DOCSLIB.ORG

The Role of Inheritance and the Care of Children

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
The Role of Inheritance and the Care of Children CHAPTER 2 PAEDIATRICS AND GENETICS THE ROLE OF INHERITANCE AND THE CARE OF CHILDREN Paediatrics and Genetics 21 Dry skin – the sort that itches, peels, flakes or cracks in cold weather – is extremely common. As many as one in ten of the population – five to ten million people – suffer from it at some stage. The cosmetics industry, with its emollient creams and lotions, is founded on it. Some people have a more serious condition known as ichthyosis in which the skin is dry, thickened and scaly. Ichthyosis is derived from the Ichthyosis Ichthyosis Vulgaris Lichen Sclerosus Chromosome Mutation Greek, meaning “fish scales”, a reference to the characteristic appearance of the skin. The commonest type, accounting for 95 per cent of cases, is ichthyosis vulgaris which affects an estimated 800,000 people in Britain. It is mostly mild and in many cases mistaken for normal dry skin but rare types of ichthyosis can be severe and even life threatening. Ichthyosis is a genetic skin disease, passed down the generations. There are an estimated 5,000 genetic diseases in all, of which around one third One in ten people – five to ten million – suffer from dry skin but some have a more serious conditions. Ichthyosis Vulgaris (left) affects around 800,000 people in Britain and Lichen Sclerosis (right) affects 200,000 involve the skin. The best hope for patients suffering from these diseases is to identify the gene sclerosus , which affects one in 300 people. The 3 1 3 1 3 2 2 2 2 1 2 2 2 1 2 . 3 2 1 2 4 3 2 4 2 5 1 4 1 1 5 (or genes) that is the culprit and to develop a breakthrough in understanding led to new . q q q 4 1 3 3 6 2 3 2 2 3 3 6 1 1 q 1 p p p q 3 q q p p p 3 1 1 1 1 p 1 1 1 1 1 1 p 1 therapy based on that. approaches to treating both diseases. 1 2 3 1 2 2 1 3 2 3 2 2 3 2 2 3 . 1 1 4 1 2 3 2 4 2 . 4 1 3 1 1 1 . q p p 3 2 3 That is the task of the Paediatrics and Genetics Professor McGrath and colleagues have since 6 2 2 3 2 2 2 3 6 1 q 1 1 p p 3 q q q q p p 4 3 1 1 1 p q 1 1 1 1 1 1 p 1 1 department headed by Professor John McGrath . He discovered several single gene mutations that are 1 The gene that causes lipoid proteinosis: ECM1 is a gene hunter with a collection of scalps on his the cause of other skin diseases and opened the belt. To take one example, he and his team way for the development of new and more effective Today, the St John’s clinic is designated as a investigated lipoid proteinosis , a rare condition therapies. national centre for the treatment of highly affecting one in 300,000 people which causes At the same time the clinical service of paediatric specialised paediatric skin disease. Last year, under scarring and infiltration (thickening and hardening dermatology offered at St John’s has expanded consultant dermatologist Jemima Mellerio , it saw of the skin) and found the gene that caused it, rapidly since the mid-2000s. Prior to 2007, there 2,000 patients. ECM1 (extracellular matrix protein 1). Working on was one paediatric clinic a month for the severest “Until 2007, we used to get the children, babies this protein, he then found a link to a much more cases run by a consultant from Great Ormond Street with eczema and all the rest and put them in with common inflammatory skin condition, lichen Hospital for Sick Children. the adults. Now that seems extraordinary,” she said. 22 Paediatrics and Genetics CHAPTER 2 PAEDIATRICS AND GENETICS History John McGrath Geoffrey Dowling Bob Meara George Wells Robin Eady at work in the 1960s The origins of St John’s expertise in genetics can be Geoffrey Dowling , consultant and director of EB and ichthyosis. He was also an inspirational traced back to the 1950s when dermatologists from St Johns from 1951-56, described with registrar Bob teacher, raised money to upgrade the dermatology around London used to meet at the hospital, then in Meara a form of the blistering skin disease section of Guy’s medical museum to become a Lisle Street, to discuss unusual cases. “It was the Epidermolysis Bullosa (EB, see below) since called “teaching laboratory” and by the early 1980s St collection of these cases and their careful Dowling-Meara EB simplex . John’s was producing one quarter of all the description that laid the groundwork for future R S Wells – known as Charlie – developed dermatologists in the country. advance,” said Professor McGrath. prototype classifications for the different types of By then Robin Eady , another pioneer, was using Healthy Skin EB Hemidesmosome plaque EB Simplex a6ß4 integrin Epidermis Collagen Anchoring Laminin 5 Lamina lucida XVII Filaments Dermis Lamina densa Junctional Subcutaneous EB tissue Muscles Type VII collagen Anchoring Fibrils Sublima densa Dystrophic EB The development of the blistering skin disease Epidermolysis Bullosa Paediatrics and Genetics 23 electron microscopy to see inside cells and inspect whether to seek a termination. It would have been Signal their structure. It was a long laborious process, but far better to make the diagnosis before the mother Fluorescent Tag it led ultimately to quicker diagnosis through the became pregnant. introduction of immunohistochemistry (staining With the development of single cell polymerase Labeled Secondary techniques), reducing the wait for results from three chain reaction (PCR) technology , which could Antibody weeks to three days. amplify a single piece of DNA by several orders of Primary Antibody Eady, working with obstetricians, also pioneered magnitude, pre-natal diagnosis became possible in Proteins the development of foetal skin biopsy – taking tiny the late 1990s. Parents could opt for in-vitro skin samples from babies in the womb to examine fertilisation (IVF) with pre-implantation diagnosis to for EB. The test was offered to parents who already select unaffected embryos for replacement in the had an affected child to give them the option of a womb. It was the natural extension of Eady’s work Cell/ Tissue termination. But the biopsy could not be done until Eady, who was awarded an MBE in the New Year 16 weeks, very late in the pregnancy. Foetal skin Honours 2014, was also a pioneer in a different way. Signal biopsy has now largely been superseded by He is the world’s longest surviving kidney failure Fluorescent Tag chorionic villus sampling , taking a tiny sample from patient, at the time of writing, who as a medical the placenta, which is carried out at 10-11 weeks student in 1963 flew to North America for Labeled Primary and has already been applied to over 400 couples treatment. He was so weak he had to be carried off Light Antibody Proteins at St John’s. the Boeing 707. He spent 24 years on dialysis and Nevertheless, this still left parents carrying an the last 26 with a kidney transplant. affected baby facing the heartrending decision of Cell/ Tissue Indirect immunohistochemistry and immunofluorescence methods Pre-natal diagnosis of certain skin diseases became possible with the development of polymerase chain reaction (PCR) technology Polymerase chain reaction - PCR original DNA to be replied 5´ 3´ 5´ 3´ 5´ 3´ 3´ 5´ 5´ 3´ 1 1 1 2 3 2 2 3 3 3´ 5´ 5´ 3´ 3´ 5´ DNA primer 3´ 5´ 3´ 5´ nucleotide 24 Paediatrics and Genetics CHAPTER 2 PAEDIATRICS AND GENETICS Genetic breakthrough Plakophilin 1 Protein “It was going through the analyser and I could see there was an exciting mutation. It was a Eureka moment. We had discovered a new disease” – Professor John McGrath Intercellular space Desmosome In 1995, McGrath, who returned to St John’s from a in 1997 the condition subsequently became Plaque sojourn in the US, began his gene hunting in earnest. recognised as a form of EB . He established a molecular diagnostics laboratory Over the next 15 years, McGrath examined the and raised money for an automated gene sequencer, structure, function and protein composition of then regarded as a “new-fangled” piece of kit. As it was being installed, McGrath pulled a tissue sample from his “special bottom draw” of mystery patients, to use as a test. Intermediate filament Special Characteristics of Epithelia-Cell Junction Linker glycoproteins “It was going through the analyser and I could (keratin) see the company technician frowning. He thought Microvilli Desmosomes: there was a malfunction. But I could see something Narrow Apical region of an Anchoring exciting was unfolding - there was an exciting Cillia extracellular junctions bind space epithelian cell frame-shift mutation. It was a Eureka moment – we adjacent cells together and help had found a new disease.” Cell junctions form an internal The sample in the sequencer was from a patient Tight junction tension-reducing Adhesive belt network of fibers. with ectodermal dysplasia -skin fragility syndrome Desmosome and it had revealed the cause to be a demosomal Gap junction gene disorder resulting from a mutation in Basal region Basement plakophilin 1 . It was the world’s first genetic Basal lamina Nerve ending Reticular fibers membrane disorder of cell attachment complexes called desmosomes . After McGrath published his findings Capillary Paediatrics and Genetics 25 1 2 tissue samples from a range of patients to gain some idea of what was going wrong in order to target the search for the genetic culprit with what is known as the “candidate gene” approach.
Load more

Recommended publications
  • Ectodermal Dysplasias: a New Clinical-Genetic Classification
    J Med Genet 2001;38:579–585 579 Ectodermal dysplasias: a new clinical-genetic J Med Genet: first published as 10.1136/jmg.38.9.579 on 1 September 2001. Downloaded from classification Manuela Priolo, Carmelo Laganà Abstract many case reports and personal communica- The ectodermal dysplasias (EDs) are a tions in their listing of EDs, as well as large and complex nosological group of conditions traditionally classified under other diseases, first described by Thurnam in headings, for example dyskeratosis congenita11 1848. In the last 10 years more than 170 and keratitis-ichthyosis-deafness (KID) syn- diVerent pathological clinical conditions drome12 (poikiloderma and immune defect have been recognised and defined as EDs, diseases and erythrokeratodermas, respec- all sharing in common anomalies of the tively). Further, they did not appear to hair, teeth, nails, and sweat glands. Many consider variability of expression and may are associated with anomalies in other have reported, as distinct diseases, conditions organs and systems and, in some condi- that reflect variable expression of the same tions, with mental retardation. pathological entity. Moreover, they included The anomalies aVecting the epidermis pathological conditions which, in our opinion, and epidermal appendages are extremely do not strictly fulfil the diagnostic criteria for variable and clinical overlap is present EDs, such as conditions with secondary among the majority of EDs. Most EDs are involvement of epidermal derivatives rather defined by particular clinical signs (for than a primary defect. We abandoned the 1-2- example, eyelid adhesion in AEC syn- 3-4 designation of EDs, because we believe drome, ectrodactyly in EEC).
    [Show full text]
  • Bilateral Lower Extremity Hyperkeratotic Plaques: a Case Report of Ichthyosis Vulgaris
    Faculty & Staff Scholarship 2015 Bilateral lower extremity hyperkeratotic plaques: a case report of ichthyosis vulgaris Hayley Leight Zachary Zinn Omid Jalali Follow this and additional works at: https://researchrepository.wvu.edu/faculty_publications Clinical, Cosmetic and Investigational Dermatology Dovepress open access to scientific and medical research Open Access Full Text Article CASE REPORT Bilateral lower extremity hyperkeratotic plaques: a case report of ichthyosis vulgaris Hayley Leight Abstract: Here, we report a case of a middle-aged woman presenting with severe, long-standing, Zachary Zinn hyperkeratotic plaques of the lower extremities unrelieved by over-the-counter medications. Omid Jalali Initial history and clinical findings were suggestive of an inherited ichthyosis. Ichthyoses are genetic disorders characterized by dry scaly skin and altered skin-barrier function. A diagnosis Department of Dermatology, West Virginia University, of ichthyosis vulgaris was confirmed by histopathology. Etiology, prevalence, and treatment Morgantown, WV, USA options are discussed. Keywords: filaggrin gene, FLG, profilaggrin, keratohyalin granules, hyperkeratosis Introduction For personal use only. Inherited ichthyoses are a diverse group of genetic disorders characterized by dry, scaly skin; hyperkeratosis; and altered skin-barrier function. While these disorders of cutaneous keratinization are multifaceted and varying in etiology, disruption in the stratum corneum with generalized scaling is common to all.1–4 Although not entirely known
    [Show full text]
  • Blueprint Genetics Ectodermal Dysplasia Panel
    Ectodermal Dysplasia Panel Test code: DE0401 Is a 25 gene panel that includes assessment of non-coding variants. Is ideal for patients with a clinical suspicion of ectodermal dysplasia (hidrotic or hypohidrotic) or Ellis-van Creveld syndrome. About Ectodermal Dysplasia Ectodermal Dysplasia (ED) is a group of closely related conditions of which more than 150 different syndromes have been identified. EDs affects the development or function of teeth, hair, nails and sweat glands. ED may present as isolated or as part of a syndromic disease and is commonly subtyped according to sweating ability. The clinical features of the X-linked and autosomal forms of hypohidrotic ectodermal dysplasia (HED) can be indistinguishable and many of the involved genes may lead to phenotypically distinct outcomes depending on number of defective alleles. The most common EDs are hypohidrotic ED and hydrotic ED. X-linked hypohidrotic ectodermal dysplasia (HED) is caused by EDA mutations and explain 75%-95% of familial HED and 50% of sporadic cases. HED is characterized by three cardinal features: hypotrichosis (sparse, slow-growing hair and sparse/missing eyebrows), reduced sweating and hypodontia (absence or small teeth). Reduced sweating poses risk for episodes of hyperthermia. Female carriers may have some degree of hypodontia and mild hypotrichosis. Isolated dental phenotypes have also been described. Mutations in WNT10A have been reported in up to 9% of individuals with HED and in 25% of individuals with HED who do not have defective EDA. Approximately 50% of individuals with heterozygous WNT10A mutation have HED and the most consistent clinical feature is severe oligodontia of permanent teeth.
    [Show full text]
  • MECHANISMS in ENDOCRINOLOGY: Novel Genetic Causes of Short Stature
    J M Wit and others Genetics of short stature 174:4 R145–R173 Review MECHANISMS IN ENDOCRINOLOGY Novel genetic causes of short stature 1 1 2 2 Jan M Wit , Wilma Oostdijk , Monique Losekoot , Hermine A van Duyvenvoorde , Correspondence Claudia A L Ruivenkamp2 and Sarina G Kant2 should be addressed to J M Wit Departments of 1Paediatrics and 2Clinical Genetics, Leiden University Medical Center, PO Box 9600, 2300 RC Leiden, Email The Netherlands [email protected] Abstract The fast technological development, particularly single nucleotide polymorphism array, array-comparative genomic hybridization, and whole exome sequencing, has led to the discovery of many novel genetic causes of growth failure. In this review we discuss a selection of these, according to a diagnostic classification centred on the epiphyseal growth plate. We successively discuss disorders in hormone signalling, paracrine factors, matrix molecules, intracellular pathways, and fundamental cellular processes, followed by chromosomal aberrations including copy number variants (CNVs) and imprinting disorders associated with short stature. Many novel causes of GH deficiency (GHD) as part of combined pituitary hormone deficiency have been uncovered. The most frequent genetic causes of isolated GHD are GH1 and GHRHR defects, but several novel causes have recently been found, such as GHSR, RNPC3, and IFT172 mutations. Besides well-defined causes of GH insensitivity (GHR, STAT5B, IGFALS, IGF1 defects), disorders of NFkB signalling, STAT3 and IGF2 have recently been discovered. Heterozygous IGF1R defects are a relatively frequent cause of prenatal and postnatal growth retardation. TRHA mutations cause a syndromic form of short stature with elevated T3/T4 ratio. Disorders of signalling of various paracrine factors (FGFs, BMPs, WNTs, PTHrP/IHH, and CNP/NPR2) or genetic defects affecting cartilage extracellular matrix usually cause disproportionate short stature.
    [Show full text]
  • Practice Parameter for the Diagnosis and Management of Primary Immunodeficiency
    Practice parameter Practice parameter for the diagnosis and management of primary immunodeficiency Francisco A. Bonilla, MD, PhD, David A. Khan, MD, Zuhair K. Ballas, MD, Javier Chinen, MD, PhD, Michael M. Frank, MD, Joyce T. Hsu, MD, Michael Keller, MD, Lisa J. Kobrynski, MD, Hirsh D. Komarow, MD, Bruce Mazer, MD, Robert P. Nelson, Jr, MD, Jordan S. Orange, MD, PhD, John M. Routes, MD, William T. Shearer, MD, PhD, Ricardo U. Sorensen, MD, James W. Verbsky, MD, PhD, David I. Bernstein, MD, Joann Blessing-Moore, MD, David Lang, MD, Richard A. Nicklas, MD, John Oppenheimer, MD, Jay M. Portnoy, MD, Christopher R. Randolph, MD, Diane Schuller, MD, Sheldon L. Spector, MD, Stephen Tilles, MD, Dana Wallace, MD Chief Editor: Francisco A. Bonilla, MD, PhD Co-Editor: David A. Khan, MD Members of the Joint Task Force on Practice Parameters: David I. Bernstein, MD, Joann Blessing-Moore, MD, David Khan, MD, David Lang, MD, Richard A. Nicklas, MD, John Oppenheimer, MD, Jay M. Portnoy, MD, Christopher R. Randolph, MD, Diane Schuller, MD, Sheldon L. Spector, MD, Stephen Tilles, MD, Dana Wallace, MD Primary Immunodeficiency Workgroup: Chairman: Francisco A. Bonilla, MD, PhD Members: Zuhair K. Ballas, MD, Javier Chinen, MD, PhD, Michael M. Frank, MD, Joyce T. Hsu, MD, Michael Keller, MD, Lisa J. Kobrynski, MD, Hirsh D. Komarow, MD, Bruce Mazer, MD, Robert P. Nelson, Jr, MD, Jordan S. Orange, MD, PhD, John M. Routes, MD, William T. Shearer, MD, PhD, Ricardo U. Sorensen, MD, James W. Verbsky, MD, PhD GlaxoSmithKline, Merck, and Aerocrine; has received payment for lectures from Genentech/ These parameters were developed by the Joint Task Force on Practice Parameters, representing Novartis, GlaxoSmithKline, and Merck; and has received research support from Genentech/ the American Academy of Allergy, Asthma & Immunology; the American College of Novartis and Merck.
    [Show full text]
  • Significant Absorption of Topical Tacrolimus in 3 Patients with Netherton Syndrome
    OBSERVATION Significant Absorption of Topical Tacrolimus in 3 Patients With Netherton Syndrome Angel Allen, MD; Elaine Siegfried, MD; Robert Silverman, MD; Mary L. Williams, MD; Peter M. Elias, MD; Sarolta K. Szabo, MD; Neil J. Korman, MD, PhD Background: Tacrolimus is a macrolide immunosup- limus in organ transplant recipients. None of these pressant approved in oral and intravenous formulations patients developed signs or symptoms of toxic effects of for primary immunosuppression in liver and kidney trans- tacrolimus. plantation. Topical 0.1% tacrolimus ointment has re- cently been shown to be effective in atopic dermatitis for Conclusions: Patients with Netherton syndrome have children as young as 2 years of age, with minimal sys- a skin barrier dysfunction that puts them at risk for in- temic absorption. We describe 3 patients treated with topi- creased percutaneous absorption. The Food and Drug Ad- cal 0.1% tacrolimus who developed significant systemic ministration recently approved 0.1% tacrolimus oint- absorption. ment for the treatment of atopic dermatitis. Children with Netherton syndrome may be misdiagnosed as having Observation: Three patients previously diagnosed as atopic dermatitis. These children are at risk for marked having Netherton syndrome were treated at different cen- systemic absorption and associated toxic effects. If topi- ters with 0.1% tacrolimus ointment twice daily. Two pa- cal tacrolimus is used in this setting, monitoring of se- tients showed dramatic improvement. All patients were rum tacrolimus levels is essential. found to have tacrolimus blood levels within or above the established therapeutic trough range for oral tacro- Arch Dermatol. 2001;137:747-750 ETHERTON syndrome is taneous absorption of the drug, with serum an autosomal recessive levels well above the therapeutic range.
    [Show full text]
  • Chronic Diarrhea in an Adolescent Girl with a Genetic Skin Condition
    PHOTO CHALLENGE Chronic Diarrhea in an Adolescent Girl With a Genetic Skin Condition Lucia Liao, BS; Andrea Zaenglein, MD; Galen T. Foulke, MD A 17-year-old adolescent girl visited our clinic to establish care for her genetic skin condition. She exhibited red scaly plaques and patches over much of the body surface area consistent with atopic dermatitis but also had areas on the trunk with serpiginous red plaques with scale on the leading and trailingcopy edges. She also noted fragile hair with sparse eyebrows. The patient reported that she had experienced chronic diarrhea and abdominal pain since childhood. She asked if it couldnot be related to her genetic condition. WHAT’S THE DIAGNOSIS? a. dyskeratosis follicularis (Darier disease) b. elastosis perforans serpiginosa Doc. erythema marginatum d. Netherton syndrome e. subacute cutaneous lupus erythematosus PLEASE TURN TO PAGE E19 FOR THE DIAGNOSIS CUTIS Ms. Liao is from Pennsylvania State University College of Medicine, Hershey. Drs. Zaenglein and Foulke are from the Department of Dermatology, Pennsylvania State Medical Center, Hershey. Dr. Zaengelin also is from the Department of Pediatrics. The authors report no conflict of interest. Correspondence: Galen T. Foulke, MD, 500 University Dr HU14, Hershey, PA 17033 ([email protected]). E18 I CUTIS® WWW.MDEDGE.COM/DERMATOLOGY Copyright Cutis 2020. No part of this publication may be reproduced, stored, or transmitted without the prior written permission of the Publisher. PHOTO CHALLENGE DISCUSSION THE DIAGNOSIS: Netherton Syndrome
    [Show full text]
  • Proceedings of the 16Th Annual Meeting of the Society for Pediatric Dermatoiogy
    SPECIAL ARTICLE Pediatric Dermatology Vol. 9 No. 1 66-76 Proceedings of the 16th Annual Meeting of the Society for Pediatric Dermatoiogy WiUiamsburg, Virginia June 3a-July 3, 1991 Eleanor £. Sahn, M.D. Medical University of South Carolina Charleston, South Carolina A. Howiand Hartley, M.D. Children's Hospital National Medical Center Washington, D.C. Stephen Gellis, M.D. Children's Hospital Medical Center Boston, Massachusetts James E. Rasmussen, M.D. University of Michigan Medical Center Ann Arbor, Michigan Monday, July 1, 1991 ture by the newspaper account he received, dated December 17, 1799, telling of General George Dr. Alfred T. Lane (Stanford University) orga- Washington's death. We learn the story of General nized the sixteenth annual meeting of the Society Washington's rapid demise, probably from bacterial for Pediatric Dermatology, held in Wiliiamsburg, infection, hastened by the medical treatments of the Virgitiia. The seventh annual Sidney Hurwitz Lec- day, including frequent and copious blood letting. ture was delivered by Dr. Rona M. MacKie (Uni- There was a current saying, "more people died an- versity of Glasgow) on "Melanoma: Risk Factors in nually from lancets than from swords." Dysplastic Nevus Syndrome." President Anne Lucky (Cincinnati, Ohio) welcomed the society MELANOMA: RISK FACTORS AND members to Wiliiamsburg and introduced the first DYSPLASTIC NEVUS SYNDROME speaker. Dr. Rona MacKie first discussed risk factors in mel- anoma, citing several large case control studies car- COLONIAL MEDICINE ried out in western Canada, Scotland, Scandinavia, Dr. Tor A. Shwayder (Henry Ford Hospital) pre- and Germany. The frequency of melanoma has dou- sented a delightful and professional "Character In- bled each decade in Scandinavia, the United King- terpreter Portrayal of Iseiac Shwayder, Medical dom, and Germany.
    [Show full text]
  • CORPORATE PRESENTATION Q3 2020 Forward-Looking Statements
    Medicines for Rare Diseases – A Gene Therapy Company CORPORATE PRESENTATION Q3 2020 Forward-Looking Statements This presentation contains forward-looking statements that involve substantial risks and uncertainties. Any statements in this presentation about future expectations, plans and prospects for Krystal Biotech, Inc. (the “Company”), including but not limited to statements about the development of the Company’s product candidates, such as the future development or commercialization of B-VEC, KB105 and the Company’s other product candidates; conduct and timelines of clinical trials, the clinical utility of B-VEC, KB105 and the Company’s other product candidates; plans for and timing of the review of regulatory filings, efforts to bring B-VEC, KB105 and the Company’s other product candidates to market; the market opportunity for and the potential market acceptance of B-VEC, KB105 and the Company’s other product candidates, the development of B-VEC, KB105 and the Company’s other product candidates for additional indications; the development of additional formulations of B-VEC, KB105 and the Company’s other product candidates; plans to pursue research and development of other product candidates, the sufficiency of the Company’s existing cash resources; and other statements containing the words “anticipate,” “believe,” “estimate,” “expect,” “intend,” “may,” “plan,” “predict,” “project,” “target,” “potential,” “likely,” “will,” “would,” “could,” “should,” “continue,” and similar expressions, constitute forward-looking statements within the meaning of The Private Securities Litigation Reform Act of 1995. Actual results may differ materially from those indicated by such forward-looking statements as a result of various important factors, including: the content and timing of decisions made by the U.S.
    [Show full text]
  • Mutation and Expression of Abca12in Keratosis Pilaris and Nevus
    MOLECULAR MEDICINE REPORTS 18: 3153-3158, 2018 Mutation and expression of ABCA12 in keratosis pilaris and nevus comedonicus FEN LIU1,2*, YAO YANG1,3*, YAN ZHENG1,3, YAN-HUA LIANG1,3 and KANG ZENG1 1Department of Dermatology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515; 2Department of Histology and Embryology, Institute of Neuroscience, School of Basic Medical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang 325035; 3Department of Dermatology, Shenzhen Hospital, Southern Medical University, Shenzhen, Guangdong 518100, P.R. China Received June 22, 2017; Accepted April 17, 2018 DOI: 10.3892/mmr.2018.9342 Abstract. Keratosis pilaris (KP) and nevus comedonicus Introduction (NC) are congenital keratinized dermatoses; however, the exact etiology of these two diseases is unclear. The objective Keratosis pilaris (KP; OMIM #604093), also known as of the present study was to identify the disease-causing genes lichen pilaris, is a benign genodermatosis that is estimated and their association with functional alterations in the devel- to effect ~40% of the population (1). KP is characterized by opment of KP and NC. Peripheral blood samples of one KP the presence of symmetric, asymptomatic and grouped kera- family, two NC families and 100 unrelated healthy controls totic follicular papules with varying degrees of perifollicular were collected. The genomic sequences of 147 genes associ- erythema. KP lesions often involve the proximal and extended ated with 143 genetic skin diseases were initially analyzed parts of extremities, the cheeks and the buttocks (2). Cases from the KP proband using a custom-designed GeneChip. A may be generalized or unilateral (2). Most patients develop KP novel heterozygous missense mutation in the ATP-binding in their childhood, with a peak in incidence during adoles- cassette sub-family A member 12 (ABCA12) gene, designated cence (3).
    [Show full text]
  • Genodermatoses
    GENODERMATOSES Genodermatoses What’s new? Nigel P Burrows C Filaggrin mutations underlie ichthyosis vulgaris and are a risk factor for atopy including eczema, allergic sensitization, asthma, allergic rhinitis and peanut allergy Abstract C A new classification and nomenclature for ichthyoses was Genetic skin diseases encompass a spectrum from the common to the published in 2009, peeling skin syndromes which may be rare. It is important for the clinician to be alert to the possibility that confused for the milder subtypes of epidermolysis bullosa are the patient may be presenting for the first time with one or more features distinct genetic entities of a genetic disease so that appropriate investigation and counselling can C Emerging evidence that pseudoxanthoma elasticum is a meta- take place. Recent discoveries have helped the understanding of many of bolic disorder resulting in calcification of elastic fibres these disorders. A few common and important genodermatoses are high- C Mammalian target of rapamycin (mTOR) inhibitor therapies are lighted in this article. showing promise in tuberous sclerosis complex C Vascular anomalies on the skin may be the presenting feature of Keywords cancer syndromes; collagen; epidermolysis bullosa; filaggrin; inherited syndromes genodermatoses; ichthyosis; keratinization; pseudoxanthoma elasticum; vascular anomalies X-linked recessive ichthyosis In 75% of cases of X-linked recessive ichthyosis (XLRI) (Figure 1), scaling is present in the first week of life and tends to progress into adolescence. In contrast to IV, the flexures may be Genetic skin diseases encompass a spectrum from the common involved. A third of cases are associated with a prolonged labour. (e.g. atopic eczema) to the rare (e.g.
    [Show full text]
  • Ichthyosis Vulgaris a Case Report and Review of Literature Sarah E
    CASE REPORT Ichthyosis Vulgaris A Case Report and Review of Literature Sarah E. Mertz, Thea D. Nguyen, Lori A. Spies chthyosis vulgaris (IV) is a hereditary skin condi- removal surgery. By patient report, the lesions had been tion characterized by an accumulation of cells in present since childhood but progressively worsened over the horny layer that manifests as xerotic, plate- the past few years because of a lack of skin care routine. As like scales. It is most prominent on the extensor is typical in IV, there was a history of improvement of surfaces of the extremities, back, abdomen, and symptoms in warmer months of the summer. Comorbidities legs and exhibits palmar hyperlinearity (Takeichi & to the long-standing IV and cognitive disability include IAkiyama, 2016). If not properly treated, this build up hypertension and obesity. There was no personal history of can cause difficulty in patient care and a decrease in the skin cancer, and the patient was not able to provide details of quality of life of those afflicted with this condition. his family history. On physical examination, significant and There are more than 20 types of ichthyosis to include pertinent findings include diffuse symmetric, thick, hyper- epidermolytic ichthyosis, congential reticular ichthyosiform keratotic, light-gray, fish-scaled plaques with fissures prom- erythroderma, and lamellar ichthyosis, with IV being the inent on the dorsal and ventral surfaces of the bilateral upper most common type of hereditary nonsyndromic ichthyosis extremities including arms, forearms, dorsal hands, and and characterized as a reduction of keratohyalin granules posterior neck and fine, scaly, erythematous areas of or a granular layer absence (Takeichi & Akiyama, 2016).
    [Show full text]