It mostly happens in the. Select Features of SOX2 Disorder: Frequency of Human Phenotype Ontology (HPO) Terms. Both cases with patient's quality of life are noted in developing country. You must talk to your provider if you take isotretinoin and thalidomide. Shima H, Ishii A, Wada Y, Kizawa J, Yokoi T, Azuma N, Matsubara Y, Suzuki E, Nakamura A, Narumi S, Fukami M. SOX2 nonsense mutation in a patient clinically diagnosed with non-syndromic hypogonadotropic hypogonadism. How are genetic conditions treated or managed? david millward security; swarovski habicht 10x40; east hanover police scanner; sample complaint car accident negligence. Chassaing N, Causse A, Vigouroux A, Delahaye A, Alessandri JL, Boespflug-Tanguy O, Boute-Benejean O, Dollfus H, Duban-Bedu B, Gilbert-Dussardier B, Giuliano F, Gonzales M, Holder-Espinasse M, Isidor B, Jacquemont ML, Lacombe D, Martin-Coignard D, Mathieu-Dramard M, Odent S, Picone O, Pinson L, Quelin C, Sigaudy S, Toutain A, Thauvin-Robinet C, Kaplan J, Calvas P. Molecular findings and clinical data in a cohort of 150 patients with anophthalmia/microphthalmia. GeneReviews staff have not independently verified the classification of variants. Ted has Sox2 anophthalmia syndrome, caused by an unbalanced translocation of Chromosomes 3 and 14 and a microdeletion of Chromosome 3. GeneReviews is not responsible for the information provided by other The Human Phenotype Ontology (HPO) enables use of precise, standardized, computationally accessible terms to describe phenotypic abnormalities. With the current widespread use of advanced molecular genetic testing, it is apparent that the clinical spectrum associated with SOX2 pathogenic variants includes anophthalmia and/or microphthalmia as well as phenotypes with minimal or absent ocular findings. You may hear some people say that anophthalmia and microphthalmia are examples of eye birth defects.. Molecular genetic testing approaches can include a combination of gene-targeted testing (single-gene testing, multigene panel, and chromosomal microarray analysis [CMA]) and comprehensive Epub 2008 Nov Sox2 is involved in crystallin regulation in murine [ 22] and avian models [ 23] and humans, and SOX2 mutations cause microphthalmia and cataracts [ 24, 25 ]. Community hearing services through early intervention or school district, MRI, assessment of vision, ophthalmologic eval, Every 3-6 mos during childhood w/MRI only if change in clinical status, e.g., sudden change in light-dark or color perception, Follow-up eval w/ophthalmo-plastic surgeon. Br J Ophthalmol. 10.1002/ajmg.a.32384. Seattle (WA): University of Washington, Seattle; 1993-2023. sox2 anophthalmia syndrome life expectancy Isgho Votre ducation notre priorit See a healthcare provider before you get pregnant and work together so you can be as healthy as possible before and during your pregnancy. use. Hum Mol Genet. Microphthalmia, anophthalmia, coloboma (MAC): for patients Other names for microphthalmia include small eye syndrome and microphthalmos. The absence of this protein disrupts the activity of genes that are essential for the development of the eyes and other parts of the body. Its important to have a healthcare team if you or your child has microphthalmia or anophthalmia. Takagi M, Narumi S, Asakura Y, Muroya K, Hasegawa Y, Adachi M, Hasegawa T. A novel mutation in SOX2 causes hypogonadotropic hypogonadism with mild ocular malformation. SOX2 anophthalmia syndrome - North Carolina State University Prevalence is approximately 1:250,000 (UK estimate) [Author, personal data], extrapolated from Shah et al [2011], with no population differences noted. SOX2 Disorder - GeneReviews - NCBI Bookshelf old fashion trends that died . SOX2 anophthalmia syndrome is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. How can gene variants affect health and development? Recommended Surveillance for Individuals with SOX2 Disorder. People with SOX2 anophthalmia syndrome are usually born without eyeballs (anophthalmia), although some individuals have small eyes (microphthalmia). Fielder A, Ainsworth J, Moore A, Read S, Uddin J, Laws D, Pascuel-Salcedo D, Ceroni F, Aguilera-Garcia D, Chassaing N, Bax DA, Blanco-Kelly F, Ramos P, Tarilonte M, Villaverde C, da Silva LRJ, Ballesta-Martnez MJ, Sanchez-Soler MJ, Holt RJ, Cooper-Charles L, Bruty J, Wallis Y, McMullan D, Hoffman J, Bunyan D, Stewart A, Stewart H, Lachlan K, Fryer A, McKay V, Roume J, Dureau P, Saggar A, Griffiths M, Calvas P, Ayuso C, Corton M, Ragge NK, et al. hereby granted to reproduce, distribute, and translate copies of content materials for GeneReviews(R) [Internet]. in the fellow eye. Most cases result from new mutations in the SOX2 gene and occur in people with no history of the disorder in their family. c/o Center for Developmental Medicine and Genetics, A cytogenetically visible deletion of 3q26.33 that either encompasses, Professor Veronica van Heyningen for continued helpful collaboration, MACS family support organization for their interest and support, 30 July 2020 (bp) Comprehensive update posted live, 31 July 2014 (me) Comprehensive update posted live, 25 August 2009 (me) Comprehensive update posted live, 7 March 2008 (cd) Revision: FISH analysis available clinically, 5 December 2007 (cd) Revision: deletion/duplication analysis available clinically. Frequency refers to the number of times the term was used in all included case reports. Glasses or contacts. Br J SOX2 anophthalmia syndrome is a rare disorder characterized by abnormal development of the eyes and other parts of the body. Ages 0-3 years. Community vision services through early intervention or school district, Recurrent variant specifically assoc w/status dystonicus [. This talk should include details on what types of vaccinations you might need to be up-to-date before you get pregnant. The degree of learning disability is not predictable by pathogenic variant type or presence or absence of eye involvement [Dennert et al 2017, Blackburn et al 2018, Errichiello et al 2018]. Bilateral anophthalmia and/or microphthalmia, Unilateral anophthalmia or microphthalmia, Genital abnormalities. SOX2 disorder comprises a phenotypic spectrum that can include anophthalmia and/or microphthalmia, brain malformations, developmental delay / intellectual disability, esophageal atresia, hypogonadotropic hypogonadism (manifest as cryptorchidism and micropenis in males, gonadal dysgenesis infrequently in females, and delayed puberty in both The features of this condition are present from birth. A short animation explaining MAC. Status dystonicus (a movement disorder emergency in which there is prolonged, generalized, intense, and painful muscle contraction) was originally reported in individuals with bilateral anophthalmia and a specific variant (see Genotype-Phenotype Correlations and Table 7) [Gorman et al 2016]; however, other variants, including the most common SOX2 variant, were subsequently associated with this feature in two individuals with bilateral anophthalmia or bilateral optic disc abnormality [Martinez & Madsen 2019, Pilz et al 2019]. Dis. Routine karyotyping with additional FISH analysis if the proband has a deletion of 3q26.33 or other chromosome rearrangement involving 3q26.33, to determine if either parent has a balanced chromosome rearrangement involving the 3q26.33 region. Sequence analysis detects variants that are benign, likely benign, of uncertain significance, likely pathogenic, or pathogenic. Mechanism of disease causation. SOX2 anophthalmia syndrome Also known as: AEG syndrome, Anophthalmia-esophageal-genital syndrome, SOX2-related eye disorders, syndromic microphthalmia 3 About Description and symptoms Communities Support groups for Sox2 Anophthalmia Syndrome Providers Healthcare providers in the area Research Sox2 anophthalmia syndrome is an autosomal dominant inheritance. Microphthalmia - Wikipedia Novel SOX2 mutations and genotype-phenotype correlation in anophthalmia and microphthalmia. IEP services will be reviewed annually to determine whether any changes are needed. SOX2 anophthalmia syndrome - PubMed sox2 anophthalmia syndrome life expectancy In the 174 individuals reported (114 individuals reviewed by Williamson & FitzPatrick [2014] plus 60 individuals reported subsequently), 76 (44%) had bilateral anophthalmia, 23 (13%) had anophthalmia with contralateral microphthalmia, and 20 (12%) had bilateral microphthalmia. GeneReviews [Internet]. Almost all SOX2 pathogenic variants reported to date appear to represent heterozygous loss of function; thus, it is difficult to draw genotype-phenotype correlations. No phenotypes other than those discussed in this GeneReview are known to be associated with heterozygous pathogenic variants in SOX2. Gene-targeted testing requires that the clinician determine which gene(s) are likely involved, whereas comprehensive genomic testing does not. Beyond that, private supportive therapies based on the affected individual's needs may be considered. Status dystonicus, hyperpyrexia, and acute kidney injury in a patient with SOX2-anophthalmia syndrome. The risk to the sibs of the proband depends on the genetic status of the proband's parents: Other family members. Johnston JJ, Williamson KA, Chou CM, Sapp JC, Ansari M, Chapman HM, Cooper DN, Dabir T, Dudley JN, Holt RJ, Ragge NK, Schffer AA, Sen SK, Slavotinek AM, FitzPatrick DR, Glaser TM, Stewart F, Black GC, Biesecker LG. J Clin Posted on June 29, 2022 Kelberman D, de Castro SC, Huang S, Crolla JA, Palmer R, Gregory JW, Taylor D, The following section deals with genetic The information on this site should not be used as a substitute for professional medical care or advice. SOX2 anophthalmia syndrome Luisa Sanctis 2005, American Journal of Medical Genetics Part A Microphthalmia (small eye), anophthalmia (absent eye), and coloboma (failure of optic fissure closure) (MAC) are commonly associated eye malformations with a combined birth incidence of about 2 per 10,000 . Occasionally hypospadias is observed. SOX2 disorder, caused by an intragenic SOX2 pathogenic variant or a deletion of 3q26.33 involving SOX2, is an autosomal dominant disorder. http://www.ncbi.nlm.nih.gov/books/NBK1300/. Biology | Free Full-Text | Genetic Variants in Protein Tyrosine SOX1 (OMIM 602148), SOX2, and SOX3 (OMIM 313430) belong to the B1 subfamily and are expressed in various phases of embryonic development and cell differentiation, in which . See Quick Reference for an explanation of nomenclature. SOX2 anophthalmia syndrome - Ragge - Wiley Online Library SOX2 disorder should be considered in individuals with the following clinical and brain MRI findings and family history. Multiple pages were reviewed for this article. 2008 Nov 1;146A(21):2794-8. doi: More detailed information for clinicians ordering genomic testing can be found here. SOX2 - Oxford Academic Families with limited income and resources may also qualify for supplemental security income (SSI) for their child with a disability. The diagnosis of SOX2 disorder is established in a proband in whom molecular genetic testing identifies either a heterozygous intragenic SOX2 pathogenic (or likely pathogenic) variant or a deletion that is intragenic or a deletion of 3q26.33 involving SOX2 (see Table 1). Edinburgh, United Kingdom, Malformations of the ears, teeth, fingers, skeleton, or genitourinary system, Mild-to-severe ID or DD in ~60% of affected males, Incl best corrected visual acuity, assessment of refractive error, fundus exam. Genital abnormalities. SOX2 anophthalmia syndrome: 12 new cases demonstrating broader Education of parents/caregivers regarding common seizure presentations is appropriate. professional. Hearing device can be helpful but no treatment is available for the eyeball malformations. Congenital anophthalmia is a developmental disorder in which the eye does not develop or is underdeveloped. Introduction. [ Read summary ] Many factors can affect how long a person with Down syndrome lives. In 1960, on average, persons with Down syndrome lived to be about 10 years old. B r J Ophthalmol 2007; 91: 1471 . Guichet A, Triau S, Lepinard C, Esculapavit C, Biquard F, Descamps P, Encha-Razavi F, Bonneau D. Prenatal diagnosis of primary anophthalmia with a 3q27 interstitial deletion involving SOX2. It is so rare it occurs in one in 250,000 people. PDF Two Cases of Anophthalmia and Quality of Life Familial Assess axial & peripheral tone to advise on likely efficacy of antispasmodic medications & procedures. Anophthalmia And Microphthalmia: Symptoms And Treatment - EyeMantra American Academy of Ophthalmology. They may also. Thalidomide treats cancer and some skin conditions. information on the nature, mode(s) of inheritance, and implications of genetic disorders to help them Special education law requires that children participating in an IEP be in the least restrictive environment feasible at school and included in general education as much as possible, when and where appropriate. Before placement, an evaluation is made to determine needed services and therapies and an individualized education plan (IEP) is developed for those who qualify based on established motor, language, social, or cognitive delay. Martinez E, Madsen EC. Expansion of the Human Phenotype Ontology (HPO) knowledge base and resources. Consultation with a developmental pediatrician may be helpful in guiding parents through appropriate behavior management strategies or providing prescription medications, such as medication used to treat attention-deficit/hyperactivity disorder, when necessary. Infancy, mid-childhood, then every 3-6 mos from age 8 yrs, Every 3-6 mos during childhood or w/any progression of symptoms or signs, or deteriorating function, Most common pathogenic variant; accounts for ~20% of all pathogenic variants [, Recurrent familial variant assoc w/broad range of ocular phenotypes [. The evaluation will consider cognitive abilities and sensory impairments to determine the most appropriate form of communication. Williamson KA, Hever AM, Rainger J, Rogers RC, Magee A, Fiedler Z, Keng WT, Less frequent variants, esp those that alter residues adjacent to Tyr160, are also assoc w/severe phenotype. It encompasses all individuals with a SOX2 pathogenic variant who should be evaluated for medically actionable manifestations across the entire phenotypic spectrum (regardless of clinical findings that prompted molecular genetic testing). The SOX2 phenotypes include a patient with anophthalmia, oesophageal abnormalities and horseshoe kidney, and a patient with a retinal dystrophy implicating SOX2 in retinal development. This phenomenon is called germline mosaicism. Variable expressivity is observed with some recurrent pathogenic variants (Table 7). Congenital anophthalmia and microphthalmia are rare developmental defects of the globe. CMA designs in current clinical use target the 3q26.33 region. SOX2 is a single exon transcription factor previously associated with anophthalmia [ 18, 19 ], microphthalmia [ 20 ], and coloboma [ 21 ]. Schneider A, Bardakjian TM, Zhou J, Hughes N, Keep R, Dorsainville D, Kherani F, Katowitz J, Schimmenti LA, Hummel M, Fitzpatrick DR, Young TL. Anophthalmia (Concept Id: C0003119) - National Center for Biotechnology Sisodiya SM, Ragge NK, Cavalleri GL, Hever A, Lorenz B, Schneider A, Williamson KA, Stevens JM, Free SL, Thompson PJ, van Heyningen V, Fitzpatrick DR. Role of SOX2 mutations in human hippocampal malformations and epilepsy. 2007 Nov;91(11):1471-6. doi: 10.1136/bjo.2007.117929. Washington) are included with each copy; (ii) a link to the original material is provided sox2 anophthalmia syndrome life expectancy make informed medical and personal decisions. Q11.1 - Other anophthalmos - ICD List 2023 In addition to a pediatrician or internist, someone with either of these conditions will probably need an ophthalmologist, an ocularist and an oculoplastic surgeon. SOX2 anophthalmia syndrome is a rare disorder characterized by abnormal development of the eyes and other parts of the body. GeneReviews follows the standard naming conventions of the Human Genome Variation Society (varnomen.hgvs.org). Shah SP, Taylor AE, Sowden JC, Ragge NK, Russell-Eggitt I, Rahi JS, Gilbert CE, et al. The SOX2 protein regulates the activity of other genes, especially those that are important for normal development of the eyes. To establish the extent of disease and needs in an individual diagnosed with SOX2 disorder, the evaluations summarized in Table 4 (if not performed as part of the evaluation that led to diagnosis) are recommended. Severe genital but no major ocular anomalies in a female patient with the recurrent c.70del20 variant. However, there are treatments that include: Theres no way to completely eliminate your risk of microphthalmia and anophthalmia, but there are ways to make pregnancy safer: Theres no cure for microphthalmia or anophthalmia. If a parent has a balanced structural chromosome rearrangement involving the 3q26.33 region, the risk to sibs is increased. Bakrania P, Robinson DO, Bunyan DJ, et al. Anophthalmos, microphthalmos, and typical coloboma in the United Kingdom: a prospective study of incidence and risk. This is an autosomal dominant disorder secondary to heterozygous mutations in the SOX2 gene (3q26.33). There are other things that may be factors in these eye conditions, including: In a newborn child, your provider can diagnose anophthalmia and microphthalmia through an examination. Make sure you get prenatal care (care before birth) early and consistently. The mutation of the sox2 gene causes sox2 Anophthalmia syndrome. This gene provides instructions for making a protein that plays a critical role in the formation of many different tissues and organs during embryonic development. Syndromic microphthalmia, type 3 - Living with the Disease - Genetic Novel SOX2 partner-factor domain mutation in a four-generation family. The phenotypic spectrum of SOX2 disorder includes anophthalmia and/or microphthalmia, brain malformations, developmental delay/ intellectual disability, esophageal atresia, hypogonadotropic hypogonadism (manifest as cryptorchidism and micropenis in males, gonadal dysgenesis infrequently in females, and delayed puberty in both sexes), pituitary hypoplasia, postnatal growth delay, hypotonia, seizures, and spastic or dystonic movements. 2007 Nov 26;2:47. doi: 10.1186/1750-1172-2-47. Prostheses: Consider optically clear expanders to stimulate growth of the orbit & periorbital tissues. Brain MRI. Fantes J, Ragge NK, Lynch SA, McGill NI, Collin JR, Howard-Peebles PN, Hayward C, Vivian AJ, Williamson K, van Heyningen V, FitzPatrick DR. Mutations in SOX2 cause anophthalmia. The N-terminal region is of unknown function and contains short polyglycine and polyalanine repeats. SOX2 Anophthalmia Syndrome | Encyclopedia MDPI Bilateral anophthalmia and/or microphthalmia. Spasticity, including diplegia, paraparesis, or quadriparesis was reported in 13 individuals. The optimal time for determination of genetic risk and discussion of the availability of prenatal/preimplantation genetic testing is before pregnancy. One of these individuals, who also had a dystonic movement disorder and unilateral strabismus as the only eye defect, had a 1.6- to 2-megabase (Mb) deletion encompassing SOX2 [Dennert et al 2017]. Zhou J, Kherani F, Bardakjian TM, Katowitz J, Hughes N, Schimmenti LA, Schneider A, Young TL. A practical guide to the management of anophthalmia and - Nature This is a rare disorder that can cause a child to be born without eyeballs. When anophthalmia or microphthalmia is the only condition a baby has, it's called nonsyndromic or isolated. The eyes are often absent or severely underdeveloped (anophthalmia), or they may be abnormally small (microphthalmia). HGNC; Cleveland Clinic is a non-profit academic medical center. Multiple pages were reviewed for this article. Mauri L, Franzoni A, Scarcello M, Sala S, Garavelli L, Modugno A, Grammatico P, Patrosso MC, Piozzi E, Del Longo A, Gesu GP, Manfredini E, Primignani P, Damante G, Penco S. SOX2, OTX2 and PAX6 analysis in subjects with anophthalmia and microphthalmia. Suzuki J, Azuma N, Dateki S, Soneda S, Muroya K, Yamamoto Y, Saito R, Sano S, Nagai T, Wada H, Endo A, Urakami T, Ogata T, Fukami M. Mutation spectrum and phenotypic variation in nine patients with SOX2 abnormalities. Treatment of manifestations: Treatment usually involves a multidisciplinary team including as needed an experienced pediatric ophthalmologist, ophthalmo-plastic surgeon (for children with anophthalmia and/or extreme microphthalmia), and early educational intervention through community vision services and/or school district; educational support for school-age children; pediatric endocrinologist; pediatric neurologist; and physical therapist and occupational therapist. Together they are the most common cause of childhood sight impairment registration in England and Wales (18.4% of children). Optic fissure closure defects have been reported but are not a common feature. [Google Scholar] 10. All ages. Policy. Both the globe (human eye) and the ocular tissue are missing from the orbit. Hagstrom SA et al: 20126410: 2010: SOX2 is an oncogene activated by recurrent 3q26.3 amplifications in human lung squamous cell carcinomas. The genetic architecture of microphthalmia, anophthalmia and coloboma. Familial recurrence of SOX2 anophthalmia syndrome: Phenotypically Williamson KA, Yates TM, FitzPatrick DR. SOX2 Disorder. distributors, and/or translators comply with the GeneReviews Copyright Notice and Usage support organizations and/or registries for the benefit of individuals with this disorder These early intervention services will help babies learn to walk, talk and interact with others. Ted's story - MACS - Microphthalmia, Anophthalmia and Coloboma Support Reference to "pathogenic variants" in this section is understood to include any likely pathogenic variants. 15 A family history of anophthalmia was present in . Epub 2008 BMP4 loss-of-function mutations in developmental eye disorders including SHORT syndrome. Sensorineural hearing loss. sox2 anophthalmia syndrome life expectancy. Ages 3-5 years. Note on Table A, Locus-Specific Databases: See also the DECIPHER database. Some issues to consider: Consider evaluation for alternative means of communication (e.g., augmentative and alternative communication [AAC]) for individuals who have expressive language difficulties. Gerth-Kahlert C, Williamson K, Ansari M, Rainger JK, Hingst V, Zimmermann T, Tech S, Guthoff RF, van Heyningen V, Fitzpatrick DR. Clinical and mutation analysis of 51 probands with anophthalmia and/or severe microphthalmia from a single center. Microphthalmia & Anophthalmia: Types, Symptoms & Treatment as in some patients with SOX2 . The risk to other family members depends on the genetic status of the proband's parents: if a parent has the causative genetic alteration or a balanced structural chromosome rearrangement, the parent's family members may be at risk. demonstrating broader phenotype and high frequency of large gene deletions. Genes of Interest in the Differential Diagnosis of SOX2 Disorder. The ' SOX2 anophthalmia syndrome' encompasses sclerocornea, cataracts, persistent hyperplastic primary vitreous and optic disc dysplasia as well as non-ocular features like mental retardation, neurological abnormalities, facial dysmorphisms, post-natal growth failure, oesophageal pathology and anomalies of male genitalia [ 14, 15 ]. In females, malformations are less frequent and can include hypoplastic or hemi-uterus, ovary or vaginal agenesis, and vaginal adhesions [Errichiello et al 2018]. 5. It has been called also the SOX 2 anophthalmia syndrome 3 due to the frequent mutations and/or deletions found in the SOX2 gene. Zhou J, Kherani F, Bardakjian TM, Katowitz J, Hughes N, Schimmenti LA, These major malformations constitute a surgical emergency. sox2 anophthalmia syndrome life expectancy Triple X syndrome. When the phenotypic findings suggest the diagnosis of SOX2 disorder, molecular genetic testing approaches can include single-gene testing or use of a multigene panel: Comprehensive Facts about Anophthalmia / Microphthalmia. how did edd gould get cancer. We suggest that such deletions could be a relatively common cause of SOX2 anophthalmia syndrome and both tests should be included in the initial diagnostic . Affected families are of Middle Eastern ethnicity. ), (https://www.marchofdimes.org/complications/anophthalmia-and-microphthalmia.aspx), (https://medlineplus.gov/genetics/condition/sox2-anophthalmia-syndrome/#references). MRC Institute of Genetics and Molecular Medicine SOX2 anophthalmia syndrome. - Abstract - Europe PMC (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6133583/), Visitation, mask requirements and COVID-19 information, Coloboma: A coloboma means that tissue is missing in the eye. SOX2 anophthalmia syndrome: 12 new cases demonstrating broader Khler S, Carmody L, Vasilevsky N, Jacobsen JOB, Danis D, Gourdine JP, Gargano M, Harris NL, Matentzoglu N, McMurry JA, Osumi-Sutherland D, Cipriani V, Balhoff JP, Conlin T, Blau H, Baynam G, Palmer R, Gratian D, Dawkins H, Segal M, Jansen AC, Muaz A, Chang WH, Bergerson J, Laulederkind SJF, Yksel Z, Beltran S, Freeman AF, Sergouniotis PI, Durkin D, Storm AL, Hanauer M, Brudno M, Bello SM, Sincan M, Rageth K, Wheeler MT, Oegema R, Lourghi H, Della Rocca MG, Thompson R, Castellanos F, Priest J, Cunningham-Rundles C, Hegde A, Lovering RC, Hajek C, Olry A, Notarangelo L, Similuk M, Zhang XA, Gmez-Andrs D, Lochmller H, Dollfus H, Rosenzweig S, Marwaha S, Rath A, Sullivan K, Smith C, Milner JD, Leroux D, Boerkoel CF, Klion A, Carter MC, Groza T, Smedley D, Haendel MA, Mungall C, Robinson PN.
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