Autosomal Recessive Ichthyosis Research Articles

SDR9C7 missense variant in a Chihuahua with non-epidermolytic ichthyosis.

Ichthyoses represent a heterogeneous group of cornification disorders that are associated with skin barrier defects. We investigated a 9-month-old Chihuahua showing excessive scale formation. Clinical and histopathological examinations revealed non-epidermolytic ichthyosis and a genetic defect was suspected. We therefore sequenced the genome of the affected dog and compared the data with 564 genetically diverse control genomes. Filtering for private variants identified a homozygous missense variant in SDR9C7, c.454C>T or p.(Arg152Trp). SDR9C7 is a known candidate gene for ichthyosis in humans and encodes the short-chain dehydrogenase/reductase family 9C member 7. The enzyme is involved in the production of a functional corneocyte lipid envelope (CLE), a crucial component of the epidermal barrier. Pathogenic variants in SDR9C7 have been described in human patients with autosomal recessive ichthyosis. We assume that the identified missense variant in the affected Chihuahua of this study impairs the normal enzymatic activity of SDR9C7 and thus prevents the formation of a functioning CLE, resulting in a defective skin barrier. To the best of our knowledge, this is the first report of a spontaneous SDR9C7 variant in domestic animals.

PRSS8, encoding prostasin, is mutated in patients with autosomal recessive ichthyosis.

Ichthyosis is a genetically heterogeneous genodermatosis characterized by severely rough, dry and scaly skin. We report two consanguineous families with congenital ichthyosis. Combined positional mapping and exome sequencing of the two families revealed novel homozygous likely deleterious variants in PRSS8 (encoding prostasin) within a linkage locus on chromosome 16. One variant involved a canonical splice site and was associated with reduced abundance of the normal transcript, while the other was a missense variant that altered a highly conserved residue. The phenotype of Prss8 knockout mouse bears a striking resemblance to the one we describe in human patients, including the skin histopathology. Our data suggest a novel PRSS8-related ichthyosis disorder.

ABHD5 frameshift deletion in Golden Retrievers with ichthyosis.

Ichthyoses are hereditary skin disorders characterized by the formation of scales and defects in the outermost layer of the epidermis. In dogs, at least six different breed-specific ichthyoses including a relatively common PNPLA1-related autosomal recessive ichthyosis in Golden Retrievers are known. In this study, we investigated 14 Golden Retrievers with scales that were not homozygous for the mutant PNPLA1 allele suggesting a genetically distinct new form of ichthyosis. Histopathological examinations showed lamellar, orthokeratotic hyperkeratosis, and mildly hyperplastic epidermis that led to the diagnosis of a nonepidermolytic ichthyosis. Combined linkage and homozygosity mapping in 14 cases and 30 nonaffected family members delimited a critical interval of ∼12.7 Mb on chromosome 23. Whole-genome sequencing of an affected dog revealed a single protein-changing variant within this region that was not present in 795 control genomes. The identified variant is a 14 bp deletion in the ABHD5 gene (c.1006_1019del), leading to a frameshift and altering the last 14 codons p.(Asp336Serfs*6). The genotypes at this variant showed perfect cosegregation with the ichthyosis phenotype in a large family comprising 14 cases and 72 controls. ABHD5 encodes an acyltransferase required for lipid metabolism. In humans, variants in ABHD5 cause Chanarin-Dorfman syndrome, a neutral lipid storage disease with ichthyosis. Our data in dogs together with the knowledge on the effects of ABHD5 variants in humans strongly suggest ABHD5:c.1006_1019del as candidate causative genetic variant for a new canine form of ichthyosis, which we propose to designate as Golden Retriever ichthyosis type 2 (ICH2).

Essential Functions of Glycans in Human Epithelia Dissected by a CRISPR-Cas9-Engineered Human Organotypic Skin Model.

SummaryThe glycome undergoes characteristic changes during histogenesis and organogenesis, but our understanding of the importance of select glycan structures for tissue formation and homeostasis is incomplete. Here, we present a human organotypic platform that allows genetic dissection of cellular glycosylation capacities and systematic interrogation of the roles of distinct glycan types in tissue formation. We used CRISPR-Cas9 gene targeting to generate a library of 3D organotypic skin tissues that selectively differ in their capacity to produce glycan structures on the main types of N- and O-linked glycoproteins and glycolipids. This tissue library revealed distinct changes in skin formation associated with a loss of features for all tested glycoconjugates. The organotypic skin model provides phenotypic cues for the distinct functions of glycoconjugates and serves as a unique resource for further genetic dissection and identification of the specific structural features involved. The strategy is also applicable to other organotypic tissue models.

Duality of Netherton syndrome manifestations and response to ixekizumab

To the Editor: Netherton syndrome (NS) is a rare autosomal recessive ichthyosis due to loss-of-function mutations in SPINK5 encoding LEKTI.1 Patients with NS typically present with ichthyosis linearis circumflexa (NS-ILC) or scaly erythroderma (NS-SE) associated with trichorrhexis invaginata and severe atopic manifestations with high serum immunoglobulin E levels.2 Current NS treatment is only symptomatic. Recent studies showed that patients with NS display a prevailing T helper (Th) type 17 immune response,3,4 suggesting that blocking the Th17 axis could be a therapeutic strategy.

Juvenile idiopathic arthritis in infants with Harlequin Ichthyosis: two cases report and literature review

BackgroundHarlequin Ichthyosis is the most severe variant of congenital autosomal recessive ichthyosis, associated with severe morbidity and potentially lethal in early life. At birth, patients present thick and plaque-like scales all over the body, with consequent cutaneous and extra-cutaneous complications, such as poor thermoregulation, recurrent infections, pain, electrolytes imbalance and joint contractures. Juvenile Idiopathic Arthritis usually manifests before the age of 16 years and persists for more than 6 weeks. The association between these two pathologies has been described in the literature as a very rare event, which creates diagnostic and therapeutic challenge.Case presentationWe describe two patients affected by Harlequin Ichthyosis who early developed Juvenile Idiopathic Arthritis. Both patients were treated with retinoids, ibuprofen and long-acting intra-articular glucocorticoids; due to polyarticular involvement, one child was also treated with weekly oral methotrexate.ConclusionsThe association between Harlequin Ichthyosis and Juvenile Idiopathic Arthritis is rare and the pathophysiological mechanism that binds them is still unknown. Nonetheless caregivers should be aware of the possible occurrence of Juvenile Idiopathic Arthritis at very early ages in children affected by Harlequin Ichthyosis.

A study of gene mutations and how they relate to the different types of ichthyosis

Ichthyosis is a disorder in which the skin is very thick and scaly. It is usually caused by a genetic mistake (mutation). “Autosomal recessive” ichthyosis occurs when parents who are healthy carriers both pass on a mutant gene to their child, so the child inherits a double dose of the mutation and cannot make normal skin. Scientists have already discovered mutations in 13 genes that cause ichthyosis. This study looks at whether the type of mutation (genotype) tells us anything about the type of ichthyosis (phenotype). The doctors examined 146 ichthyosis patients, average age 17 years, from 124 families, recruited from 13 English hospitals. They extracted DNA from blood or saliva. They found mutations in 83% of patients; the other 17% presumably have mutations not detectable by current techniques or in different genes. There were mutations in 10 different ichthyosis genes, mostly a gene called TGM1. To some extent different genotypes corresponded to different phenotypes. TGM1 ichthyosis usually has large, brown scales while ALOX12B mutations cause fine white scaling. ABCA12 mutations cause more severe ichthyosis, including the very serious harlequin type with distorted fingers; by contrast patients with milder ichthyosis usually had TGM1 or ALOX12B mutations. Nearly half of the babies with ALOX12B mutations were born with the top of their ear folded over. Some TGM1 patients had abnormally red skin while others with exactly the same mutation did not. In conclusion, this large study provides a lot of new information about ichthyosis, but genotype only partly predicts phenotype. This is a summary of the study: Genotype–phenotype correlation in a large English cohort of patients with autosomal recessive ichthyosis

Genotype-phenotype correlation in a large English cohort of patients with autosomal recessive ichthyosis.

Recessive forms of congenital ichthyosis encompass a group of rare inherited disorders of keratinization leading to dry, scaly skin. So far, 13 genes have been implicated, but there is a paucity of data on genotype-phenotype correlation in some populations. We compiled an English cohort of 146 individuals with recessive ichthyosis and assessed genotype-phenotype correlation. Deep phenotyping was undertaken by history-taking and clinical examination. DNA was screened for mutations using a next-generation sequencing ichthyosis gene panel and Sanger sequencing. Cases were recruited from 13 National Health Service sites in England, with 65% of patients aged < 16 years at enrolment. Pathogenic biallelic mutations were found in 83% of cases, with the candidate gene spread as follows: TGM1 29%, NIPAL4 12%, ABCA12 12%, ALOX12B 9%, ALOXE3 7%, SLC27A4 5%, CERS3 3%, CYP4F22 3%, PNPLA1 2%, SDR9C7 1%. Clinically, a new sign, an anteriorly overfolded ear at birth, was noted in 43% of patients with ALOX12B mutations. The need for intensive care stay (P = 0·004), and hand deformities (P < 0·001), were associated with ABCA12 mutations. Self-improving collodion ichthyosis occurred in 8% of the cases (mostly TGM1 and ALOX12B mutations) but could not be predicted precisely from neonatal phenotype or genotype. These data refine genotype-phenotype correlation for recessive forms of ichthyosis in England, demonstrating the spectrum of disease features and comorbidities, as well as the gene pathologies therein. Collectively, the data from these patients provide a valuable resource for further clinical assessment, improving clinical care and the possibility of future stratified management. What's already known about this topic? Recessive forms of ichthyosis are rare but often difficult to diagnose. Mutations in 13 genes are known to cause recessive forms of ichthyosis: ABCA12, ALOX12B, ALOXE3, CERS3, CYP4F22, LIPN, NIPAL4, PNPLA1, SDR9C7, SLC27A4, SULT2B1, ST14 and TGM1. Some phenotypic features may associate with certain gene mutations, but paradigms for genotype-phenotype correlation need refining. What does this study add? The genotypic spectrum of recessive ichthyosis in England (based on 146 cases) comprises TGM1 (29%), NIPAL4 (12%), ABCA12 (12%), ALOX12B (9%), ALOXE3 (7%), SLC27A4 (5%), CERS3 (3%), CYP4F22 (3%), PNPLA1 (2%) and SDR9C7 (1%). New or particular phenotypic clues were defined for mutations in ALOX12B, ABCA12, CYP4F22, NIPAL4, SDR9C7 and TGM1, either in neonates or in later life, which allow for greater diagnostic precision. In around 17% of cases, the molecular basis of recessive ichthyosis remains unknown.

Co-Occurrence of Autosomal Recessive Lamellar Ichthyosis and X-Linked Recessive Ichthyosis in a Consanguineous Pakistani Family.

Co-Occurrence of Autosomal Recessive Lamellar Ichthyosis and X-Linked Recessive Ichthyosis in a Consanguineous Pakistani Family.

Lamellar Icthyosis: A Clinical Dilemma

Congenital Autosomal recessive ichthyosis is a heterogenous group of disorders that are present at birth with generalized involvement of skin and lack of other organ systems. This case report presents involvement of respiratory system and its management with outcome in a rather uncommon presentation of lamellar icthyosis.

A disease-causing novel missense mutation in the ST14 gene underlies autosomal recessive ichthyosis with hypotrichosis syndrome in a consanguineous family.

Autosomal recessive ichthyosis with hypotrichosis (ARIH; MIM 602400) syndrome is characterized by diffused congenital ichthyosis and generalized non-scarring hypotrichosis. The underlying genetic cause of ARIH syndrome has been associated with sequence variants of the gene ST14, encoding type II transmembrane serine protease matriptase, which maps to chromosome 11q24.3. The current report aimed to investigate the clinical features and genetic cause of ARIH syndrome in a large consanguineous family of Pakistani origin. The technique of homozygosity mapping with highly polymorphic microsatellite markers was employed to establish linkage within the family. Sanger sequencing of exons and intron-exon boundaries of ST14 was performed to identify the potential pathogenic sequence variants, followed by structural analysis of the mutated protein. Linkage was established to chromosome 11q24.3, comprising the gene ST14. Sequence analysis led to the identification of a novel homozygous missense variant (c.1315G>A, p.Gly439Ser) in the ST14 gene that co-segregated with the disease phenotype in all affected members. Homology modelling and molecular docking analysis of ST14 with wild-type TMEFF1 protein was performed which revealed that glycine at position 439 is crucial for maintaining normal structural confirmation and interaction with the EGF domain of TMEFF1 protein. Taken together, the data strongly advocate this ST14 variant as the underlying genetic cause of ARIH syndrome in this first reported affected family from Pakistan. Moreover, the present study adds to the spectrum of mutations in the ST14 gene, implicating them in the pathogenesis of ARIH syndrome.

Transglutaminases in autoimmune and inherited skin diseases: The phenomena of epitope spreading and functional compensation.

Transglutaminases (TGs) are structurally and functionally related enzymes that modify the post-translational structure and activity of proteins or peptides, and thus are able to turn on or switch off their function. Depending on location and activities, TGs are able to modify the signalling, the function and the fate of cells and extracellular connective tissues. Besides mouse models, human diseases enable us to appreciate the function of various TGs. In this study, skin diseases induced by genetic damages or autoimmune targeting of these enzymes will be discussed. TG1, TG3 and TG5 contribute to the cutaneous barrier and thus to the integrity and function of epidermis. TGM1 mutations related to autosomal recessive ichthyosis subtypes, TGM5 mutations to a mild epidermolysis bullosa phenotype and as novelty TGM3 mutation to uncombable hair syndrome will be discussed. Autoimmunity to TG2, TG3 and TG6 may develop in a few of those genetically determined individuals who lost tolerance to gluten, and manifest as coeliac disease, dermatitis herpetiformis or gluten-dependent neurological symptoms, respectively. These gluten responder diseases commonly occur in combination. In autoimmune diseases, the epitope spreading is remarkable, while in some inherited pathologies, a unique compensation of the lost enzyme function is noted.

102 Proteins causing autosomal congenital recessive ichthyosis (ARCI) colocalize in differentiated primary keratinocytes and the interactions are altered in cells from patients with TGM1 mutations

Proteins causing autosomal congenital recessive ichthyosis (ARCI) colocalize in differentiated primary keratinocytes and the interactions are altered in cells from patients with TGM1 mutations

Colloidion Baby: A Rare Clinical Entity.

Colloidion baby is a rare clinical entity. Herein the neonate is born with a shiny, yellowish parchment like transparent membrane stretched over the skin. It was Hallopeau and Watelet in 1892, who first used this term and since then literature has a record of nearly 270 colloidian babies [1]. Eventually, these children will develop signs of one of the several types of ichthyosis, giving the skin ‘fish scales’ appearance [2]. We herein report one such case owing to its rarity. A primi gravida presented at 32 weeks of gestation according to her last menstrual period with complaint of leaking per vaginum for two days prior to presentation. There was no personal or family history of diabetes, any exposure to teratogenic drug, no history of any chronic medical disorders. Mother was diagnosed as pregnancy induced hypertension but was not on any treatment. Her present pregnancy was followed in a local hospital with regular follow-up with ultrasonography examination done one week prior to delivery showing oligohydramnios (decreased amniotic fluid index=4). There was no comment on any congenital malformations. On admission patient was haemodynamically stable. On abdominal examination, fundal height corresponded to 32 weeks of gestation with breech presentation with normal fetal heart rate pattern. On per vaginal examination cervix was closed and not effaced with high breech with clear dribbling liquid. She was started on intravenous antibiotics and betamethasone was given. Caessarean section was planned after 48 hours and a 1900 grams female baby was born with following morphological features [Table/Fig-1]. [Table/Fig-1]: Appearance of baby on day 1 of life. Thick shield like taut skin all over body with cracked pinkish areas in between, scanty hair, malformed ears, everted eyelids with exposed swollen conjunctiva, slit like nostril, open mouth, flexed limbs with malformed palms, oedematous feet were present. Baby did not need active resuscitation and was shifted to neonatal intensive care unit. Dermatological opinion was taken and a diagnosis of Harlequin ichthyosis was made. Baby was managed with intravenous fluids, intravenous antibiotics and topical emollients. Baby remained haemodynamically stable with cracks in the skin increasing [Table/Fig-2]. Baby was taken to home against medical advice on fifth day of life and lost to follow-up. [Table/Fig-2]: Appearance of baby on day 4 of life. Approximately 75% of collodion baby develops a type of autosomal recessive congenital ichthyosis, either lamellar ichthyosis or congenital ichthyosiform erythrodema) [3]. The third type of autosomal recessive congenital ichthyosis, Harlequin ichthyosis, is the most rare and severe form. Other rare causes of colloidion baby include-Epidermolytic hyperkeratosis (bullous congenital ichthyosiform erythroderma), Gaucher’s disease and Sjogren-Larsson syndrome. Although, the colloidian membrane develops due to an epidermal cornification disorder, keratinocyte protein and lipid metabolism defects resulting from autosomal recessive genetic mutations have also been notified as important cofactors [4]. Transglutaminase 1 gene mutation localized on the 14q11 have been implicated in congenital autosomal recessive ichthyosis [5]. Owing to impairment of the skin barrier function, collodion babies prone for a number of complications like hypernatremic dehydration, hypothermia, skin infections, fissures, conjunctivitis, sepsis, dehydration and constrictive bands of the extremities resulting in vascular compromise and oedema [1,2]. They require proper fluid and electrolyte balance, emollients and lubricants for hydrating the membrane. Suitable eye care and pain control should be carried out for the collodion babies with ectropion. Prophylactic antibiotics should be used to prevent sepsis. In the present scenario, owing to intensive care, the survival of neonates has increased. Humidified incubators and water dressings followed by emollient agents are important aspects in its management.

Novel ABCA12 mutations in harlequin ichthyosis: A journey from photo diagnosis to prenatal diagnosis

Harequin ichthyosis is a severe autosomal recessive ichthyosis of congenital onset caused by biallelic mutations in the ABCA12 gene. We report two neonates of Indian origin with harlequin ichthyosis. The parents were retrospectively found to have novel mutations in ABCA12 gene after neonatal demise, which helped in providing prenatal diagnosis in subsequent pregnancies.

Matriptase Regulates Proliferation and Early, but Not Terminal, Differentiation of Human Keratinocytes

Genetic defects in matriptase are linked to two congenital ichthyosis, autosomal recessive ichthyosis with hypotrichosis (ARIH, OMIM 610765) and, ichthyosis, follicular atrophoderma, hypotrichosis, and hypohidrosis (IFAH, OMIM602400). Mouse models with matriptase deficiency indicate an involvement of matriptase in suprabasal keratinocytes in the maintenance of the epidermal barrier. In contrast to what has been reported for mouse skin, we show that in human skin, matriptase is primarily expressed in the basal and spinous keratinocytes, but not in the more differentiated keratinocytes of the granular layer. In addition, matriptase zymogen activation was predominantly detected in the basal cells. Furthermore, using skin organotypic cultures as a model system to monitor the course of human epidermal differentiation, we found elevated matriptase zymogen activation during early stages of epidermal differentiation, coupled with a loss of matriptase expression in the late stages of this process. We also show here that matriptase deficiency in HaCaT cells modestly reduces cell proliferation and temporally affects calcium-induced expression of differentiation markers. These collective data suggests that, unlike mouse matriptase, human matriptase may be involved in regulation of keratinocyte growth and early differentiation, rather than terminal differentiation, providing mechanistic insights for the pathology of the two congenital ichthyoses, ARIH and IFAH.

Non-bullous Ichthyosiform Erythroderma with Mosaic Turner’s Syndrome - a Rare Association

The ichthyoses are a heterogenous group of skin diseases characterized by generalised scaling. Non-bullous Ichthyosiform Erythroderma (NBIE) or congenital ichthyosiform erythroderma is a rare and usually severe autosomal recessive inflammatory ichthyosis. Turner’s syndrome is a condition caused by numeric and structural abnormalities of the X chromosome. In individuals with mosaic Turner’s syndrome, the second X chromosome is not entirely missing. In addition to the expanding list of syndromes that combine with ichthyosis. We report non-bullous ichthyosiform erythroderma in a patient with mosaic Turner’s syndrome. To our knowledge no such association has been reported in literature to date.

Narrowband ultraviolet B phototherapy associated with improvement in Netherton syndrome

Netherton syndrome (NS) is a rare and severe autosomal recessive ichthyosis. We report the case of a patient with NS treated successfully with narrowband ultraviolet B (NB-UVB) phototherapy after failure of low-dose oral isotretinoin. A 16-year-old girl born to consanguineous parents presented with severe ichthyosis. On examination of her hair, she was found to have trichorrhexis invaginata. Genetic analysis revealed a SPINK5 mutation specific for NS. The patient's cousin had the same mutation. The patient developed Cushing syndrome after long-term application of topical steroids. She was treated with low-dose oral isotretinoin with no benefit. NB-UVB phototherapy was started, which resulted in marked improvement after 2 months. In conclusion, we report a case of NS with failure of low-dose oral isotretinoin, for which NB-UVB phototherapy, through its apoptosis-inducing and immunomodulatory effects, was effective. However, long-term use of UVB is limited by its potential side-effects.

Netherton syndrome in one Chinese adult with a novel mutation in the SPINK5 gene and immunohistochemical studies of LEKTI

Background:Netherton syndrome (NS) is a severe autosomal recessive ichthyosis. It is characterized by congenital ichthyosiform erythroderma, trichorrhexis invaginata, ichthyosis linearis circumflexa, atopic diathesis, and frequent bacterial infections. The disease is caused by mutations in the SPINK5 (serine protease inhibitor Kazal-type 5) gene, a new type of serine protease inhibitor involved in the regulation of skin barrier formation and immunity. We report one Chinese adult with NS. The patient had typical manifestation of NS except for trichorrhexis invaginata with an atopic diathesis and recurrent staphylococcal infections since birth.Aims:To evaluate the gene mutation and of its product activity of SPINK5 gene in confirmation of the diagnosis of one Chinese adult with NS.Materials and Methods:To screen mutations in the SPINK5 gene, 33 exons and flanking intron boundaries of SPINK5 were amplified with polymerase chain reaction (PCR) and used for direct sequencing. In addition, immunohistochemical staining of LEKTI (lymphoepithelial Kazal-type-related inhibitor) with specific antibody was used to confirm the diagnosis of NS. The results were compared with that of healthy individuals (twenty-five blood samples).Results:A G318A mutation was found at exon 5 of patient's SPINK5 gene which is a novel missense mutation. The PCR amplification products with mutation-specific primer were obtained only from the DNA of the patients and their mother, but not from their father and 25 healthy individuals. Immunohistochemical studies indicated there was no LEKTI expression in NS patient's skin and there was a strong LEKTI expression in the normal human skin.Conclusion:In this report, we describe heterozygous mutation in the SPINK5 gene and expression of LEKTI in one Chinese with NS. The results indicate that defective expression of LEKTI in the epidermis and mutations of SPINK5 gene are reliable for diagnostic feature of NS with atypical clinical symptoms.

Postnatal 2- and 3-Dimensional Sonography of the Skin and Nail in Congenital Autosomal Recessive Ichthyosis Correlated With Cutaneous Histologic Findings

Journal of Ultrasound in MedicineVolume 30, Issue 10 p. 1437-1439 Clinical Letters Postnatal 2- and 3-Dimensional Sonography of the Skin and Nail in Congenital Autosomal Recessive Ichthyosis Correlated With Cutaneous Histologic Findings Ximena Wortsman MD, Ximena Wortsman MD Department of Radiology, Clinica Servet, Faculty of Medicine, University of Chile, Santiago, Chile.Search for more papers by this authorLigia Aranibar MD, Ligia Aranibar MD Department of Dermatology, Santiago, Chile.Search for more papers by this authorClaudia Morales MD, Claudia Morales MD Department of Pathology, Dermopathology Section, Hospital Clinico, University of Chile, Santiago, Chile.Search for more papers by this author Ximena Wortsman MD, Ximena Wortsman MD Department of Radiology, Clinica Servet, Faculty of Medicine, University of Chile, Santiago, Chile.Search for more papers by this authorLigia Aranibar MD, Ligia Aranibar MD Department of Dermatology, Santiago, Chile.Search for more papers by this authorClaudia Morales MD, Claudia Morales MD Department of Pathology, Dermopathology Section, Hospital Clinico, University of Chile, Santiago, Chile.Search for more papers by this author First published: 01 October 2011 https://doi.org/10.7863/jum.2011.30.10.1437Citations: 9Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat Citing Literature Volume30, Issue10October 2011Pages 1437-1439 RelatedInformation