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[PMID]: 29524569
[Au] Autor:Slotkin TA; Skavicus S; Seidler FJ
[Ad] Address:Department of Pharmacology & Cancer Biology, Duke University Medical Center, Durham, NC, 27710, USA. Electronic address: t.slotkin@duke.edu.
[Ti] Title:Developmental Neurotoxicity Resulting from Pharmacotherapy of Preterm Labor, Modeled In Vitro: Terbutaline and Dexamethasone, Separately and Together.
[So] Source:Toxicology;, 2018 Mar 07.
[Is] ISSN:1879-3185
[Cp] Country of publication:Ireland
[La] Language:eng
[Ab] Abstract:Terbutaline and dexamethasone are used in the management of preterm labor, often for durations of treatment exceeding those recommended, and both have been implicated in increased risk of neurodevelopmental disorders. We used a variety of cell models to establish the critical stages at which neurodifferentiation is vulnerable to these agents and to determine whether combined exposures produce a worsened outcome. Terbutaline selectively promoted the initial emergence of glia from embryonic neural stem cells (NSCs). The target for terbutaline shifted with developmental stage: at later developmental stages modeled with C6 and PC12 cells, terbutaline had little effect on glial differentiation (C6 cells) but impaired the differentiation of neuronotypic PC12 cells into neurotransmitter phenotypes. In contrast to the specificity shown by terbutaline, dexamethasone affected both neuronal and glial differentiation at all stages, impairing the emergence of both cell types in NSCs but with a much greater impairment for glia. At later stages, dexamethasone promoted glial cell differentiation (C6 cells), while shifting neuronal cell differentiation so as to distort the balance of neurotransmitter phenotypes (PC12 cells). Finally, terbutaline and dexamethasone interacted synergistically at the level of late stage glial cell differentiation, with dexamethasone boosting the ability of terbutaline to enhance indices of glial cell growth and neurite formation while producing further decrements in glial cell numbers. Our results support the conclusion that terbutaline and dexamethasone are directly-acting neuroteratogens, and further indicate the potential for their combined use in preterm labor to worsen neurodevelopmental outcomes.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1803
[Cu] Class update date: 180310
[Lr] Last revision date:180310
[St] Status:Publisher

  2 / 92415 MEDLINE  
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[PMID]: 29507201
[Au] Autor:Garcia KE; Robinson EC; Alexopoulos D; Dierker DL; Glasser MF; Coalson TS; Ortinau CM; Rueckert D; Taber LA; Van Essen DC; Rogers CE; Smyser CD; Bayly PV
[Ad] Address:Department of Biomedical Engineering, Washington University in St. Louis, St. Louis, MO 63130; karaellspermann@gmail.com.
[Ti] Title:Dynamic patterns of cortical expansion during folding of the preterm human brain.
[So] Source:Proc Natl Acad Sci U S A;, 2018 Mar 05.
[Is] ISSN:1091-6490
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:During the third trimester of human brain development, the cerebral cortex undergoes dramatic surface expansion and folding. Physical models suggest that relatively rapid growth of the cortical gray matter helps drive this folding, and structural data suggest that growth may vary in both space (by region on the cortical surface) and time. In this study, we propose a unique method to estimate local growth from sequential cortical reconstructions. Using anatomically constrained multimodal surface matching (aMSM), we obtain accurate, physically guided point correspondence between younger and older cortical reconstructions of the same individual. From each pair of surfaces, we calculate continuous, smooth maps of cortical expansion with unprecedented precision. By considering 30 preterm infants scanned two to four times during the period of rapid cortical expansion (28-38 wk postmenstrual age), we observe significant regional differences in growth across the cortical surface that are consistent with the emergence of new folds. Furthermore, these growth patterns shift over the course of development, with noninjured subjects following a highly consistent trajectory. This information provides a detailed picture of dynamic changes in cortical growth, connecting what is known about patterns of development at the microscopic (cellular) and macroscopic (folding) scales. Since our method provides specific growth maps for individual brains, we are also able to detect alterations due to injury. This fully automated surface analysis, based on tools freely available to the brain-mapping community, may also serve as a useful approach for future studies of abnormal growth due to genetic disorders, injury, or other environmental variables.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1803
[Cu] Class update date: 180311
[Lr] Last revision date:180311
[St] Status:Publisher

  3 / 92415 MEDLINE  
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[PMID]: 29428545
[Au] Autor:Rogers S; Ramsay M; Blissett J
[Ad] Address:Centre for Research in Public Health & Community Care, University of Hertfordshire, UK.
[Ti] Title:The Montreal Children's Hospital Feeding Scale: Relationships with parental report of child eating behaviours and observed feeding interactions.
[So] Source:Appetite;125:201-209, 2018 Feb 09.
[Is] ISSN:1095-8304
[Cp] Country of publication:England
[La] Language:eng
[Ab] Abstract:Feeding problems are common, with implications for nutrition, growth and family stress, placing burden on primary care services. The Montreal Children's Hospital Feeding Scale (MCHFS) is a quick and reliable measure of feeding problems for clinical settings, but there is little examination of its relationship to commonly used research measures of parental feeding practice, child eating behaviour and observations of parent-infant interaction at mealtimes. We examined the relationships between the MCHFS, demographics and early feeding history, weight across the first year, parental report of feeding practices and child eating behaviours, and observations of maternal-infant feeding interaction at 1 year. The MCHFS, Comprehensive Feeding Practices Questionnaire (CFPQ) and Child Eating Behaviour Questionnaire (CEBQ) were completed by 69 mothers when their infants were 1-year-old (37 male, 32 female). Infant weight was measured at 1 week, 1 month, 6 months and 1 year. Mothers were observed feeding their infants at 1 year. The MCHFS was reliable (Cronbach's alpha = .90) and showed significant overlap with other measures of feeding and eating. Potential feeding problems were identified in 10 of the children (14%) reflecting similar rates in other community samples. Higher MCHFS scores were associated with lower birthweight and weight across the first year, greater satiety responsiveness, fussiness and slowness in eating, lower enjoyment of food and food responsiveness, and less observed infant food acceptance. Parents of infants with more feeding problems reported less encouragement of balance and variety in their children's diets. CONCLUSION: MCHFS showed good criterion validity with other parental report measures of eating and observations of mealtime interactions. MCHFS may be a useful tool for researching feeding problems in community samples.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1802
[Cu] Class update date: 180310
[Lr] Last revision date:180310
[St] Status:Publisher

  4 / 92415 MEDLINE  
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[PMID]: 29181510
[Au] Autor:Charif M; Nasca A; Thompson K; Gerber S; Makowski C; Mazaheri N; Bris C; Goudenège D; Legati A; Maroofian R; Shariati G; Lamantea E; Hopton S; Ardissone A; Moroni I; Giannotta M; Siegel C; Strom TM; Prokisch H; Vignal-Clermont C; Derrien S; Zanlonghi X; Kaplan J; Hamel CP; Leruez S; Procaccio V; Bonneau D; Reynier P; White FE; Hardy SA; Barbosa IA; Simpson MA; Vara R; Perdomo Trujillo Y; Galehdari H; Deshpande C; Haack TB; Rozet JM; Taylor RW; Ghezzi D; Amati-Bonneau P; Lenaers G
[Ad] Address:MitoLab Team, Unités Mixtes de Recherche Centre National de la Recherche Scientifique 6015-INSERM U1083, Institut MitoVasc, Angers University and Hospital, Angers, France.
[Ti] Title:Neurologic Phenotypes Associated With Mutations in RTN4IP1 (OPA10) in Children and Young Adults.
[So] Source:JAMA Neurol;75(1):105-113, 2018 Jan 01.
[Is] ISSN:2168-6157
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:Importance: Neurologic disorders with isolated symptoms or complex syndromes are relatively frequent among mitochondrial inherited diseases. Recessive RTN4IP1 gene mutations have been shown to cause isolated and syndromic optic neuropathies. Objective: To define the spectrum of clinical phenotypes associated with mutations in RTN4IP1 encoding a mitochondrial quinone oxidoreductase. Design, Setting, and Participants: This study involved 12 individuals from 11 families with severe central nervous system diseases and optic atrophy. Targeted and whole-exome sequencing were performed-at Hospital Angers (France), Institute of Neurology Milan (Italy), Imagine Institute Paris (France), Helmoltz Zentrum of Munich (Germany), and Beijing Genomics Institute (China)-to clarify the molecular diagnosis of patients. Each patient's neurologic, ophthalmologic, magnetic resonance imaging, and biochemical features were investigated. This study was conducted from May 1, 2014, to June 30, 2016. Main Outcomes and Measures: Recessive mutations in RTN4IP1 were identified. Clinical presentations ranged from isolated optic atrophy to severe encephalopathies. Results: Of the 12 individuals in the study, 6 (50%) were male and 6 (50%) were female. They ranged in age from 5 months to 32 years. Of the 11 families, 6 (5 of whom were consanguineous) had a member or members who presented isolated optic atrophy with the already reported p.Arg103His or the novel p.Ile362Phe, p.Met43Ile, and p.Tyr51Cys amino acid changes. The 5 other families had a member or members who presented severe neurologic syndromes with a common core of symptoms, including optic atrophy, seizure, intellectual disability, growth retardation, and elevated lactate levels. Additional clinical features of those affected were deafness, abnormalities on magnetic resonance images of the brain, stridor, and abnormal electroencephalographic patterns, all of which eventually led to death before age 3 years. In these patients, novel and very rare homozygous and compound heterozygous mutations were identified that led to the absence of the protein and complex I disassembly as well as mild mitochondrial network fragmentation. Conclusions and Relevance: A broad clinical spectrum of neurologic features, ranging from isolated optic atrophy to severe early-onset encephalopathies, is associated with RTN4IP1 biallelic mutations and should prompt RTN4IP1 screening in both syndromic neurologic presentations and nonsyndromic recessive optic neuropathies.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1711
[Cu] Class update date: 180311
[Lr] Last revision date:180311
[St] Status:In-Data-Review
[do] DOI:10.1001/jamaneurol.2017.2065

  5 / 92415 MEDLINE  
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[PMID]: 28467418
[Au] Autor:Khare S; Nick JA; Zhang Y; Galeano K; Butler B; Khoshbouei H; Rayaprolu S; Hathorn T; Ranum LPW; Smithson L; Golde TE; Paucar M; Morse R; Raff M; Simon J; Nordenskjöld M; Wirdefeldt K; Rincon-Limas DE; Lewis J; Kaczmarek LK; Fernandez-Funez P; Nick HS; Waters MF
[Ad] Address:Department of Neurology, University of Florida, Gainesville, FL, United States of America.
[Ti] Title:A KCNC3 mutation causes a neurodevelopmental, non-progressive SCA13 subtype associated with dominant negative effects and aberrant EGFR trafficking.
[So] Source:PLoS One;12(5):e0173565, 2017.
[Is] ISSN:1932-6203
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:The autosomal dominant spinocerebellar ataxias (SCAs) are a diverse group of neurological disorders anchored by the phenotypes of motor incoordination and cerebellar atrophy. Disease heterogeneity is appreciated through varying comorbidities: dysarthria, dysphagia, oculomotor and/or retinal abnormalities, motor neuron pathology, epilepsy, cognitive impairment, autonomic dysfunction, and psychiatric manifestations. Our study focuses on SCA13, which is caused by several allelic variants in the voltage-gated potassium channel KCNC3 (Kv3.3). We detail the clinical phenotype of four SCA13 kindreds that confirm causation of the KCNC3R423H allele. The heralding features demonstrate congenital onset with non-progressive, neurodevelopmental cerebellar hypoplasia and lifetime improvement in motor and cognitive function that implicate compensatory neural mechanisms. Targeted expression of human KCNC3R423H in Drosophila triggers aberrant wing veins, maldeveloped eyes, and fused ommatidia consistent with the neurodevelopmental presentation of patients. Furthermore, human KCNC3R423H expression in mammalian cells results in altered glycosylation and aberrant retention of the channel in anterograde and/or endosomal vesicles. Confirmation of the absence of plasma membrane targeting was based on the loss of current conductance in cells expressing the mutant channel. Mechanistically, genetic studies in Drosophila, along with cellular and biophysical studies in mammalian systems, demonstrate the dominant negative effect exerted by the mutant on the wild-type (WT) protein, which explains dominant inheritance. We demonstrate that ocular co-expression of KCNC3R423H with Drosophila epidermal growth factor receptor (dEgfr) results in striking rescue of the eye phenotype, whereas KCNC3R423H expression in mammalian cells results in aberrant intracellular retention of human epidermal growth factor receptor (EGFR). Together, these results indicate that the neurodevelopmental consequences of KCNC3R423H may be mediated through indirect effects on EGFR signaling in the developing cerebellum. Our results therefore confirm the KCNC3R423H allele as causative for SCA13, through a dominant negative effect on KCNC3WT and links with EGFR that account for dominant inheritance, congenital onset, and disease pathology.
[Mh] MeSH terms primary: Receptor, Epidermal Growth Factor/metabolism
Shaw Potassium Channels/genetics
Spinocerebellar Degenerations/genetics
[Mh] MeSH terms secundary: Animals
CHO Cells
Cricetinae
Cricetulus
Drosophila melanogaster
Female
Humans
Male
Pedigree
Protein Transport
[Pt] Publication type:JOURNAL ARTICLE
[Nm] Name of substance:0 (KCNC3 protein, human); 0 (Shaw Potassium Channels); EC 2.7.10.1 (Receptor, Epidermal Growth Factor)
[Em] Entry month:1709
[Cu] Class update date: 180311
[Lr] Last revision date:180311
[Js] Journal subset:IM
[Da] Date of entry for processing:170504
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0173565

  6 / 92415 MEDLINE  
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[PMID]: 29523633
[Au] Autor:Brue T; Amodru V; Castinetti F
[Ad] Address:T Brue, Endocrinology, Assistance Publique - Hôpitaux de Marseille (AP-HM) La Timone and Aix-Marseille University, Marseille, France thierry.brue@ap-hm.fr.
[Ti] Title:MANAGEMENT OF ENDOCRINE DISEASE: Management of Cushing's syndrome during Pregnancy: solved and unsolved questions.
[So] Source:Eur J Endocrinol;, 2018 Mar 09.
[Is] ISSN:1479-683X
[Cp] Country of publication:England
[La] Language:eng
[Ab] Abstract:With fewer than 200 reported cases, Cushing's syndrome (CS) in pregnancy remains a diagnostic and therapeutic challenge. In normal pregnancies, misleading signs may be observed such as striae or hypokalemia, while plasma cortisol and urinary free cortisol may rise up to 2-3-fold. While the dexamethasone suppression test is difficult to use, reference values for salivary cortisol appear valid. The predominant cause is adrenal adenoma (sometimes without decreased ACTH), rather than Cushing's disease. There are considerable imaging pitfalls in Cushing's disease. Aberrant receptors may, in rare cases, lead to increased cortisol production during pregnancy in response to HCG, LHRH, glucagon, vasopressin or after a meal. Adrenocortical carcinoma (ACC) is rare and has poor prognosis. Active CS during pregnancy is associated with a high rate of maternal complications: hypertension or preeclampsia, diabetes, fractures; more rarely, cardiac failure, psychiatric disorders, infection and maternal death. Increased fetal morbidity includes prematurity, intrauterine growth retardation, and less prevalently stillbirth, spontaneous abortion, intrauterine death, and hypoadrenalism. Therapy is also challenging. Milder cases can be managed conservatively by controlling comorbidities. Pituitary or adrenal surgery should ideally be performed during the second trimester and patients should then be treated for adrenal insufficiency. Experience with anticortisolic drugs is limited. Metyrapone was found to allow control of hypercortisolism, with a risk of worsening hypertension. Cabergoline may be an alternative option. The use of other drugs is not advised because of potential teratogenicity and/or lack of information. Non-hormonal (mechanical) contraception is recommended until sustained biological remission is obtained.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1803
[Cu] Class update date: 180310
[Lr] Last revision date:180310
[St] Status:Publisher

  7 / 92415 MEDLINE  
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[PMID]: 29523380
[Au] Autor:Simermann M; Rothenburger S; Auburtin B; Hascoët JM
[Ad] Address:Neonatology Departement, maternité régionale CHRU Nancy, rue du Morvan, 54511 Vandoeuvre-lès-Nancy, France. Electronic address: m.simermann@chru-nancy.fr.
[Ti] Title:Outcome of children born after pregnancy denial.
[So] Source:Arch Pediatr;, 2018 Mar 07.
[Is] ISSN:1769-664X
[Cp] Country of publication:France
[La] Language:eng
[Ab] Abstract:INTRODUCTION: Denial of pregnancy remains a phenomenon little known to healthcare professionals. Yet its repercussions are far from negligible. The aim of this study was to assess whether denial of pregnancy has an impact on the infant's development. PATIENTS AND METHOD: This prospective study included 51 full-term infants born in Nancy Regional Maternity Hospital between 1 January 2009 and 30 June 2015. In this study, the development of the children was followed longitudinally. We collected data during the neonatal period, at 9months, and at 2years of age from the infants' file and standardized medical certificates, and current data through a telephone questionnaire. Three fundamental aspects of the infants' development were analyzed: height and weight growth, psychomotor development, and the existence of pathologies. Given that this was a preliminary study aiming at exploring facts, no statistical tests were carried out. RESULTS: The rate of denial of pregnancy was one birth in 300 during the study period. These infants showed proportional intrauterine growth restriction, which leveled out later, with their height and weight growth normal by month 9. The full-term perinatal mortality rate was 5%. The infants showed no sign of increased morbidity; 20% of them presented with delayed psychomotor development at 9months of age, with an increased impact as they grew older. The rate reached 30% after 24months, half of which were language disorders. CONCLUSION: The results of this preliminary study point out the need for thorough monitoring of these infants throughout infancy.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1803
[Cu] Class update date: 180310
[Lr] Last revision date:180310
[St] Status:Publisher

  8 / 92415 MEDLINE  
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[PMID]: 29523276
[Au] Autor:Chan SL; Rana S; Chinthala S; Salahuddin S; Yeo KJ
[Ad] Address:Department of Pathology, The University of Chicago, Chicago, IL, United States.
[Ti] Title:Analytical validation of soluble fms-like tyrosine and placental growth factor assays on B·R·A·H·M·S KRYPTOR Compact Plus automated immunoassay platform.
[So] Source:Pregnancy Hypertens;11:66-70, 2018 Jan.
[Is] ISSN:2210-7797
[Cp] Country of publication:Netherlands
[La] Language:eng
[Ab] Abstract:BACKGROUND: Preeclampsia is one of the leading hypertensive disorders of pregnancy. Angiogenic biomarkers such as anti-angiogenic factor soluble fms-like tyrosine kinase 1 (sFlt1) and pro-angiogenic factor placental growth factor (PlGF) are involved in the pathophysiology of preeclampsia. OBJECTIVE: The aim of this study is to validate the analytical performance of sFlt1 and PlGF on the B·R·A·H·M·S KRYPTOR Compact Plus (ThermoFisher Scientific). STUDY DESIGN: We examined K -EDTA plasma samples from 50 patients on B·R·A·H·M·S KRYPTOR Compact Plus, an automated immunoassay platform. QC materials were used to assess intra- and inter-precision of the assay. Lower limit of quantitation and interference studies were determined using pooled patient plasma. RESULTS: The sFlt1 and PlGF assays demonstrated an analytical measuring range of 90-69,000 pg/mL and 11-7000 pg/mL, respectively (r > 0.99). Lower limit of quantitation (20% CV) was interpolated to be 35 pg/mL for sFlt1 and 10 pg/mL for PlGF. Total precision for both assay displayed CVs of <10%. Interference studies showed that both assays were not significantly affected by hemolysis up to an H-index of 1100 for sFlt1 and 300 for PlGF; L- and I-index of 800 and 80 respectively for both assays. The Passing-Bablok regression analysis for sFlt1/PlGF yielded an equation of y = 1.05x + 0.02, and the Bland Altman analysis showed an average bias of 0.84. CONCLUSION: Plasma levels of sFlt1 and PlGF measured on the B·R·A·H·M·S KRYPTOR Compact Plus platform demonstrate excellent analytical performance and are acceptable as clinical grade assays.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1803
[Cu] Class update date: 180310
[Lr] Last revision date:180310
[St] Status:In-Process

  9 / 92415 MEDLINE  
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[PMID]: 29523275
[Au] Autor:Cheng YKY; Law LW; Leung TY; Chan OK; Sahota DS
[Ad] Address:Department of Obstetrics and Gynaecology, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong Special Administrative Region.
[Ti] Title:Soluble fms-like tyrosine kinase-1, placental growth factor and their ratio as a predictor for pre-eclampsia in East Asians.
[So] Source:Pregnancy Hypertens;11:61-65, 2018 Jan.
[Is] ISSN:2210-7797
[Cp] Country of publication:Netherlands
[La] Language:eng
[Ab] Abstract:OBJECTIVE: To assess the clinical utility of the sFlt-1:PlGF ratio rule-in/rule-out pre-eclampsia either directly or after correcting each marker for gestation and maternal weight. METHODS: This was a prospective cohort study. sFlt-1, PlGF were measured in 965 women randomized to undergo a single blood withdraw between 20 and 39 weeks of gestation. sFlt-1, PlGF and the sFlt-1:PlGF ratio temporal relationship was determined. sFlt-1 and PlGF were converted to multiples of the expected gestational median (MoM) and adjusted for maternal weight. The 90th centile of the adjusted sFlt-1MoM:PlGFMoM ratio was determined. Clinical utility of the sFlt-1:PlGF ratio (≥38) to rule in/rule-out pre-eclampsia (PE) after 20 weeks of gestation versus that of the sFlt-1MoM:PlGFMoM 90th percentile was assessed in 81 women admitted for management of antenatal hypertension. RESULTS: The sFlt-1:PlGF ratio had quadratic relationship with gestation whereas the sFlt-1MoM:PlGFMoM ratio log distribution that was Gaussian with a mean of zero and a standard deviation of 0.85 with a 90th percentile equal to 1.08. Thirty-four (42%) of the 81 women admitted for management of their antenatal hypertension had PE, 26 (76.4%) had a sFlt-1:PlGF ratio ≥ 38. Four of the remaining 8 PE affected pregnancies with sFlt-1:PlGF ratio <38 delivered within 7 days, 3 were preterm. Two of the 3 preterm PE pregnancies had sFlt-1MoM:PlGFMoM exceeding 90th percentile. CONCLUSION: The relative level of the sFlt-1 to PlGF carries prognostic value. A sFlt-1MoM:PlGFMoM ratio exceeding the 90th centile resulted in additional detection of pregnancies which developed PE compared to the conventional sFlt-1:PlGF ratio.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1803
[Cu] Class update date: 180310
[Lr] Last revision date:180310
[St] Status:In-Process

  10 / 92415 MEDLINE  
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[PMID]: 29523172
[Au] Autor:Maini I; Ivanovski I; Djuric O; Caraffi SG; Errichiello E; Marinelli M; Franchi F; Bizzarri V; Rosato S; Pollazzon M; Gelmini C; Malacarne M; Fusco C; Gargano G; Bernasconi S; Zuffardi O; Garavelli L
[Ad] Address:Clinical Genetics Unit, Maternal and Child Health Department, AUSL-IRCCS of Reggio Emilia, Reggio Emilia, Italy.
[Ti] Title:Prematurity, ventricular septal defect and dysmorphisms are independent predictors of pathogenic copy number variants: a retrospective study on array-CGH results and phenotypical features of 293 children with neurodevelopmental disorders and/or multiple congenital anomalies.
[So] Source:Ital J Pediatr;44(1):34, 2018 Mar 09.
[Is] ISSN:1824-7288
[Cp] Country of publication:England
[La] Language:eng
[Ab] Abstract:BACKGROUND: Since 2010, array-CGH (aCGH) has been the first-tier test in the diagnostic approach of children with neurodevelopmental disorders (NDD) or multiple congenital anomalies (MCA) of unknown origin. Its broad application led to the detection of numerous variants of uncertain clinical significance (VOUS). How to appropriately interpret aCGH results represents a challenge for the clinician. METHOD: We present a retrospective study on 293 patients with age range 1 month - 29 years (median 7 years) with NDD and/or MCA and/or dysmorphisms, investigated through aCGH between 2005 and 2016. The aim of the study was to analyze clinical and molecular cytogenetic data in order to identify what elements could be useful to interpret unknown or poorly described aberrations. Comparison of phenotype and cytogenetic characteristics through univariate analysis and multivariate logistic regression was performed. RESULTS: Copy number variations (CNVs) with a frequency < 1% were detected in 225 patients of the total sample, while 68 patients presented only variants with higher frequency (heterozygous deletions or amplification) and were considered to have negative aCGH. Proved pathogenic CNVs were detected in 70 patients (20.6%). Delayed psychomotor development, intellectual disability, intrauterine growth retardation (IUGR), prematurity, congenital heart disease, cerebral malformations and dysmorphisms correlated to reported pathogenic CNVs. Prematurity, ventricular septal defect and dysmorphisms remained significant predictors of pathogenic CNVs in the multivariate logistic model whereas abnormal EEG and limb dysmorphisms were mainly detected in the group with likely pathogenic VOUS. A flow-chart regarding the care for patients with NDD and/or MCA and/or dysmorphisms and the interpretation of aCGH has been made on the basis of the data inferred from this study and literature. CONCLUSION: Our work contributes to make the investigative process of CNVs more informative and suggests possible directions in aCGH interpretation and phenotype correlation.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1803
[Cu] Class update date: 180310
[Lr] Last revision date:180310
[St] Status:In-Process
[do] DOI:10.1186/s13052-018-0467-z


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