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Cranioectodermal dysplasia 1(CED1)

MedGen UID:
96586
Concept ID:
C0432235
Disease or Syndrome
Synonyms: CED1; Levin syndrome 1; LEVIN SYNDROME I
 
Gene (location): IFT122 (3q21.3-22.1)
 
Monarch Initiative: MONDO:0021093
OMIM®: 218330

Disease characteristics

Excerpted from the GeneReview: Cranioectodermal Dysplasia
Cranioectodermal dysplasia (CED) is a ciliopathy with skeletal involvement (narrow thorax, shortened proximal limbs, syndactyly, polydactyly, brachydactyly), ectodermal features (widely spaced hypoplastic teeth, hypodontia, sparse hair, skin laxity, abnormal nails), joint laxity, growth deficiency, and characteristic facial features (frontal bossing, low-set simple ears, high forehead, telecanthus, epicanthal folds, full cheeks, everted lower lip). Most affected children develop nephronophthisis that often leads to end-stage kidney disease in infancy or childhood, a major cause of morbidity and mortality. Hepatic fibrosis and retinal dystrophy are also observed. Dolichocephaly, often secondary to sagittal craniosynostosis, is a primary manifestation that distinguishes CED from most other ciliopathies. Brain malformations and developmental delay may also occur. [from GeneReviews]
Authors:
Weizhen Tan  |  Angela Lin  |  Kim Keppler-Noreuil   view full author information

Additional description

From MedlinePlus Genetics
Cranioectodermal dysplasia is a disorder that affects many parts of the body. The most common features involve bone abnormalities and abnormal development of certain tissues known as ectodermal tissues, which include the skin, hair, nails, and teeth. The signs and symptoms of this condition vary among affected individuals, even among members of the same family.

Distinctive abnormalities of the skull and face are common in people with cranioectodermal dysplasia. Most affected individuals have a prominent forehead (frontal bossing) and an elongated head (dolichocephaly) due to abnormal fusion of certain skull bones (sagittal craniosynostosis). A variety of facial abnormalities can occur in people with this condition; these include low-set ears that may also be rotated backward, an increased distance between the inner corners of the eyes (telecanthus), and outside corners of the eyes that point upward or downward (upslanting or downslanting palpebral fissures) among others.

Development of bones in the rest of the skeleton is also affected in this condition. Abnormalities in the long bones of the arms and legs (metaphyseal dysplasia) lead to short limbs and short stature. In addition, affected individuals often have short fingers (brachydactyly). Some people with this condition have short rib bones and a narrow rib cage, which can cause breathing problems, especially in affected newborns.

Cranioectodermal dysplasia can affect additional organs and tissues in the body. A kidney disorder known as nephronophthisis occurs in many people with this condition, and it can lead to a life-threatening failure of kidney function known as end-stage renal disease. Abnormalities of the liver, heart, or eyes also occur in people with cranioectodermal dysplasia.

Abnormal development of ectodermal tissues in people with cranioectodermal dysplasia can lead to sparse hair, small or missing teeth, short fingernails and toenails, and loose skin.  https://medlineplus.gov/genetics/condition/cranioectodermal-dysplasia

Clinical features

From HPO
Interstitial nephritis
MedGen UID:
11952
Concept ID:
C0041349
Disease or Syndrome
A form of inflammation of the kidney affecting the interstitium of the kidneys surrounding the tubules.
Chronic kidney disease
MedGen UID:
473458
Concept ID:
C1561643
Disease or Syndrome
Functional anomaly of the kidney persisting for at least three months.
Stage 1 chronic kidney disease
MedGen UID:
378390
Concept ID:
C2316401
Disease or Syndrome
A type of chronic kidney disease with normal or increased glomerular filtration rate (GFR at least 90 mL/min/1.73 m2).
Stage 5 chronic kidney disease
MedGen UID:
384526
Concept ID:
C2316810
Disease or Syndrome
A degree of kidney failure severe enough to require dialysis or kidney transplantation for survival characterized by a severe reduction in glomerular filtration rate (less than 15 ml/min/1.73 m2) and other manifestations including increased serum creatinine.
Renal magnesium wasting
MedGen UID:
1811452
Concept ID:
C5574944
Finding
High urine magnesium in the presence of hypomagnesemia.
Brachydactyly
MedGen UID:
67454
Concept ID:
C0221357
Congenital Abnormality
Digits that appear disproportionately short compared to the hand/foot. The word brachydactyly is used here to describe a series distinct patterns of shortened digits (brachydactyly types A-E). This is the sense used here.
Single transverse palmar crease
MedGen UID:
96108
Concept ID:
C0424731
Finding
The distal and proximal transverse palmar creases are merged into a single transverse palmar crease.
Triphalangeal hallux
MedGen UID:
609308
Concept ID:
C0432034
Congenital Abnormality
A hallux (big toe) with three phalanges in a single, proximo-distal axis.
Short humerus
MedGen UID:
316907
Concept ID:
C1832117
Congenital Abnormality
Underdevelopment of the humerus.
Fibular hypoplasia
MedGen UID:
316909
Concept ID:
C1832119
Finding
Underdevelopment of the fibula.
Radial deviation of finger
MedGen UID:
322852
Concept ID:
C1836189
Finding
Bending or curvature of a finger toward the radial side (i.e., towards the thumb). The deviation is at the metacarpal-phalangeal joint, and this finding is distinct from clinodactyly.
Short toe
MedGen UID:
322858
Concept ID:
C1836195
Finding
A toe that appears disproportionately short compared to the foot.
Short distal phalanx of finger
MedGen UID:
326590
Concept ID:
C1839829
Finding
Short distance from the end of the finger to the most distal interphalangeal crease or the distal interphalangeal joint flexion point. That is, hypoplasia of one or more of the distal phalanx of finger.
Broad toe
MedGen UID:
351283
Concept ID:
C1865038
Finding
Visible increase in width of the non-hallux digit without an increase in the dorso-ventral dimension.
Rhizomelia
MedGen UID:
357122
Concept ID:
C1866730
Congenital Abnormality
Disproportionate shortening of the proximal segment of limbs (i.e. the femur and humerus).
Broad distal phalanges of all fingers
MedGen UID:
869745
Concept ID:
C4024174
Anatomical Abnormality
Abnormally wide (broad) distal phalanx of finger of all fingers.
Clinodactyly
MedGen UID:
1644094
Concept ID:
C4551485
Congenital Abnormality
An angulation of a digit at an interphalangeal joint in the plane of the palm (finger) or sole (toe).
Bicuspid aortic valve
MedGen UID:
57436
Concept ID:
C0149630
Congenital Abnormality
Aortic valve disease-2 (AOVD2) is characterized by bicuspid aortic valve (BAV) and dilation of the ascending aorta. Calcification of the valve and the aorta has been observed, and some patients exhibit coarctation of the aorta (Tan et al., 2012; Luyckx et al., 2019; Park et al., 2019). For a general phenotypic description and a discussion of genetic heterogeneity of aortic valve disease, see AOVD1 (109730).
Hepatomegaly
MedGen UID:
42428
Concept ID:
C0019209
Finding
Abnormally increased size of the liver.
Liver failure
MedGen UID:
88444
Concept ID:
C0085605
Disease or Syndrome
A disorder characterized by the inability of the liver to metabolize chemicals in the body. Causes include cirrhosis and drug-induced hepatotoxicity. Signs and symptoms include jaundice and encephalopathy. Laboratory test results reveal abnormal plasma levels of ammonia, bilirubin, lactic dehydrogenase, and alkaline phosphatase.
Hepatic fibrosis
MedGen UID:
116093
Concept ID:
C0239946
Disease or Syndrome
The presence of excessive fibrous connective tissue in the liver. Fibrosis is a reparative or reactive process.
Hepatic cysts
MedGen UID:
82761
Concept ID:
C0267834
Disease or Syndrome
A cystic lesion located in the liver.
Protuberant abdomen
MedGen UID:
340750
Concept ID:
C1854928
Finding
A thrusting or bulging out of the abdomen.
Malformation of the hepatic ductal plate
MedGen UID:
346605
Concept ID:
C1857519
Finding
Low-set ears
MedGen UID:
65980
Concept ID:
C0239234
Congenital Abnormality
Upper insertion of the ear to the scalp below an imaginary horizontal line drawn between the inner canthi of the eye and extending posteriorly to the ear.
Protruding ear
MedGen UID:
343309
Concept ID:
C1855285
Finding
Angle formed by the plane of the ear and the mastoid bone greater than the 97th centile for age (objective); or, outer edge of the helix more than 2 cm from the mastoid at the point of maximum distance (objective).
Intellectual disability
MedGen UID:
811461
Concept ID:
C3714756
Mental or Behavioral Dysfunction
Intellectual disability, previously referred to as mental retardation, is characterized by subnormal intellectual functioning that occurs during the developmental period. It is defined by an IQ score below 70.
Inguinal hernia
MedGen UID:
6817
Concept ID:
C0019294
Finding
Protrusion of the contents of the abdominal cavity through the inguinal canal.
Osteoporosis
MedGen UID:
14535
Concept ID:
C0029456
Disease or Syndrome
Osteoporosis is a systemic skeletal disease characterized by low bone density and microarchitectural deterioration of bone tissue with a consequent increase in bone fragility. According to the WHO criteria, osteoporosis is defined as a BMD that lies 2.5 standard deviations or more below the average value for young healthy adults (a T-score below -2.5 SD).
Frontal bossing
MedGen UID:
67453
Concept ID:
C0221354
Congenital Abnormality
Bilateral bulging of the lateral frontal bone prominences with relative sparing of the midline.
Dolichocephaly
MedGen UID:
65142
Concept ID:
C0221358
Congenital Abnormality
An abnormality of skull shape characterized by a increased anterior-posterior diameter, i.e., an increased antero-posterior dimension of the skull. Cephalic index less than 76%. Alternatively, an apparently increased antero-posterior length of the head compared to width. Often due to premature closure of the sagittal suture.
Isolated scaphocephaly
MedGen UID:
82712
Concept ID:
C0265534
Congenital Abnormality
Scaphocephaly is a subtype of dolichocephaly where the anterior and posterior aspects of the cranial vault are pointed (boat-shaped). Scaphocephaly is caused by a precocious fusion of sagittal suture without other associated synostosis.
Short thorax
MedGen UID:
140876
Concept ID:
C0426789
Finding
Reduced inferior to superior extent of the thorax.
Narrow chest
MedGen UID:
96528
Concept ID:
C0426790
Finding
Reduced width of the chest from side to side, associated with a reduced distance from the sternal notch to the tip of the shoulder.
Short ribs
MedGen UID:
98094
Concept ID:
C0426817
Finding
Reduced rib length.
Sagittal craniosynostosis
MedGen UID:
140921
Concept ID:
C0432123
Congenital Abnormality
A kind of craniosynostosis affecting the sagittal suture.
Joint hypermobility
MedGen UID:
336793
Concept ID:
C1844820
Finding
The capability that a joint (or a group of joints) has to move, passively and/or actively, beyond normal limits along physiological axes.
Flattened epiphysis
MedGen UID:
387844
Concept ID:
C1857527
Finding
Abnormal flatness (decreased height) of epiphyses.
Pectus excavatum
MedGen UID:
781174
Concept ID:
C2051831
Finding
A defect of the chest wall characterized by a depression of the sternum, giving the chest ("pectus") a caved-in ("excavatum") appearance.
Recurrent respiratory infections
MedGen UID:
812812
Concept ID:
C3806482
Finding
An increased susceptibility to respiratory infections as manifested by a history of recurrent respiratory infections.
Hypocalcemia
MedGen UID:
5705
Concept ID:
C0020598
Disease or Syndrome
An abnormally decreased calcium concentration in the blood.
Enamel hypoplasia
MedGen UID:
3730
Concept ID:
C0011351
Disease or Syndrome
Developmental hypoplasia of the dental enamel.
Partial congenital absence of teeth
MedGen UID:
43794
Concept ID:
C0020608
Congenital Abnormality
Tooth agenesis in some form is a common human anomaly that affects approximately 20% of the population. Although tooth agenesis is associated with numerous syndromes, several case reports describe nonsyndromic forms that are either sporadic or familial in nature, as reviewed by Gorlin et al. (1990). The incidence of familial tooth agenesis varies with each class of teeth. Most commonly affected are third molars (wisdom teeth), followed by either upper lateral incisors or lower second premolars; agenesis involving first and second molars is very rare. Also see 114600 and 302400. Selective tooth agenesis without associated systemic disorders has sometimes been divided into 2 types: oligodontia, defined as agenesis of 6 or more permanent teeth, and hypodontia, defined as agenesis of less than 6 teeth. The number in both cases does not include absence of third molars (wisdom teeth). Faulty use of the terms, however, have confounded their use. The term 'partial anodontia' is obsolete (Salinas, 1978). Genetic Heterogeneity of Selective Tooth Agenesis Other forms of selective tooth agenesis include STHAG2 (602639), mapped to chromosome 16q12; STHAG3 (604625), caused by mutation in the PAX9 gene (167416) on chromosome 14q12; STHAG4 (150400), caused by mutation in the WNT10A gene (606268) on chromosome 2q35; STHAG5 (610926), mapped to chromosome 10q11; STHAG7 (616724), caused by mutation in the LRP6 gene (603507) on chromosome 12p13; STHAG8 (617073), caused by mutation in the WNT10B gene (601906) on chromosome 12q13; STHAG9 (617275), caused by mutation in the GREM2 gene (608832) on chromosome 1q43; STHAG10 (620173), caused by mutation in the TSPEAR gene (612920) on chromosome 21q22; and STHAGX1 (313500), caused by mutation in the EDA gene (300451) on chromosome Xq13. A type of selective tooth agenesis that was formerly designated STHAG6 has been incorporated into the dental anomalies and short stature syndrome (DASS; 601216). Of 34 unrelated patients with nonsyndromic tooth agenesis, van den Boogaard et al. (2012) found that 56% (19 patients) had mutations in the WNT10A gene (STHAG4), whereas only 3% and 9% had mutations in the MSX1 (STHAG1) and PAX9 (STHAG3) genes, respectively. The authors concluded that WNT10A is a major gene in the etiology of isolated hypodontia. Genotype-Phenotype Correlations Yu et al. (2016) observed that the most frequently missing permanent teeth in WNT10B-associated oligodontia were the lateral incisors (83.3%), whereas premolars were missing only 51.4% of the time, which they noted was a pattern 'clearly different' from the oligodontia patterns resulting from WNT10A mutations. They also stated that the selective pattern in WNT10B mutants was different from that associated with mutations in other genes, such as MSX1, in which second premolars are missing, and PAX9, in which there is agenesis of molars.
High forehead
MedGen UID:
65991
Concept ID:
C0239676
Finding
An abnormally increased height of the forehead.
Microdontia
MedGen UID:
66008
Concept ID:
C0240340
Congenital Abnormality
Decreased size of the teeth, which can be defined as a mesiodistal tooth diameter (width) more than 2 SD below mean. Alternatively, an apparently decreased maximum width of tooth.
High palate
MedGen UID:
66814
Concept ID:
C0240635
Congenital Abnormality
Height of the palate more than 2 SD above the mean (objective) or palatal height at the level of the first permanent molar more than twice the height of the teeth (subjective).
Anodontia
MedGen UID:
98313
Concept ID:
C0399352
Congenital Abnormality
The absence of all teeth from the normal series by a failure to develop.
Telecanthus
MedGen UID:
140836
Concept ID:
C0423113
Finding
Distance between the inner canthi more than two standard deviations above the mean (objective); or, apparently increased distance between the inner canthi.
Epicanthus
MedGen UID:
151862
Concept ID:
C0678230
Congenital Abnormality
Epicanthus is a condition in which a fold of skin stretches from the upper to the lower eyelid, partially covering the inner canthus. Usher (1935) noted that epicanthus is a normal finding in the fetus of all races. Epicanthus also occurs in association with hereditary ptosis (110100).
High, narrow palate
MedGen UID:
324787
Concept ID:
C1837404
Finding
The presence of a high and narrow palate.
Anteverted nares
MedGen UID:
326648
Concept ID:
C1840077
Finding
Anteriorly-facing nostrils viewed with the head in the Frankfurt horizontal and the eyes of the observer level with the eyes of the subject. This gives the appearance of an upturned nose (upturned nasal tip).
Widely spaced teeth
MedGen UID:
337093
Concept ID:
C1844813
Finding
Increased spaces (diastemata) between most of the teeth in the same dental arch.
Wide nasal bridge
MedGen UID:
341441
Concept ID:
C1849367
Finding
Increased breadth of the nasal bridge (and with it, the nasal root).
Everted lower lip vermilion
MedGen UID:
344003
Concept ID:
C1853246
Finding
An abnormal configuration of the lower lip such that it is turned outward i.e., everted, with the Inner aspect of the lower lip vermilion (normally opposing the teeth) being visible in a frontal view.
Full cheeks
MedGen UID:
355661
Concept ID:
C1866231
Finding
Increased prominence or roundness of soft tissues between zygomata and mandible.
Ectodermal dysplasia
MedGen UID:
8544
Concept ID:
C0013575
Disease or Syndrome
Ectodermal dysplasia is a group of conditions in which there is abnormal development of the skin, hair, nails, teeth, or sweat glands.
Short nail
MedGen UID:
140850
Concept ID:
C0423808
Finding
Decreased length of nail.
Thin nail
MedGen UID:
98073
Concept ID:
C0423823
Finding
Nail that appears thin when viewed on end.
Fine hair
MedGen UID:
98401
Concept ID:
C0423867
Finding
Hair that is fine or thin to the touch.
Slow-growing hair
MedGen UID:
371309
Concept ID:
C1832348
Finding
Hair whose growth is slower than normal.
Sparse hair
MedGen UID:
1790211
Concept ID:
C5551005
Finding
Reduced density of hairs.
Myopia
MedGen UID:
44558
Concept ID:
C0027092
Disease or Syndrome
Nearsightedness, also known as myopia, is an eye condition that causes blurry distance vision. People who are nearsighted have more trouble seeing things that are far away (such as when driving) than things that are close up (such as when reading or using a computer). If it is not treated with corrective lenses or surgery, nearsightedness can lead to squinting, eyestrain, headaches, and significant visual impairment.\n\nNearsightedness usually begins in childhood or adolescence. It tends to worsen with age until adulthood, when it may stop getting worse (stabilize). In some people, nearsightedness improves in later adulthood.\n\nFor normal vision, light passes through the clear cornea at the front of the eye and is focused by the lens onto the surface of the retina, which is the lining of the back of the eye that contains light-sensing cells. People who are nearsighted typically have eyeballs that are too long from front to back. As a result, light entering the eye is focused too far forward, in front of the retina instead of on its surface. It is this change that causes distant objects to appear blurry. The longer the eyeball is, the farther forward light rays will be focused and the more severely nearsighted a person will be.\n\nNearsightedness is measured by how powerful a lens must be to correct it. The standard unit of lens power is called a diopter. Negative (minus) powered lenses are used to correct nearsightedness. The more severe a person's nearsightedness, the larger the number of diopters required for correction. In an individual with nearsightedness, one eye may be more nearsighted than the other.\n\nEye doctors often refer to nearsightedness less than -5 or -6 diopters as "common myopia." Nearsightedness of -6 diopters or more is commonly called "high myopia." This distinction is important because high myopia increases a person's risk of developing other eye problems that can lead to permanent vision loss or blindness. These problems include tearing and detachment of the retina, clouding of the lens (cataract), and an eye disease called glaucoma that is usually related to increased pressure within the eye. The risk of these other eye problems increases with the severity of the nearsightedness. The term "pathological myopia" is used to describe cases in which high myopia leads to tissue damage within the eye.
Nystagmus
MedGen UID:
45166
Concept ID:
C0028738
Disease or Syndrome
Rhythmic, involuntary oscillations of one or both eyes related to abnormality in fixation, conjugate gaze, or vestibular mechanisms.
Hypotelorism
MedGen UID:
96107
Concept ID:
C0424711
Finding
Interpupillary distance less than 2 SD below the mean (alternatively, the appearance of an decreased interpupillary distance or closely spaced eyes).
Retinal dystrophy
MedGen UID:
208903
Concept ID:
C0854723
Finding
Retinal dystrophy is an abnormality of the retina associated with a hereditary process. Retinal dystrophies are defined by their predominantly monogenic inheritance and they are frequently associated with loss or dysfunction of photoreceptor cells as a primary or secondary event.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
Follow this link to review classifications for Cranioectodermal dysplasia 1 in Orphanet.

Recent clinical studies

Etiology

Walczak-Sztulpa J, Wawrocka A, Leszczynska B, Mikulska B, Arts HH, Bukowska-Olech E, Daniel M, Krawczynski MR, Latos-Bielenska A, Obersztyn E
Am J Med Genet A 2020 Oct;182(10):2417-2425. Epub 2020 Aug 17 doi: 10.1002/ajmg.a.61785. PMID: 32804427
Cha S, Lim JE, Park AY, Do JH, Lee SW, Shin C, Cho NH, Kang JO, Nam JM, Kim JS, Woo KM, Lee SH, Kim JY, Oh B
BMC Genomics 2018 Jun 19;19(1):481. doi: 10.1186/s12864-018-4865-9. PMID: 29921221Free PMC Article
Halbritter J, Bizet AA, Schmidts M, Porath JD, Braun DA, Gee HY, McInerney-Leo AM, Krug P, Filhol E, Davis EE, Airik R, Czarnecki PG, Lehman AM, Trnka P, Nitschké P, Bole-Feysot C, Schueler M, Knebelmann B, Burtey S, Szabó AJ, Tory K, Leo PJ, Gardiner B, McKenzie FA, Zankl A, Brown MA, Hartley JL, Maher ER, Li C, Leroux MR, Scambler PJ, Zhan SH, Jones SJ, Kayserili H, Tuysuz B, Moorani KN, Constantinescu A, Krantz ID, Kaplan BS, Shah JV; UK10K Consortium, Hurd TW, Doherty D, Katsanis N, Duncan EL, Otto EA, Beales PL, Mitchison HM, Saunier S, Hildebrandt F
Am J Hum Genet 2013 Nov 7;93(5):915-25. Epub 2013 Oct 17 doi: 10.1016/j.ajhg.2013.09.012. PMID: 24140113Free PMC Article

Diagnosis

Li L, Liu C, Tian M, Li G, Li J
BMC Pediatr 2023 Aug 18;23(1):407. doi: 10.1186/s12887-023-04110-1. PMID: 37596520Free PMC Article
Walczak-Sztulpa J, Wawrocka A, Leszczynska B, Mikulska B, Arts HH, Bukowska-Olech E, Daniel M, Krawczynski MR, Latos-Bielenska A, Obersztyn E
Am J Med Genet A 2020 Oct;182(10):2417-2425. Epub 2020 Aug 17 doi: 10.1002/ajmg.a.61785. PMID: 32804427
Adamiok-Ostrowska A, Piekiełko-Witkowska A
Cells 2020 Apr 8;9(4) doi: 10.3390/cells9040907. PMID: 32276433Free PMC Article
Zhang W, Taylor SP, Ennis HA, Forlenza KN, Duran I, Li B, Sanchez JAO, Nevarez L, Nickerson DA, Bamshad M; University of Washington Center for Mendelian Genomics, Lachman RS, Krakow D, Cohn DH
Hum Mutat 2018 Jan;39(1):152-166. Epub 2017 Nov 6 doi: 10.1002/humu.23362. PMID: 29068549Free PMC Article
Antony D, Nampoory N, Bacchelli C, Melhem M, Wu K, James CT, Beales PL, Hubank M, Thomas D, Mashankar A, Behbehani K, Schmidts M, Alsmadi O
Eur J Med Genet 2017 Dec;60(12):658-666. Epub 2017 Sep 12 doi: 10.1016/j.ejmg.2017.08.019. PMID: 28870638

Prognosis

Adamiok-Ostrowska A, Piekiełko-Witkowska A
Cells 2020 Apr 8;9(4) doi: 10.3390/cells9040907. PMID: 32276433Free PMC Article

Clinical prediction guides

Ryan R, Failler M, Reilly ML, Garfa-Traore M, Delous M, Filhol E, Reboul T, Bole-Feysot C, Nitschké P, Baudouin V, Amselem S, Escudier E, Legendre M, Benmerah A, Saunier S
Hum Mol Genet 2018 Jan 15;27(2):266-282. doi: 10.1093/hmg/ddx396. PMID: 29121203
Hampl M, Cela P, Szabo-Rogers HL, Kunova Bosakova M, Dosedelova H, Krejci P, Buchtova M
J Dent Res 2017 Aug;96(9):965-974. Epub 2017 Jun 12 doi: 10.1177/0022034517713688. PMID: 28605602Free PMC Article

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