scholarly journals Short Stature Homeobox-Containing Haploinsufficiency in Seven Siblings with Short Stature

2017 ◽  
Vol 2017 ◽  
pp. 1-5
Author(s):  
Elizabeth S. Sandberg ◽  
Ali S. Calikoglu ◽  
Karen J. Loechner ◽  
Lydia L. Snyder
Keyword(s):  
Growth Hormone ◽  
Short Stature ◽  
Index Case ◽  
Standard Deviation Score ◽  
Nucleotide Position ◽  
Height Standard Deviation Score ◽  
Past Medical History ◽  
Shox Gene ◽  
Arm Span ◽  
Gene Index

Deficiency of the short stature homeobox-containing (SHOX) gene is a frequent cause of short stature in children (2–15%). Here, we report 7 siblings with SHOX deficiency due to a point mutation in the SHOX gene. Index case was a 3-year-old male who presented for evaluation of short stature. His past medical history and birth history were unremarkable. Family history was notable for multiple individuals with short stature. Physical exam revealed short stature, with height standard deviation score (SDS) of −2.98, as well as arm span 3 cm less than his height. His laboratory workup was noncontributory for common etiologies of short stature. Due to significant familial short stature and shortened arm span, SHOX gene analysis was performed and revealed patient is heterozygous for a novel SHOX gene mutation at nucleotide position c.582. This mutation is predicted to cause termination of the SHOX protein at codon 194, effectively causing haploinsufficiency. Six out of nine other siblings were later found to also be heterozygous for the same mutation. Growth hormone was initiated in all seven siblings upon diagnosis and they have demonstrated improved height SDS.

scholarly journals MON-113 The Effect of Body Mass Index on the Peak Growth Hormone Level After Growth Hormone Stimulation Test in Children with Short Stature

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Nayeong Lee ◽  
Wonkyoung Cho ◽  
Yoonji Lee ◽  
Seulki Kim ◽  
Seonhwa Lee ◽  
...  
Keyword(s):  
Body Mass Index ◽  
Growth Hormone ◽  
Regression Analysis ◽  
Short Stature ◽  
Body Mass ◽  
Multivariate Regression ◽  
Standard Deviation Score ◽  
Multivariate Regression Analysis ◽  
Stimulation Test ◽  
Peak Growth Hormone

Abstract Objective: The aim of this study is to evaluate the effect of body mass index (BMI) on peak growth hormone (GH) response after GH stimulation test in children with short stature. Methods: Data was obtained from retrospective review of medical records who visited the pediatric endocrinology at St. Vincent hospital of catholic university for short stature from January 2010 to June 2019. We studied 115 children (aged 3-17 years old) whose height was less than 3percentile for one’s age and sex and who underwent GH stimulation test {GH deficiency (GHD) = 47, Idiopathic short stature (ISS) = 68)}. Peak GH response was stimulated by dopamine (n=111), clonidine (n=7), glucagon (n=19), insulin (n=56) and arginine (n=32). Birth weight, parental height, chronologic age, bone age, height SDS (standard deviation score), weight SDS, BMI SDS hemoglobin, fT4, T3 TSH, cortisol, ACTH, GH, IGF-1 SDS, IGF-BP3 SDS and peak stimulated GH were analyzed. Results: In the characteristics of subject, weight SDS and BMI SDS in GHD group were increased than ISS group (p<0.000, p=0.000). Free T4 was decreased in GHD group than ISS group (p=0.012). In total group, BMI SDS was associated negatively with peak GH level stimulated by dopamine (r=-0.419, p<0.000), insulin (r=-0.271, p=0.044) and arginine (r=-0.368, p=0.038), but did not showed correlation with peak GH level stimulated by glucagon. In GHD group, BMI SDS showed negative correlation with peak GH level using dopamine (r=-0.356, p=0.015) and arginine (r=-0.509, p=0.022). In ISS group, BMI SDS was correlated negatively with peak GH using dopamine (r=-0.330, p=0.007). In multivariate regression analysis of GHD group, weight SDS and BMI SDS were the only two significant predictors of peak GH response in stimulation test stimulated by dopamine (ß=-0.576, p=0.015) and arginine (ß=-0.097, p=0.022). In ISS group, only mother’s height (ß=0.474, p=0.000) and TSH (ß=-2.251, p<0.000) were demonstrated statistically significant predictors of peak GH stimulated by dopamine in multivariate regression analysis. In case of using insulin as a stimulant in ISS group, there is nothing which has statistical significance as a predictor of peak GH response in multivariate regression analysis. Conclusion: BMI was associated negatively with peak GH response after GH stimulation test in children with short stature, especially in GHD group.

Growth Hormone Treatment for Short Stature in the USA, Germany and France: 15 Years of Surveillance in the Genetics and Neuroendocrinology of Short-Stature International Study (GeNeSIS)

2018 ◽  
Vol 90 (3) ◽  
pp. 169-180 ◽  
Author(s):  
Roland Pfäffle ◽  
Christof Land ◽  
Eckhard Schönau ◽  
Paul-Martin Holterhus ◽  
Judith L. Ross ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Short Stature ◽  
Standard Deviation Score ◽  
Measurement Data ◽  
International Study ◽  
Hormone Treatment ◽  
Height Velocity ◽  
Growth Disorders ◽  
Gh Treatment ◽  
The Usa

Background/Aims: To describe characteristics, auxological outcomes and safety in paediatric patients with growth disorders treated with growth hormone (GH), for cohorts from the USA, Germany and France enrolled in GeNeSIS, a post-authorisation surveillance programme. Methods: Diagnosis and biochemical measurement data were based on reporting from, and GH treatment was initiated at the discretion of, treating physicians. Auxological outcomes during the first 4 years of GH treatment and at near-adult height (NAH) were analysed. Serious and treatment-emergent adverse events were described. Results: Children in the USA (n = 9,810), Germany (n = 2,682) and France (n = 1,667) received GH (dose varied between countries), most commonly for GH deficiency. Across diagnostic groups and countries, mean height velocity standard deviation score (SDS) was > 0 and height SDS increased from baseline during the first 4 years of treatment, with greatest improvements during year 1. Most children achieved NAH within the normal range (height SDS >−2). No new or unexpected safety concerns were noted. Conclusion: GH treatment improved growth indices to a similar extent for patients in all three countries despite variations in GH doses. Data from these three countries, which together contributed > 60% of patients to GeNeSIS, indicated no new safety signals and the benefit-risk profile of GH remains unchanged.

scholarly journals Once-Weekly Administration of Sustained-Release Growth Hormone in Korean Prepubertal Children with Idiopathic Short Stature: A Randomized, Controlled Phase II Study

2018 ◽  
Vol 90 (1) ◽  
pp. 54-63 ◽  
Author(s):  
Jin Soon Hwang ◽  
Hae Sang Lee ◽  
Kee-Hyoung Lee ◽  
Han-Wook Yoo ◽  
Dae-Yeol Lee ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Sustained Release ◽  
Short Stature ◽  
Phase Ii ◽  
Phase Ii Study ◽  
Recombinant Human Growth Hormone ◽  
Standard Deviation Score ◽  
Idiopathic Short Stature ◽  
Height Velocity ◽  
Prepubertal Children

Background/Aims: To determine the optimal dose of LB03002, a sustained-release, once-weekly formulation of recombinant human growth hormone (rhGH), and to compare its efficacy and safety with daily rhGH in children with idiopathic short stature (ISS). Methods: This multicenter, randomized, open-label, phase II study included GH-naïve, prepubertal children with ISS, randomized to receive daily rhGH 0.37 mg/kg/week (control, n = 16), LB03002 0.5 mg/kg/week (n = 14), or LB03002 0.7 mg/kg/week (n = 16). The primary endpoint was height velocity (HV) change at week 26. Results: At week 26, the least square (LS) means for HV change (cm/year) with control, LB03002 0.5 mg/kg/week, and LB03002 0.7 mg/kg/week were 5.08, 3.65, and 4.38, and the LS means for the change in height standard deviation score were 0.65, 0.49, and 0.58, respectively. The lower bound of the 90% confidence interval for the difference between LB03002 0.7 mg/kg/week and the control in the LS mean for HV change (–1.72) satisfied the noninferiority margin (–1.75). Adverse events were generally mild and short-lived. Conclusion: A once-weekly regimen of LB03002 0.7 mg/kg demonstrated noninferiority to the daily regimen of rhGH 0.37 mg/kg/week in terms of HV increments. LB03002 was well tolerated and its safety profile was comparable with that of daily rhGH.

scholarly journals Real-World Treatment Patterns and Outcomes of Growth Hormone Treatment Among Children in Israel Over the Past Decade (2004–2015)

2021 ◽  
Vol 9 ◽  
Author(s):  
Tal Ben-Ari ◽  
Gabriel Chodick ◽  
Varda Shalev ◽  
Dalit Goldstein ◽  
Roy Gomez ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Short Stature ◽  
Real World ◽  
Standard Deviation Score ◽  
Healthcare Services ◽  
Treatment Patterns ◽  
Good Adherence ◽  
Gh Therapy ◽  
Gh Treatment

Objective: To assess a decade of growth hormone (GH) treatment patterns and outcomes in a real-world setting in Israel using a state-of-the-art computerized database.Methods: This large retrospective database study included 2,379 children initiating GH treatment in Maccabi Healthcare Services (between January 2004 and December 2014). Good adherence with therapy (proportion of days covered >80%) was assessed during follow-up.Results: At GH treatment initiation: 62.1% were boys; height standard deviation score (SDS) was −2.36 ± 0.65 (mean ± SD); age was 9.8 ± 3.1 years; and time from short stature diagnosis to first GH purchase was 4.8 ± 3.3 years. Mean treatment period was 3.5 ± 0.95 years; 79.4% of children were treated for more than 3 years. The two main indications for GH therapy were idiopathic short stature (ISS) (n = 1,615, 67.9%) and GH deficiency (GHD) (n = 611, 25.7%). Children in the highest socio-economic-status (SES) tertile comprised 61.3% of ISS and 59.7% of GHD. After 3 years, mean height gain SDS was 1.09 ± 0.91 for GHD and 0.96 ± 0.57 for ISS (p = 0.0004). Adult height (age 15 for girls and 17 for boys) was recorded for 624 patients (26.2%) with better outcomes for GHD than ISS (−1.0±0.82 vs. −1.28±0.93, respectively; p = 0.0002). Good adherence was achieved in 78.2% of the cohort during the first year and declined thereafter to 68.1% during the third year of the treatment.Conclusions: Children who initiate GH therapy are predominantly male, belong mainly to the upper SES, commence treatment a long period after initial recognition of short stature, and have suboptimal adherence. Appropriate referral, diagnosis, and follow-up care may result in better treatment outcomes with GH therapy.

scholarly journals Idiopathic short stature

2013 ◽  
Vol 141 (3-4) ◽  
pp. 256-261 ◽  
Author(s):  
Jovan Vlaski ◽  
Dragan Katanic ◽  
Jadranka Jovanovic-Privrodski ◽  
Ivana Kavecan ◽  
Ivana Vorgucin ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Standard Deviation ◽  
Short Stature ◽  
Standard Deviation Score ◽  
The Body ◽  
Idiopathic Short Stature ◽  
Hormone Deficiency ◽  
Growth Monitoring ◽  
Social Suffering ◽  
Deviation Score

Growth is a complex process and the basic characteristic of child- hood growth monitoring provides insight into the physiological and pathological events in the body. Statistically, the short stature means departure from the values of height for age and sex (in a particular environment), which is below -2 standard deviation score, or less than -2 standard deviation, i.e. below the third percentile. Advances in molecular genetics have contributed to the improvement of diagnostics in endocrinology. Analysis of patients? genotypes should not be performed before taking a classical history, detailed clinical examination and appropriate tests. In patients with idiopathic short stature specific causes are excluded, such as growth hormone deficiency, Turner syndrome, short stature due to low birth weight, intrauterine growth retardation, small for gestational age, dysmorphology syndromes and chronic childhood diseases. The exclusion of abovementioned conditions leaves a large number of children with short stature whose etiology includes patients with genetic short stature or familial short stature and those who are low in relation to genetic potential, and who could also have some unrecognized endocrine defect. Idiopathic short stature represents a short stature of unknown cause of heterogeneous etiology, and is characterized by a normal response of growth hormone during stimulation tests (>10 ng/ml or 20 mJ/l), without other disorders, of normal body mass and length at birth. In idiopathic short stature standard deviation score rates <-2.25 (-2 to -3) or <1.2 percentile. These are also criteria for the initiation of growth hormone therapy. In children with short stature there is also the presence of psychological and social suffering. Goals of treatment with growth hormone involve achieving normal height and normal growth rate during childhood.

Syndromic growth disorders

2011 ◽  
pp. 1095-1107
Author(s):  
Thomas Edouard ◽  
Maïthé Tauber
Keyword(s):  
Growth Hormone ◽  
Short Stature ◽  
Clinical Presentation ◽  
Pulmonary Stenosis ◽  
Standard Deviation Score ◽  
Growth Failure ◽  
Hormone Deficiency ◽  
High Resolution Analysis ◽  
Growth Hormone Insensitivity ◽  
Underlying Mechanisms

Short stature (SS) is defined as height less than the third percentile or below –2 standard deviation score (SDS) with reference to chronological age according to standard growth curves. Children are born small for gestational age (SGA) when their birth height and/or birth weight are below or equal to –2 SDS using standards such as Usher and McLean. In patients presenting with SS associated with abnormal physical features, malformations, or delayed development, a syndromic growth disorder should be considered. Whilst individually rare, there are many syndromes with short stature as a component—in the London Dysmorphology Database (Winter and Baraitser), there are 873 such syndromes, 175 of which are of prenatal onset. In these patients, malformations and/or sensorineural abnormalities should be systematically screened by complementary exams (skeletal X-rays, cardiac and abdominal ultrasound, complete eye and hearing evaluations). In some cases, these abnormalities could help in making the diagnosis (e.g. pulmonary stenosis suggestive of Noonan’s syndrome). Different chromosome disorders may present with SS. For this reason, chromosome studies, preferably high-resolution analysis, should be performed to search for chromosome abnormalities in these children. Specific gene analysis may be requested when a specific syndrome is suspected. In these syndromes, growth failure may be due to a wide variety of mechanisms, including growth hormone deficiency (GHD), growth hormone resistance (Laron syndrome, bone dysplasia) or in combination with nutritional issues with, in many, the underlying mechanisms still being unknown. A complete evaluation of growth hormone/IGF-1 axis is necessary in these children. There are many classifications of short stature, each with specific advantages and disadvantages. Indeed, syndromes with SS could be classified according to clinical presentation and in particular auxological and anthropometrical parameters (SS with normal prenatal growth, SS with intrauterine growth retardation, SS with obesity), or to pathophysiology (GHD or growth hormone insensitivity, bone disorders and idiopathic SS). Here, a classification based on clinical presentation is used. Those syndromes with SS that are most common and are often followed by paediatric endocrinologists namely Silver–Russell, Noonan’s, Turner’s and Prader–Willi syndromes will be reviewed, as well as some rarer syndromes.

GROWTH-PROMOTING THERAPIES MAY BE USEFUL IN SHORT STATURE PATIENTS WITH NONSPECIFIC SKELETAL ABNORMALITIES CAUSED BY ACAN HETEROZYGOUS MUTATIONS: SIX CHINESE CASES AND LITERATURE REVIEW

2020 ◽  
Vol 26 (11) ◽  
pp. 1255-1268
Author(s):  
Hanting Liang ◽  
Hui Miao ◽  
Hui Pan ◽  
Hongbo Yang ◽  
Fengying Gong ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Standard Deviation ◽  
Literature Review ◽  
Growth Hormone Deficiency ◽  
Short Stature ◽  
Standard Deviation Score ◽  
Hormone Deficiency ◽  
Novel Mutations ◽  
Deviation Score ◽  
Growth Promoting

Objective: There are numerous reasons for short stature, including mutations in osteochondral development genes. ACAN, one such osteochondral development gene in which heterozygous mutations can cause short stature, has attracted attention from researchers in recent years. Therefore, we analyzed six cases of short stature with heterozygous ACAN mutations and performed a literature review. Methods: Clinical information and blood samples from 6 probands and their family members were collected after consent forms were signed. Gene mutations in the probands were detected by whole-exome sequencing. Then, we searched the literature, performed statistical analyses, and summarized the characteristics of all reported cases. Results: We identified six novel mutations in ACAN: c.1411C>T, c.1817C>A, c.1762C>T, c.2266G>C, c.7469G>A, and c.1733-1G>A. In the literature, more than 200 affected individuals have been diagnosed genetically with a similar condition (height standard deviation score [SDS] −3.14 ± 1.15). Among affected individuals receiving growth-promoting treatment, their height before and after treatment was SDS −2.92 ± 1.07 versus SDS −2.14 ± 1.23 ( P<.001). As of July 1, 2019, a total of 57 heterozygous ACAN mutations causing nonsyndromic short stature had been reported, including the six novel mutations found in our study. Approximately half of these mutations can lead to protein truncation. Conclusion: This study used clinical and genetic means to examine the relationship between the ACAN gene and short stature. To some extent, clear diagnosis is difficult, since most of these affected individuals’ characteristics are not prominent. Growth-promoting therapies may be beneficial for increasing the height of affected patients. Abbreviations: AI = aromatase inhibitor; ECM = extracellular matrix; GnRHa = gonadotropin-releasing hormone analogue; IQR = interquartile range; MIM = Mendelian Inheritance in Man; PGHD = partial growth hormone deficiency; rhGH = recombinant human growth hormone; SDS = standard deviation score; SGA = small for gestational age; SGHD = severe growth hormone deficiency

NPR2 Variants Are Frequent among Children with Familiar Short Stature and Respond Well to Growth Hormone Therapy

2020 ◽  
Vol 105 (3) ◽  
pp. e746-e752 ◽  
Author(s):  
Lukas Plachy ◽  
Petra Dusatkova ◽  
Klara Maratova ◽  
Lenka Petruzelkova ◽  
Dana Zemkova ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Standard Deviation ◽  
Short Stature ◽  
Treatment Response ◽  
Growth Velocity ◽  
Final Height ◽  
Standard Deviation Score ◽  
Significant Proportion ◽  
Gene Variants ◽  
Gh Treatment

Abstract Context The C-type natriuretic peptide receptor encoded by the NPR2 gene is a paracrine regulator of the growth plate; heterozygous NPR2 variants cause short stature with possible presence of different signs of bone dysplasia. To date, the effect of growth hormone (GH) treatment has been described in a few individuals with NPR2 gene variants with inconsistent results. Objectives To identify NPR2 gene variants among children with familial short stature (FSS) and to describe their phenotype, including GH treatment response. Design, Settings and Patients Out of 747 patients with short stature treated with GH in a single center, 87 with FSS met the inclusion criteria (pretreatment height ≤ –2 standard deviation in both the patient and the shorter parent, unknown genetic etiology). Next-generation sequencing methods were performed to search for NPR2 gene variants. The results were evaluated using the American College of Medical Genetics and Genomics guidelines. The GH treatment response (growth velocity improvement and height standard deviation score development over the first 5 years of treatment) was evaluated. Results In 5/87 children (5.7%), a (likely) pathogenic variant in the NPR2 gene was identified (p.Ile558Thr [in 2], p.Arg205*, p.Arg557His, p.Ser603Thr). Two children had disproportionate short-limbed short stature, 1 a dysplastic 5th finger phalanx. The growth velocity in the first year of GH treatment accelerated by 3.6 to 4.2 cm/year; the height improved by 1.2 to 1.8 SD over 5 years of treatment. Conclusions NPR2 gene variants cause FSS in a significant proportion of children. Their GH treatment response is promising. Studies including final height data are necessary to assess the long-term efficacy of this therapy.

scholarly journals Growth Screening and Urban Deprivation

1995 ◽  
Vol 2 (3) ◽  
pp. 140-144 ◽  
Author(s):  
E White ◽  
A Wilson ◽  
S A Greene ◽  
W Berry ◽  
C McCowan ◽  
...  
Keyword(s):  
Standard Deviation ◽  
Short Stature ◽  
Social Deprivation ◽  
Standard Deviation Score ◽  
Primary School Children ◽  
British Society ◽  
Health Clinic ◽  
Height Standard Deviation Score ◽  
Deviation Score ◽  
Urban Deprivation

Objectives — To assess the effect of urban deprivation on childhood growth in a modern British society by analysing data from a regional growth survey, the Tayside growth study. Setting — The Tayside Region in Scotland, which has three districts with distinct socioeconomic status: Dundee (D, urban city), Angus (A, rural), and Perth (P, rural and county town). Subjects and methods — Height and weight of 23 046 children (>90% of the regional childhood population) were measured as part of a child health surveillance programme, by community health care workers at 3, 5, 7, 9, 11, and 14 years. Height standard deviation score (calculated against Tanner) and body mass index (BMI-weight (kg)/height (m)2) were calculated for each child by a central computer program; mean height standard deviation score and BMI standard deviation score were calculated for each measuring centre (school, health clinic). A deprivation score for each centre was calculated from the prevalence of single parent families; families with more than three children; unemployment rate; the number of social class V individuals; the percentage of council houses. Results — Mean height standard deviation score for Tayside was 0·11. An intra-regional difference was demonstrated: mean height standard deviation score (SD) D = 0·04 (1·0); A = 0·14 (1·1); P = 0·21 (1·1); P<0·002. There was a positive association between short stature and increasing social deprivation seen throughout Tayside (P<0·05), with a strong association in Dundee primary school children (r = 0·6; P<0·001). Analysis by district showed that the association was significant only above the age of 8 (P<0·004). There was no relation between BMI and social deprivation. Conclusions — In an industrialised developed society, urban deprivation appears to influence height mostly in late childhood, and this association should be taken into consideration in the clinical management of short stature. Height seems to be a better physical indicator of urban deprivation, and hence an index of childhood health, than BMI.

scholarly journals A SHOX géndeletio előfordulása idiopáthiás alacsonynövésben. Multicentrikus tanulmány

2017 ◽  
Vol 158 (34) ◽  
pp. 1351-1356 ◽  
Author(s):  
Anna Dávid ◽  
Henriett Butz ◽  
Zita Halász ◽  
Dóra Török ◽  
Gábor Nyirő ◽  
...  
Keyword(s):  
Short Stature ◽  
Turner Syndrome ◽  
Normal Karyotype ◽  
Idiopathic Short Stature ◽  
Female Dominance ◽  
Shox Gene ◽  
Gene Deficiency ◽  
Sitting Height ◽  
Arm Span ◽  
Gene Alterations

Abstract: Introduction: The isolated haploinsufficiency of the SHOX gene is one of the most common cause of short stature determined by monogenic mutations. The heterozygous deviation of the gene can be detected in 2–15% of patients with idiopathic short stature (ISS), in 50–90% of patients with Leri-Weill dyschondrosteosis syndrome (LWS), and in almost 100% of patients with Turner syndrome. Aim: The aim of our study was to evaluate the frequency of SHOX gene haploinsufficiency in children with ISS, LWS and in patients having Turner syndrome phenotype (TF), but normal karyotype, and to identify the dysmorphic signs characteristic for SHOX gene deficiency. Method: A total of 144 patients were included in the study. Multiplex Ligation-dependent Probe Amplification (MLPA) method was used to identify the SHOX gene haploinsufficiency. The relationships between clinical data (axiological parameters, skeletal disorders, dysmorphic signs) and genotype were analyzed by statistical methods. Results: 11 (7.6%) of the 144 patients showed SHOX gene deficiency with female dominance (8/11, 81% female). The SHOX positive patients had a significantly higher BMI (in 5/11 vs. 20/133 cases, p<0.02) and presented more frequent dysmorphic signs (9/11vs 62/133, p = 0.02). Madelung deformity of the upper limbs was also significantly more frequent among the SHOX positive patients (4/11, i.e. 36%, vs. 14/133, i.e. 10%, p = 0.0066). There were no statistically significant differences between the mean age, mean height and auxological measurements (sitting height/height, arm span/height) between the two groups of patients. Conclusions: The occurrence of SHOX gene haploinsufficiency observed in our population corresponds to the literature data. In SHOX positive patients, in addition to short stature, the dysmorphic signs have a positive predictive value for SHOX gene alterations. However, the SHOX deletion detected in a patient with idiopathic short stature without dysmorphic signs suggest that SHOX deletion analysis can be recommended in patients with ISS. Orv Hetil. 2017; 158(34): 1351–1356.

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