cation deletion syndrome. Conclusion: Our study empha- sizes the importance of using additional molecular O¨. Kırbıyık, K. M. Erdog˘an, O¨.O¨zer Kaya, B. O¨zyılmaz, cytogenetic methods in clinical follow-up of complex Y.
    [Show full text]
  • Volving Periodontal Attachment, the Apposition of Fire Or Severe Trauma, Physical Features Are Often Cementum at the Root Apex, the Amount of Apical Destroyed
    ISSN 0976-2256 E-ISSN: 2249-6653 The journal is indexed with ‘Indian Science Abstract’ (ISA) (Published by National Science Library), www.ebscohost.com, www.indianjournals.com JADCH is available (full text) online: Website- www.adc.org.in/html/viewJournal.php This journal is an official publication of Ahmedabad Dental College and Hospital, published bi-annually in the month of March and September. The journal is printed on ACID FREE paper. Editor - in - Chief Dr. Darshana Shah Co - Editor Dr. Rupal Vaidya DENTISTRY TODAY... Assistant Editor: We are living in an era in which community experience for Dr. Harsh Shah students is becoming a more essential component to the mission of dental education. Dental Public Health aims to improve the oral health of the population through preventive and curative services. The Editorial Board: introduction of mobile clinics into dentistry dates back to 1924. They have Dr. Mihir Shah been successfully used to provide dental treatment to schools, disabled patients, rural communities, industries and armed forces of various Dr. Vijay Bhaskar countries. Outreach programs using Mobile Dental Vans (MDV) are desirable model of clinical practice in a non-conventional setting, and help Dr. Monali Chalishazar the student to disassociate the image that best dentistry can only be Dr. A. R. Chaudhary practiced in conventional clinical settings. Confrontation with limited resources and economic barriers to Dr. Neha Vyas dental care for patients requiring more extensive procedures also serve as an additional learning experience in community-based programs. Unlike Dr. Sonali Mahadevia stationary dental clinics, mobile clinics provide greater physical access to dental care for medically underserved populations in poor urban and Dr.
    [Show full text]
  • Review Article Mouse Homologues of Human Hereditary Disease
    I Med Genet 1994;31:1-19 I Review article J Med Genet: first published as 10.1136/jmg.31.1.1 on 1 January 1994. Downloaded from Mouse homologues of human hereditary disease A G Searle, J H Edwards, J G Hall Abstract involve homologous loci. In this respect our Details are given of 214 loci known to be genetic knowledge of the laboratory mouse associated with human hereditary dis- outstrips that for all other non-human mam- ease, which have been mapped on both mals. The 829 loci recently assigned to both human and mouse chromosomes. Forty human and mouse chromosomes3 has now two of these have pathological variants in risen to 900, well above comparable figures for both species; in general the mouse vari- other laboratory or farm animals. In a previous ants are similar in their effects to the publication,4 102 loci were listed which were corresponding human ones, but excep- associated with specific human disease, had tions include the Dmd/DMD and Hprt/ mouse homologues, and had been located in HPRT mutations which cause little, if both species. The number has now more than any, harm in mice. Possible reasons for doubled (table 1A). Of particular interest are phenotypic differences are discussed. In those which have pathological variants in both most pathological variants the gene pro- the mouse and humans: these are listed in table duct seems to be absent or greatly 2. Many other pathological mutations have reduced in both species. The extensive been detected and located in the mouse; about data on conserved segments between half these appear to lie in conserved chromo- human and mouse chromosomes are somal segments.
    [Show full text]
  • Abstracts from the 51St European Society of Human Genetics Conference: Electronic Posters
    European Journal of Human Genetics (2019) 27:870–1041 https://doi.org/10.1038/s41431-019-0408-3 MEETING ABSTRACTS Abstracts from the 51st European Society of Human Genetics Conference: Electronic Posters © European Society of Human Genetics 2019 June 16–19, 2018, Fiera Milano Congressi, Milan Italy Sponsorship: Publication of this supplement was sponsored by the European Society of Human Genetics. All content was reviewed and approved by the ESHG Scientific Programme Committee, which held full responsibility for the abstract selections. Disclosure Information: In order to help readers form their own judgments of potential bias in published abstracts, authors are asked to declare any competing financial interests. Contributions of up to EUR 10 000.- (Ten thousand Euros, or equivalent value in kind) per year per company are considered "Modest". Contributions above EUR 10 000.- per year are considered "Significant". 1234567890();,: 1234567890();,: E-P01 Reproductive Genetics/Prenatal Genetics then compared this data to de novo cases where research based PO studies were completed (N=57) in NY. E-P01.01 Results: MFSIQ (66.4) for familial deletions was Parent of origin in familial 22q11.2 deletions impacts full statistically lower (p = .01) than for de novo deletions scale intelligence quotient scores (N=399, MFSIQ=76.2). MFSIQ for children with mater- nally inherited deletions (63.7) was statistically lower D. E. McGinn1,2, M. Unolt3,4, T. B. Crowley1, B. S. Emanuel1,5, (p = .03) than for paternally inherited deletions (72.0). As E. H. Zackai1,5, E. Moss1, B. Morrow6, B. Nowakowska7,J. compared with the NY cohort where the MFSIQ for Vermeesch8, A.
    [Show full text]
  • Analysis of the COL17A1 in Non-Herlitz Junctional Epidermolysis Bullosa and Amelogenesis Imperfecta
    333-337 29/6/06 12:35 Page 333 INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE 18: 333-337, 2006 333 Analysis of the COL17A1 in non-Herlitz junctional epidermolysis bullosa and amelogenesis imperfecta HIROYUKI NAKAMURA1, DAISUKE SAWAMURA1, MAKI GOTO1, HIDEKI NAKAMURA1, MIYUKI KIDA2, TADASHI ARIGA2, YUKIO SAKIYAMA2, KOKI TOMIZAWA3, HIROSHI MITSUI4, KUNIHIKO TAMAKI4 and HIROSHI SHIMIZU1 1Department of Dermatology, 2Research Group of Human Gene Therapy, Hokkaido University Graduate School of Medicine, Sapporo 060-8638; 3Department of Dermatology, Ebetsu City Hospital, Hokkaido; 4Department of Dermatology, Faculty of Medicine, University of Tokyo, Tokyo, Japan Received January 31, 2006; Accepted March 27, 2006 Abstract. Non-Herlitz junctional epidermolysis bullosa (nH- truncated polypeptide expression and to a milder clinical JEB) disease manifests with skin blistering, atrophy and tooth disease severity in nH-JEB. Conversely, we failed to detect enamel hypoplasia. The majority of patients with nH-JEB any pathogenic COL17A1 defects in AI patients, in either harbor mutations in COL17A1, the gene encoding type XVII exon or within the intron-exon borders of AI patients. This collagen. Heterozygotes with a single COL17A1 mutation, nH- study furthers the understanding of mutations in COL17A1 JEB defect carriers, may exhibit only enamel hypoplasia. In causing nH-JEB, and clearly demonstrates that the mechanism this study, to further elucidate COL17A1 mutation phenotype/ of enamel hypoplasia differs between nH-JEB and AI genotype correlations, we examined two unrelated families diseases. with nH-JEB. Furthermore, we hypothesized that COL17A1 mutations might underlie or worsen the enamel hypoplasia seen Introduction in amelogenesis imperfecta (AI) patients that are characterized by defects in tooth enamel formation without other systemic Type XVII collagen, 180-kDa bullous pemphigoid antigen is manifestations.
    [Show full text]
  • Amelogenesis Imperfecta
    Amelogenesis imperfecta Description Amelogenesis imperfecta is a disorder of tooth development. This condition causes teeth to be unusually small, discolored, pitted or grooved, and prone to rapid wear and breakage. Other dental abnormalities are also possible. These defects, which vary among affected individuals, can affect both primary (baby) teeth and permanent (adult) teeth. Researchers have described at least 14 forms of amelogenesis imperfecta. These types are distinguished by their specific dental abnormalities and by their pattern of inheritance. Additionally, amelogenesis imperfecta can occur alone without any other signs and symptoms or it can occur as part of a syndrome that affects multiple parts of the body. Frequency The exact incidence of amelogenesis imperfecta is uncertain. Estimates vary widely, from 1 in 700 people in northern Sweden to 1 in 14,000 people in the United States. Causes Mutations in the AMELX, ENAM, MMP20, and FAM83H genes can cause amelogenesis imperfecta. The AMELX, ENAM, and MMP20 genes provide instructions for making proteins that are essential for normal tooth development. Most of these proteins are involved in the formation of enamel, which is the hard, calcium-rich material that forms the protective outer layer of each tooth. Although the function of the protein produced from the FAM83H gene is unknown, it is also believed to be involved in the formation of enamel. Mutations in any of these genes result in altered protein structure or prevent the production of any protein. As a result, tooth enamel is abnormally thin or soft and may have a yellow or brown color. Teeth with defective enamel are weak and easily damaged.
    [Show full text]
  • Oral Pathology Final Exam Review Table Tuanh Le & Enoch Ng, DDS
    Oral Pathology Final Exam Review Table TuAnh Le & Enoch Ng, DDS 2014 Bump under tongue: cementoblastoma (50% 1st molar) Ranula (remove lesion and feeding gland) dermoid cyst (neoplasm from 3 germ layers) (surgical removal) cystic teratoma, cyst of blandin nuhn (surgical removal down to muscle, recurrence likely) Multilocular radiolucency: mucoepidermoid carcinoma cherubism ameloblastoma Bump anterior of palate: KOT minor salivary gland tumor odontogenic myxoma nasopalatine duct cyst (surgical removal, rare recurrence) torus palatinus Mixed radiolucencies: 4 P’s (excise for biopsy; curette vigorously!) calcifying odontogenic (Gorlin) cyst o Pyogenic granuloma (vascular; granulation tissue) periapical cemento-osseous dysplasia (nothing) o Peripheral giant cell granuloma (purple-blue lesions) florid cemento-osseous dysplasia (nothing) o Peripheral ossifying fibroma (bone, cartilage/ ossifying material) focal cemento-osseous dysplasia (biopsy then do nothing) o Peripheral fibroma (fibrous ct) Kertocystic Odontogenic Tumor (KOT): unique histology of cyst lining! (see histo notes below); 3 important things: (1) high Multiple bumps on skin: recurrence rate (2) highly aggressive (3) related to Gorlin syndrome Nevoid basal cell carcinoma (Gorlin syndrome) Hyperparathyroidism: excess PTH found via lab test Neurofibromatosis (see notes below) (refer to derm MD, tell family members) mucoepidermoid carcinoma (mixture of mucus-producing and squamous epidermoid cells; most common minor salivary Nevus gland tumor) (get it out!)
    [Show full text]
  • Jassim Phd Proposal
    A pilot study of the genotype and phenotype in Amelogenesis Imperfecta and Molar Incisor Hypomineralization Submitted in partial fulfillment of the requirements for the Degree of Doctor of Dentistry (Paediatric Dentistry) UCL Mashael Abdullatif Postgraduate (D Dent) Programme Supervisors: Dr Susan Parekh (Paediatric Dentistry) Dr Laurent Bozec (Biophysics and Tissue Engineering) Dr Peter Brett (Genetics) UCL Eastman Dental Institute, 256 Gray’s Inn Road, London WC1X8LD UK 2012 1 ABSTRACT Background Enamel is an external layer of the crown, and its production can be affected by genetic, systemic or environmental causes Amelogenesis Imperfecta (AI) is an inherited defect of dental enamel, and can be autosomal dominant, recessive, x-linked or sporadic. It can present as hypoplasia, hypomineralization or both. Mutations in several genes can cause defective enamel formation and have been linked to AI, e.g: AMELX (amelogenin), ENAM (enamelin), MMP20 (enamelysin) and KLK4 (kallikrein 4), although the correlation between genotype and phenotype is poorly understood. Molar Incisal Hypomineralization (MIH) is defined as an environmentally caused enamel defect of one to four permanent first molars, frequently associated with affected incisors, although the aetiology is unknown. The presence of MIH in siblings, and lack of obvious systemic cause suggests there may be an underlying genetic defect involved. When a patient presents in the early mixed dentition, it can be difficult to distinguish between AI and MIH in the absence of a clear family or medical history. Better understanding of the relationship between phenotype and genotype is required to aid diagnoses and management of these conditions. A pilot study was set up to determine the best method to collect data from patients, and establish a database to record dental anomalies.
    [Show full text]
  • The Alter Retina: Alternative Splicing of Retinal Genes in Health and Disease
    International Journal of Molecular Sciences Review The Alter Retina: Alternative Splicing of Retinal Genes in Health and Disease Izarbe Aísa-Marín 1,2 , Rocío García-Arroyo 1,3 , Serena Mirra 1,2 and Gemma Marfany 1,2,3,* 1 Departament of Genetics, Microbiology and Statistics, Avda. Diagonal 643, Universitat de Barcelona, 08028 Barcelona, Spain; [email protected] (I.A.-M.); [email protected] (R.G.-A.); [email protected] (S.M.) 2 Centro de Investigación Biomédica en Red Enfermedades Raras (CIBERER), Instituto de Salud Carlos III (ISCIII), Universitat de Barcelona, 08028 Barcelona, Spain 3 Institute of Biomedicine (IBUB, IBUB-IRSJD), Universitat de Barcelona, 08028 Barcelona, Spain * Correspondence: [email protected] Abstract: Alternative splicing of mRNA is an essential mechanism to regulate and increase the diversity of the transcriptome and proteome. Alternative splicing frequently occurs in a tissue- or time-specific manner, contributing to differential gene expression between cell types during development. Neural tissues present extremely complex splicing programs and display the highest number of alternative splicing events. As an extension of the central nervous system, the retina constitutes an excellent system to illustrate the high diversity of neural transcripts. The retina expresses retinal specific splicing factors and produces a large number of alternative transcripts, including exclusive tissue-specific exons, which require an exquisite regulation. In fact, a current challenge in the genetic diagnosis of inherited retinal diseases stems from the lack of information regarding alternative splicing of retinal genes, as a considerable percentage of mutations alter splicing Citation: Aísa-Marín, I.; or the relative production of alternative transcripts. Modulation of alternative splicing in the retina García-Arroyo, R.; Mirra, S.; Marfany, is also instrumental in the design of novel therapeutic approaches for retinal dystrophies, since it G.
    [Show full text]