DOCSLIB.ORG

Is the Loose Anagen Hair Syndrome a Keratin Disorder? a Clinical and Molecular Study

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Is the Loose Anagen Hair Syndrome a Keratin Disorder? a Clinical and Molecular Study STUDY Is the Loose Anagen Hair Syndrome a Keratin Disorder? A Clinical and Molecular Study Vale´rie Chapalain, MD; Hermelita Winter, PhD; Lutz Langbein, PhD; Jean-Michel Le Roy, MD; Christine Labre`ze, MD; Milos Nikolic, MD; Ju¨rgen Schweizer, PhD; Alain Taı¨eb, MD Objectives: To report the clinical features of the loose seldom cut their hair, and 4 had unmanageable hair. One anagen hair syndrome and to test the hypothesis that the patient had hypodontia. Two patients had an additional typical gap between the hair and the inner root sheath clinical phenotype of diffuse partial woolly hair. The fam- may result from hereditary defects in the inner root sheath ily history was positive for loose anagen hair syndrome or the apposed companion layer. in 5 patients. Marked improvement was noted after treat- ment with 5% minoxidil lotion in 7 of the 11 patients Design: Case series. treated. Polymerase chain reaction analysis of the gene segments encoding the ␣-helical 1A and 2B subdomains Setting: A pediatric dermatology unit (referral center). of K6hf, the type II cytokeratin exclusively expressed in the companion layer, was performed in 9 families. In Patients: A consecutive sample of 17 children (13 girls). 3 of these 9 families, a heterozygous glutamic acid and For 9 of them and their first-degree relatives, molecular lysine mutation, E337K, was identified in the L2 linker analyses were performed in the K6HF gene with 50 ap- region of K6HF. propriate controls. Conclusions: Diffuse partial woolly hair can be associ- Intervention: Minoxidil therapy (5% lotion) in 11 pa- ated with loose anagen hair syndrome. A keratin muta- tients for 1 to 12 months. tion, E337K in K6HF, was possibly causative in 3 of the 9 families studied. Another keratin, and possibly the type Main Outcome Measures: Clinical and follow-up fea- I partner of K6hf, could be responsible for loose anagen tures and determination of mutations in the K6HF gene. hair syndrome in other patients, or the gene involved may be a minor gene. Results: Most patients had easily pluckable hair with no sign of scalp inflammation or scarring. Ten patients Arch Dermatol. 2002;138:501-506 INCE 1990, it has been known pulling, to painlessly extract anagen hairs that mutations in keratin genes that lack the inner root sheath (IRS) and can cause various hereditary the outer root sheath. epithelialdisorders.Thedelete- rious mutations are not ran- For editorial comment Sdomly distributed along a keratin molecule, see page 521 From Unite´ de Dermatologie but occur preferentially in those parts of the Pe´diatrique, Hoˆpital molecule that are essential for ordered fila- Previous analyses of hair morpho- Pellegrin-Enfants, Bordeaux, ment formation. The main areas involved in logic features in patients with LAHS have France (Drs Chapalain, Le Roy, this process are the helix initiation motif or shown that the main defect is a gap be- Labre`ze, and Taı¨eb); the the helix termination motif. The hereditary tween the cuticle of the IRS and the cu- German Cancer Research hair disease monilethrix can be caused by ticle of the hair, without abnormalities of Center, Heidelberg, Germany a mutation in hair keratins.1 the hair follicle structure. We hypoth- (Drs Winter, Langbein, and Loose anagen hair syndrome (LAHS) esized that the typical gap between the hair Schweizer); and the is a recently described hair disease, char- and the IRS may result from defects in the Department of Dermatology, acterized by easily pluckable hair. It was IRS or in the apposed companion layer University Hospital, Belgrade, first reported by Zaun in 1984,2 and then (CL). Both compartments are tightly con- Yugoslavia (Dr Nikolic). 3 Dr Taı¨eb is now with the by No¨dl et al in 1986, and was then pub- nected and are thought to stabilize the Service de Dermatologie, lished in the US literature by Hamm and growing hair. Thus, mutations in kerat- Hoˆpital St Andre´, Bordeaux, Traupe4 and Price and Gummer5 in 1989. ins expressed in these follicular compart- France. The essential finding is the ability, by gentle ments may compromise the stable anchor- (REPRINTED) ARCH DERMATOL / VOL 138, APR 2002 WWW.ARCHDERMATOL.COM 501 ©2002 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 09/25/2021 Summary of the Clinical Findings in the 17 Children PATIENTS AND METHODS Variable Findings* Female-male ratio 13:4 PATIENTS Age, y At the initial visit, mean 4.3 (2.0-8.5) From January 1988 to December 1998, 17 cases of (range) LAHS originating from 17 different families were di- At onset Birth to 7 agnosed in our unit because of easily pluckable hair, Family history Positive for LAHS (n = 5) alopecia, and/or slow-growing hairs. The diagnosis Associated findings Hypodontia (n = 1), fragile nails was established on clinical grounds associated with (n = 1), atopic dermatitis (n = 2), a trichogram in 16 patients. More than 50% of dys- and psoriasis guttata (n = 1) trophic anagen hairs in the trichogram was consid- Trichogram (obtained in Mostly dystrophic anagen hairs ered as diagnostic of LAHS in 14 of the 16 patients 16 patients) (n = 14), 56.5%-99.0%; and investigated. associated with DPWH (n = 2) Course of the disease Follow-up, 3.0 mo to 6.5 y (n = 15): DNA natural improvement (n = 10) and stable (n = 5) Minoxidil therapy (5% lotion twice a After ethic committee approval, blood was drawn day), 1 mo to1y(n=11): 7 from consenting affected and unaffected members patients showed improvement of 9 nuclear families (the propositus and parents and sometimes brothers and sisters) of this series *LAHS indicates loose anagen hair syndrome; DPWH, diffuse partial and from 50 unrelated healthy individuals, without woolly hair. a history of hair disorder, to whom the aim and nature of the study had been explained. Genomic tions in these keratins should result in disorders other DNA was isolated (Blood and Tissue Culture DNA Extraction System; QIAGEN GmbH, Hilden, than loose anagen. Germany). We describe 17 consecutive patients with LAHS who were referred to our department from January 1988 to MUTATION ANALYSIS December 1998. For 9 of them and their first-degree rela- tives, molecular analyses were performed in the K6HF The gene segments encoding the ␣-helical 1A and 2B gene to look at possible causative mutations. subdomains of K6HF were amplified by the polymer- ase chain reaction using the primer pairs 5Ј- TCAGTGGCCCCAGCTTCCCCTGTT-3Ј (forward RESULTS primer) and 5Ј-TGTTCCTCAGTTCAGCTTCAA- GCCTGC-3Ј (reverse primer) for amplification of the CLINICAL FINDINGS 1A region and the primer pairs 5Ј-GGCAGGCTT- GAAGCTGAACTGAGGA-3Ј(forward primer) and 5Ј- The main complaint for 13 patients was easily pluck- GGAGACAAACTTGACGCTAGAACCA-3Ј (reverse able hair. The number of haircuts ranged from none from primer) for amplification of the 2B region. Polymer- birth to 1 every 2 months. Nine patients had thin, lus- ase chain reaction analysis was performed (Expand terless, and/or dry hair. Unmanageable hair was noted Long Template PCR System; Roche, Mannheim, in 4 patients; hair was described as being rough, messed Germany). The polymerase chain reaction condi- up, or hard to comb. It was more evident in the occipital tions consisted of incubation for 2 minutes at 94°C, region in 2 patients. Last, when noted, hair length was followed by 30 cycles for 10 seconds at 94°C, 30 sec- reported as short or variable. It did not exceed 20 cm. onds at 60°C, and 2 minutes at 68°C. Polymerase chain All children were in good health. Eyebrows and eye- reaction products were separated by agarose gel elec- trophoresis, purified using silica gel beads (Roche), and lashes were normal. Nails were normal, except for one sequenced directly according to a radiolabeled chain patient who had fragile nails. One patient had hypodon- terminator cycle-sequencing protocol (Thermo Se- tia, and lacked incisors and premolars (Table). quenase; Amersham Biosciences, Braunschweig, Ger- A trichogram was obtained in 16 patients accord- many) by using the gene-specific primers as sequenc- ing to a routine technique of sampling hairs in 3 sites ing primers. (frontal, temporal, and occipital). Examination by light microscopy revealed a prevalence of dystrophic anagen hairs, and a low count of telogen hairs for 14 of the 16 patients (Table). These dystrophic anagen hairs were de- void of root sheaths, had a distorted bulb, and had a ta- age of the hair in the follicle. Unfortunately, the keratins pered end (Figure 1). For the 2 other patients, results expressed in the different layers of the IRS are not known. showed mostly normal anagen hairs. Nevertheless, dys- In contrast, the keratins expressed in the CL are known. trophic anagen hairs were still numerous (37.3% and The major keratin is the recently discovered type II cy- 19.3%, respectively) and clinical examination and pull tokeratin K6hf, which is exclusively expressed in the CL.6 test results were positive for LAHS. The other cytokeratins of the CL are keratin pairs, K6a/ The family history was positive for LAHS in 5 pa- K16 and K6b/K17.7 These keratin pairs are also ex- tients. Three of them had 1 adult relative (1 mother, 1 pressed in the outer root sheath and, therefore, muta- father, or 1 paternal aunt) who displayed clinical signs (REPRINTED) ARCH DERMATOL / VOL 138, APR 2002 WWW.ARCHDERMATOL.COM 502 ©2002 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 09/25/2021 A B Figure 1. A, A typical trichogram showing almost only dystrophic anagen hairs. B, Detail showing ruffled cuticles and distorted bulbs. of LAHS. The 2 other patients with a positive family his- I tory of LAHS (1 brother for one; a father, a brother, and 1 2 a sister for the other one, corresponding to family 7 de- Family 2 tailed in Figure 2) displayed, among normal or loose II anagen hairs, a special type of curly hairs.
Load more

Recommended publications
  • Prevalence and Incidence of Rare Diseases: Bibliographic Data
    Number 1 | January 2019 Prevalence and incidence of rare diseases: Bibliographic data Prevalence, incidence or number of published cases listed by diseases (in alphabetical order) www.orpha.net www.orphadata.org If a range of national data is available, the average is Methodology calculated to estimate the worldwide or European prevalence or incidence. When a range of data sources is available, the most Orphanet carries out a systematic survey of literature in recent data source that meets a certain number of quality order to estimate the prevalence and incidence of rare criteria is favoured (registries, meta-analyses, diseases. This study aims to collect new data regarding population-based studies, large cohorts studies). point prevalence, birth prevalence and incidence, and to update already published data according to new For congenital diseases, the prevalence is estimated, so scientific studies or other available data. that: Prevalence = birth prevalence x (patient life This data is presented in the following reports published expectancy/general population life expectancy). biannually: When only incidence data is documented, the prevalence is estimated when possible, so that : • Prevalence, incidence or number of published cases listed by diseases (in alphabetical order); Prevalence = incidence x disease mean duration. • Diseases listed by decreasing prevalence, incidence When neither prevalence nor incidence data is available, or number of published cases; which is the case for very rare diseases, the number of cases or families documented in the medical literature is Data collection provided. A number of different sources are used : Limitations of the study • Registries (RARECARE, EUROCAT, etc) ; The prevalence and incidence data presented in this report are only estimations and cannot be considered to • National/international health institutes and agencies be absolutely correct.
    [Show full text]
  • Hair Loss in Infancy
    SCIENCE CITATIONINDEXINDEXED MEDICUS INDEX BY (MEDLINE) EXPANDED (ISI) OFFICIAL JOURNAL OF THE SOCIETÀ ITALIANA DI DERMATOLOGIA MEDICA, CHIRURGICA, ESTETICA E DELLE MALATTIE SESSUALMENTE TRASMESSE (SIDeMaST) VOLUME 149 - No. 1 - FEBRUARY 2014 Anno: 2014 Lavoro: 4731-MD Mese: Febraury titolo breve: Hair loss in infancy Volume: 149 primo autore: MORENO-ROMERO No: 1 pagine: 55-78 Rivista: GIORNALE ITALIANO DI DERMATOLOGIA E VENEREOLOGIA Cod Rivista: G ITAL DERMATOL VENEREOL G ITAL DERMATOL VENEREOL 2014;149:55-78 Hair loss in infancy J. A. MORENO-ROMERO 1, R. GRIMALT 2 Hair diseases represent a signifcant portion of cases seen 1Department of Dermatology by pediatric dermatologists although hair has always been Hospital General de Catalunya, Barcelona, Spain a secondary aspect in pediatricians and dermatologists 2Universitat de Barcelona training, on the erroneous basis that there is not much in- Universitat Internacional de Catalunya, Barcelona, Spain formation extractable from it. Dermatologists are in the enviable situation of being able to study many disorders with simple diagnostic techniques. The hair is easily ac- cessible to examination but, paradoxically, this approach is often disregarded by non-dermatologist. This paper has Embryology and normal hair development been written on the purpose of trying to serve in the diag- nostic process of daily practice, and trying to help, for ex- ample, to distinguish between certain acquired and some The full complement of hair follicles is present genetically determined hair diseases. We will focus on all at birth and no new hair follicles develop thereafter. the data that can be obtained from our patients’ hair and Each follicle is capable of producing three different try to help on using the messages given by hair for each types of hair: lanugo, vellus and terminal.
    [Show full text]
  • R‑Spondin Family Members As Novel Biomarkers and Prognostic Factors in Lung Cancer
    4008 ONCOLOGY LETTERS 18: 4008-4015, 2019 R‑spondin family members as novel biomarkers and prognostic factors in lung cancer LINGZHI WU1*, WEILI ZHANG2*, JINXIAN QIAN3, JIAN WU3, LIYANG JIANG3 and CHUNHUA LING4 1Department of Oncology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006; 2Department of Gastroenterology, Xiangcheng People's Hospital, Suzhou, Jiangsu 215131; 3Department of Intensive Care Unit, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou, Jiangsu 215008; 4Department of Respiratory Diseases, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006, P.R. China Received November 29, 2018; Accepted May 15, 2019 DOI: 10.3892/ol.2019.10778 Abstract. The R-spondin (RSPO) family of secreted proteins Introduction consists of four members that have critical roles in embryonic development and organogenesis. However, the expression Lung cancer is one of the most fatal types of cancer in developed patterns and the exact roles of the individual RSPO family countries, and remains the leading cause of cancer-associated members in tumorigenesis and progression of lung cancer are mortality (1), with a higher mortality rate than prostate, breast unknown, particularly in non-small cell lung cancer, which and colon cancer combined, and with >1 million deaths expected accounts for 85% of all lung cancer cases. In the present study, per year worldwide (2). Although treatments for lung cancer data from the ONCOMINE database was used to compare the have improved in recent years, including surgery, chemotherapy, RNA expression levels of RSPOs in multiple different types radiation therapy, local treatment and targeted therapy, >50% of of cancer with normal controls.
    [Show full text]
  • Uncombable Hair Syndrome
    Uncombable hair syndrome Author: Professor Ralph Trüeb1 Creation date: September 2003 Scientific editor: Professor Antonella Tosti 1 Leitender Arzt, Dermatologische Klinik, UniversitätsSpital Zürich, Gloriastrasse 31, 8091 Zürich, Switzerland. [email protected] Abstract Disease name and synonyms Definition Differential diagnosis Frequency Clinical description Management including treatment Etiology Diagnostic methods Genetic counseling Unresolved questions References Abstract Uncombable hair syndrome is a rare structural anomaly of the hair shaft with variable penetrance (MIM 191480). It may become first apparent from 3 months to 12 years of age. The hair is normal in quantity and is usually silvery-blond or straw-colored. It is disorderly, it stands out from the scalp, and cannot be combed flat. The underlying structural anomaly is longitudinal grooving of the hair shaft, which appears triangular or kidney-shaped in cross section. Affected individuals often have a negative family history, though the characteristic hair shaft anomaly can be demonstrated in asymptomatic family members by scanning electron microscopy. To be clinically apparent, 50 % of hairs must be affected by the structural abnormality. Spontaneous improvement often occurs in later childhood. Pili canaliculi have also been described associated with features of ectodermal dysplasia, and are a constant, though less pronounced finding, in the loose anagen hair syndrome. Autosomal-dominant inheritance is likely. The stiffness of the uncombable hair has been explained by the triangular form of the hair shaft in cross section. It has been suggested that the condition may result from premature keratinization of the inner root sheath. Diagnosis is suspected at clinical examination and confirmed through visualization of the hair shaft anomaly.
    [Show full text]
  • What Is Your Diagnosis?
    PHOTO QUIZ What Is Your Diagnosis? IMAGE NOT IMAGE NOT AVAILABLE ONLINE AVAILABLE ONLINE A 4-year-old girl presented to the dermatology clinic for the treatment of bullous impetigo. Examination revealed resolving angular cheilitis with secondary impetiginization, as well as frizzy, blond, unkempt-appearing shoulder-length hair. The patient’s parents reported that the girl’s hair was difficult to comb and had been unmanageable since birth. The patient is the offspring of nonconsanguineous parents and was the product of a healthy pregnancy. She was born at 38 weeks’ gestation by uncomplicated vaginal delivery and had experienced healthy growth and development. There was no known family history of hair disease. PLEASE TURN TO PAGE 31 FOR DISCUSSION Heidi F. Anderson, MD, University of Virginia School of Medicine, Charlottesville. Cheryl L. Lonergan, MD, Department of Dermatology, University of Virginia. Hina S. Qureshi, MD, Department of Pathology, University of Virginia. Kelly M. Cordoro, MD, Department of Dermatology, University of Virginia. The authors report no conflict of interest. 20 CUTIS® Photo Quiz Discussion The Diagnosis: Uncombable Hair Syndrome irst described in 1973 by Dupre et al1 as cheveux incoiffables and also now known as spun glass F hair and pili trianguli et canaliculi, uncomb- able hair syndrome is characterized by dry, frizzy, silvery blond to light brown hair that does not lay flat on the head. Typically, the hair is noncompliant with attempts at management by a comb or brush.2 Uncombable hair syndrome presents in infancy or during adolescence in rare cases.3 Hair grows at a slow to average rate, and the syndrome is not associ- IMAGE NOT ated with any hair loss or fragility.4 Both inherited AVAILABLE ONLINE (autosomal dominant gene with incomplete pen- etrance) and sporadic forms have been described,5 though the genetic or biochemical changes underly- ing this condition have yet to be determined.6 The exact prevalence of uncombable hair syndrome is unknown.
    [Show full text]
  • Table I. Genodermatoses with Known Gene Defects 92 Pulkkinen
    92 Pulkkinen, Ringpfeil, and Uitto JAM ACAD DERMATOL JULY 2002 Table I. Genodermatoses with known gene defects Reference Disease Mutated gene* Affected protein/function No.† Epidermal fragility disorders DEB COL7A1 Type VII collagen 6 Junctional EB LAMA3, LAMB3, ␣3, ␤3, and ␥2 chains of laminin 5, 6 LAMC2, COL17A1 type XVII collagen EB with pyloric atresia ITGA6, ITGB4 ␣6␤4 Integrin 6 EB with muscular dystrophy PLEC1 Plectin 6 EB simplex KRT5, KRT14 Keratins 5 and 14 46 Ectodermal dysplasia with skin fragility PKP1 Plakophilin 1 47 Hailey-Hailey disease ATP2C1 ATP-dependent calcium transporter 13 Keratinization disorders Epidermolytic hyperkeratosis KRT1, KRT10 Keratins 1 and 10 46 Ichthyosis hystrix KRT1 Keratin 1 48 Epidermolytic PPK KRT9 Keratin 9 46 Nonepidermolytic PPK KRT1, KRT16 Keratins 1 and 16 46 Ichthyosis bullosa of Siemens KRT2e Keratin 2e 46 Pachyonychia congenita, types 1 and 2 KRT6a, KRT6b, KRT16, Keratins 6a, 6b, 16, and 17 46 KRT17 White sponge naevus KRT4, KRT13 Keratins 4 and 13 46 X-linked recessive ichthyosis STS Steroid sulfatase 49 Lamellar ichthyosis TGM1 Transglutaminase 1 50 Mutilating keratoderma with ichthyosis LOR Loricrin 10 Vohwinkel’s syndrome GJB2 Connexin 26 12 PPK with deafness GJB2 Connexin 26 12 Erythrokeratodermia variabilis GJB3, GJB4 Connexins 31 and 30.3 12 Darier disease ATP2A2 ATP-dependent calcium 14 transporter Striate PPK DSP, DSG1 Desmoplakin, desmoglein 1 51, 52 Conradi-Hu¨nermann-Happle syndrome EBP Delta 8-delta 7 sterol isomerase 53 (emopamil binding protein) Mal de Meleda ARS SLURP-1
    [Show full text]
  • The Genetics of Hair Shaft Disorders
    CONTINUING MEDICAL EDUCATION The genetics of hair shaft disorders AmyS.Cheng,MD,a and Susan J. Bayliss, MDb,c Saint Louis, Missouri Many of the genes causing hair shaft defects have recently been elucidated. This continuing medical education article discusses the major types of hair shaft defects and associated syndromes and includes a review of histologic features, diagnostic modalities, and findings in the field of genetics, biochemistry, and molecular biology. Although genetic hair shaft abnormalities are uncommon in general dermatology practice, new information about genetic causes has allowed for a better understanding of the underlying pathophysiologies. ( J Am Acad Dermatol 2008;59:1-22.) Learning objective: At the conclusion of this article, the reader should be familiar with the clinical presentation and histologic characteristics of hair shaft defects and associated genetic diseases. The reader should be able to recognize disorders with hair shaft abnormalities, conduct appropriate referrals and order appropriate tests in disease evaluation, and select the best treatment or supportive care for patients with hair shaft defects. EVALUATION OF THE HAIR progresses via interactions with the mesenchymal For the student of hair abnormalities, a full review dermal papillae, leading to the formation of anagen of microscopic findings and basic anatomy can be hairs with complete follicular components, including found in the textbook Disorders of Hair Growth by sebaceous and apocrine glands.3 Elise Olsen,1 especially the chapter on ‘‘Hair Shaft Anagen hair. The hair shaft is composed of three Disorders’’ by David Whiting, which offers a thor- layers, called the medulla, cortex, and cuticle (Fig 1). ough review of the subject.1 The recognition of the The medulla lies in the center of the shaft and anatomic characteristics of normal hair and the effects contains granules with citrulline, an amino acid, of environmental factors are important when evalu- which is unique to the medulla and internal root ating a patient for hair abnormalities.
    [Show full text]
  • Prevalence and Incidence of Rare Diseases
    Number 2 | January 2019 Prevalence and incidence of rare diseases: Bibliographic data Diseases listed by decreasing prevalence, incidence or number of published cases www.orpha.net www.orphadata.org prevalence or incidence. Methodology When a range of data sources is available, the most recent data source that meets a certain number of quality criteria Orphanet carries out a systematic survey of literature in is favoured (registries, meta-analyses, population-based order to estimate the prevalence and incidence of rare studies, large cohorts studies). diseases. This study aims to collect new data regarding point prevalence, birth prevalence and incidence, and to For congenital diseases, the prevalence is estimated, so update already published data according to new scientific that: studies or other available data. Prevalence = birth prevalence x (patient life expectancy/general population life expectancy). This data is presented in the following reports published biannually: When only incidence data is documented, the prevalence • Prevalence, incidence or number of published cases is estimated when possible, so that : listed by diseases (in alphabetical order) ; • Diseases listed by decreasing prevalence, incidence or Prevalence = incidence x disease mean duration. number of published cases ; When neither prevalence nor incidence data is available, Data collection which is the case for very rare diseases, the number of cases or families documented in the medical literature is A number of different sources are used : provided. Limitations of the study Registries (RARECARE, EUROCAT, etc) ; The prevalence and incidence data presented in this report National/international health institutes and agencies are only estimations and cannot be considered to be (Institut National de Veille Sanitaire (French Institute absolutely correct.
    [Show full text]
  • PADI3 Induces Cell Cycle Arrest Via the Sirt2/AKT/P21 Pathway and Acts As a Tumor Suppressor Gene in Colon Cancer
    Cancer Biol Med 2019. doi: 10.20892/j.issn.2095-3941.2019.0065 ORIGINAL ARTICLE PADI3 induces cell cycle arrest via the Sirt2/AKT/p21 pathway and acts as a tumor suppressor gene in colon cancer Xiaotian Chang1,2, Zhengbin Chai3, Jiaorui Zou1, Hongxing Wang1, Yao Wang1, Yabing Zheng1, Hui Wu1, Chunyan Liu1 1Medical Research Center, The First Affiliated Hospital of Shandong First Medical University, Jinan 250014, China; 2Medical Research Center of the Hospital Affiliated to Qingdao University, Qingdao 266000, China; 3Department of Laboratory Medicine, Jinan Infectious Disease Hospital, Shandong University, Jinan 250021, China ABSTRACT Objective: As a member of the peptidyl arginine deiminase (PAD) family, PADI3 is weakly expressed in colon cancer tissues and highly expressed in adjacent colon cancer tissues. However, the role of PADI3 in colon cancer is unclear. In this study, we investigated the function and molecular mechanism of PADI3 in colon cancer tumorigenesis. Methods: Western blot and real-time PCR were used to detect the expression levels of several genes. CCK-8, flow cytometry (FCM) and colony formation assays were used to examine cell proliferation, the cell cycle and colony formation ability. RNA- sequencing analysis was used to study the molecular mechanism of PADI3 in tumorigenesis. A truncation mutation experiment was performed to determine the key functional domain of PADI3. Results: PADI3 overexpression inhibited cell proliferation and colony formation and led to G1 phase arrest in both HCT116 (originating from primary colon cancer) and LoVo (originating from metastatic tumor nodules of colon cancer) cells. PADI3- expressing HCT116 cells had a lower tumor formation rate and produced smaller tumors than control cells.
    [Show full text]
  • Updates in Our Understanding of Central Centrifugal Cicatricial Alopecia
    GUEST EDITORIAL Updates in Our Understanding of Central Centrifugal Cicatricial Alopecia Crystal Aguh, MD t has been more than 50 years since central centrifugal other fibroproliferative disorders, in affected scalp of cicatricial alopecia (CCCA) was first defined by LoPresti patients with CCCA.7 Most notably, an expression in gene Iand colleagues1 as hot comb alopecia. Fifty years later, we overlap was noted between fibroids and CCCA in this are only just starting to understand the pathogenesis of study, though the relationship between these two diseases CCCA and its systemic implications. needs to be further explored. Then and Now Gene Variants Identified in CCCA The use of hot combs, a metal device used to straighten More recently, a copynew study has identified a gene variant naturally curly hair, was ubiquitous in the households of of peptidyl arginine deiminase 3, PADI3, that is present black women in the 1960s. It is no surprise then that this in approximately one-quarter of studied patients with styling process was labeled as the culprit of this disease CCCA.8 PADI3 plays a role in hair shaft formation and has that affects black women almost exclusively. As the use of been implicated in another hair disorder, uncombable hair hot combs waned but the prevalence of CCCA persisted, syndrome,not though the latter presents in children, improves its name evolved to chemically induced alopecia—an ode with age, and is not associated with a scarring phenotype.9 to the popular styling product of the 1990s, the chemical However, this study
    [Show full text]
  • Genetic Susceptibility to Alopecia
    Thomas Jefferson University Jefferson Digital Commons Department of Dermatology and Cutaneous Department of Dermatology and Cutaneous Biology Faculty Papers Biology 2-28-2019 Genetic Susceptibility to Alopecia. Jouni Uitto Thomas Jefferson University Follow this and additional works at: https://jdc.jefferson.edu/dcbfp Part of the Dermatology Commons Let us know how access to this document benefits ouy Recommended Citation Uitto, Jouni, "Genetic Susceptibility to Alopecia." (2019). Department of Dermatology and Cutaneous Biology Faculty Papers. Paper 111. https://jdc.jefferson.edu/dcbfp/111 This Article is brought to you for free and open access by the Jefferson Digital Commons. The Jefferson Digital Commons is a service of Thomas Jefferson University's Center for Teaching and Learning (CTL). The Commons is a showcase for Jefferson books and journals, peer-reviewed scholarly publications, unique historical collections from the University archives, and teaching tools. The Jefferson Digital Commons allows researchers and interested readers anywhere in the world to learn about and keep up to date with Jefferson scholarship. This article has been accepted for inclusion in Department of Dermatology and Cutaneous Biology Faculty Papers by an authorized administrator of the Jefferson Digital Commons. For more information, please contact: [email protected]. Editorials tomy for advanced ovarian cancer — therapeutic advance or sur- 6. Rungruang BJ, Miller A, Krivak TC, et al. What is the role of gical folly? Gynecol Oncol 1995; 56: 325-7. retroperitoneal exploration in optimally debulked stage IIIC 3. Aletti GD, Dowdy S, Podratz KC, Cliby WA. Role of lymphad- epithelial ovarian cancer? An NRG Oncology/Gynecologic On- enectomy in the management of grossly apparent advanced cology Group ancillary data study.
    [Show full text]
  • Hair Shaft Defects
    Hair Sha( Defects Clinical presentation is variable Childhood or adulthood Inherited or acquired Patchy or diffuse alopecia Isolated or associated anomalies Hair Sha( Defects Increased fragility Normal Strength Monilethrix Pili Annulati Pili torti Wooly Hair Menkes’ Kinky Hair Straight Hair Nevus Netherton’s Progressive Kinking Trichorrhexis Nodosa Uncombable Hair Trichothiodystrophy Loose Anagen Hair Sha( Defects Terminology “tricho”: pertaining to hair “pilo”: pertaining to hair “thio”: prefix denoting sulfur “monil”: necklace Suffix “schisis”: cleavage Suffix “ptilosis”: feather Suffix “clasis”: break off Increased Fragility Monilethrix Genetics Autosomal dominant Mutation in Hhb1 and Hhb6 Clinical In childhood w/patchy alopecia and dry, lusterless hair Follicular keratosis at nape of neck; KP common Stable, but may improve at puberty Pathology “beads” every 0.7-1mm apart No medulla at internodes Associated defects: rare case reports (cataracts, oligophrenia) Monilethrix Nodes are at regular intervals 0.7-1mm apart Non-medullated Normal caliber, medullated Monilethrix Lusterless, brittle hair. Patchy alopecia due to breakage. Increased Fragility Pili Torti Genetics Autosomal dominant Clinical Childhood; hair won’t grow beyond a few inches Pathology “Twisted look”: hairs are flattened, and rotated 180 at irregular intervals Associated defects: Menkes’, Bjornstad’s, ectodermal dysplasia Pili Torti Increased Fragility Pili Torti (cont) Menkes Kinky Hair Genetics X-linked recessive (males only)
    [Show full text]