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154 results on '"Haghshenas S"'

6. An exploratory view of water quality and sediment characteristics in Musa Estuary, the Persian Gulf

Author

Haghshenas, S. Mostafa

Subjects
Physics - Atmospheric and Oceanic Physics
Abstract

The results of mentioned physicochemical and biological analysis show that in more polluted sampling points, the number of resistance benthos (Bivalves) are more than other points of the study area. Heavy metal concentration in sediment is between 10 to 1000 times more than water samples especially for Arsenic, Mercury, and Vanadium. Dissolved Oxygen is acceptable all over the study area (more than 4 mg/L) based on environmental quality standards for dissolved oxygen which present the range of 2-9 mg/l for sensitive aquatic lives to less sensitive ones. However the presence of chemicals causes increase in the value of Chemical Oxygen Demand (around 500 to 1000 mg/L) and consequent decrease in water purification ability Nutrient uptake capacity which shown as the ratio of Nitrogen to phosphorus is appropriate (around 6) in parts of Musa estuary with more than 3 meters depth . The study area is a semi-closed tide-dominant water body with shallow depth, in comparison to the oceans. A 2-D modelling is applied to simulate current speed and direction. The results of this modelling shows except in the creeks, we have relatively suitable circulation of water in the estuary and current speed may exceed 0.8 m/s. It means Musa estuary is not a dead zone and in some parts which have enough water circulation and nutrient uptake for aquatic life, but huge amount of heavy metal (especially Mercury) in the sediment and water samples, indicates that all aquatic bodies overwhelmed by dangerous heavy metals.

Published
2020

13. DNA methylation episignature and comparative epigenomic profiling for Pitt-Hopkins syndrome caused by TCF4 variants

Author

Laan, L. van der, Lauffer, P., Rooney, K., Silva, A., Haghshenas, S., Relator, Raissa, Kleefstra, T., Bon, B.W.M. van, Vitobello, A., Menke, Leonie A., Laan, L. van der, Lauffer, P., Rooney, K., Silva, A., Haghshenas, S., Relator, Raissa, Kleefstra, T., Bon, B.W.M. van, Vitobello, A., and Menke, Leonie A.

Abstract

Contains fulltext : 307198.pdf (Publisher’s version ) (Open Access)

Published
2024

19. Novel diagnostic DNA methylation episignatures expand and refine the epigenetic landscapes of Mendelian disorders.

Author

Levy, MA, McConkey, H, Kerkhof, J, Barat-Houari, M, Bargiacchi, S, Biamino, E, Bralo, MP, Cappuccio, G, Ciolfi, A, Clarke, A, DuPont, BR, Elting, MW, Faivre, L, Fee, T, Fletcher, RS, Cherik, F, Foroutan, A, Friez, MJ, Gervasini, C, Haghshenas, S, Hilton, BA, Jenkins, Z, Kaur, S, Lewis, S, Louie, RJ, Maitz, S, Milani, D, Morgan, AT, Oegema, R, Østergaard, E, Pallares, NR, Piccione, M, Pizzi, S, Plomp, AS, Poulton, C, Reilly, J, Relator, R, Rius, R, Robertson, S, Rooney, K, Rousseau, J, Santen, GWE, Santos-Simarro, F, Schijns, J, Squeo, GM, St John, M, Thauvin-Robinet, C, Traficante, G, van der Sluijs, PJ, Vergano, SA, Vos, N, Walden, KK, Azmanov, D, Balci, T, Banka, S, Gecz, J, Henneman, P, Lee, JA, Mannens, MMAM, Roscioli, T, Siu, V, Amor, DJ, Baynam, G, Bend, EG, Boycott, K, Brunetti-Pierri, N, Campeau, PM, Christodoulou, J, Dyment, D, Esber, N, Fahrner, JA, Fleming, MD, Genevieve, D, Kerrnohan, KD, McNeill, A, Menke, LA, Merla, G, Prontera, P, Rockman-Greenberg, C, Schwartz, C, Skinner, SA, Stevenson, RE, Vitobello, A, Tartaglia, M, Alders, M, Tedder, ML, Sadikovic, B, Levy, MA, McConkey, H, Kerkhof, J, Barat-Houari, M, Bargiacchi, S, Biamino, E, Bralo, MP, Cappuccio, G, Ciolfi, A, Clarke, A, DuPont, BR, Elting, MW, Faivre, L, Fee, T, Fletcher, RS, Cherik, F, Foroutan, A, Friez, MJ, Gervasini, C, Haghshenas, S, Hilton, BA, Jenkins, Z, Kaur, S, Lewis, S, Louie, RJ, Maitz, S, Milani, D, Morgan, AT, Oegema, R, Østergaard, E, Pallares, NR, Piccione, M, Pizzi, S, Plomp, AS, Poulton, C, Reilly, J, Relator, R, Rius, R, Robertson, S, Rooney, K, Rousseau, J, Santen, GWE, Santos-Simarro, F, Schijns, J, Squeo, GM, St John, M, Thauvin-Robinet, C, Traficante, G, van der Sluijs, PJ, Vergano, SA, Vos, N, Walden, KK, Azmanov, D, Balci, T, Banka, S, Gecz, J, Henneman, P, Lee, JA, Mannens, MMAM, Roscioli, T, Siu, V, Amor, DJ, Baynam, G, Bend, EG, Boycott, K, Brunetti-Pierri, N, Campeau, PM, Christodoulou, J, Dyment, D, Esber, N, Fahrner, JA, Fleming, MD, Genevieve, D, Kerrnohan, KD, McNeill, A, Menke, LA, Merla, G, Prontera, P, Rockman-Greenberg, C, Schwartz, C, Skinner, SA, Stevenson, RE, Vitobello, A, Tartaglia, M, Alders, M, Tedder, ML, and Sadikovic, B

Abstract

Overlapping clinical phenotypes and an expanding breadth and complexity of genomic associations are a growing challenge in the diagnosis and clinical management of Mendelian disorders. The functional consequences and clinical impacts of genomic variation may involve unique, disorder-specific, genomic DNA methylation episignatures. In this study, we describe 19 novel episignature disorders and compare the findings alongside 38 previously established episignatures for a total of 57 episignatures associated with 65 genetic syndromes. We demonstrate increasing resolution and specificity ranging from protein complex, gene, sub-gene, protein domain, and even single nucleotide-level Mendelian episignatures. We show the power of multiclass modeling to develop highly accurate and disease-specific diagnostic classifiers. This study significantly expands the number and spectrum of disorders with detectable DNA methylation episignatures, improves the clinical diagnostic capabilities through the resolution of unsolved cases and the reclassification of variants of unknown clinical significance, and provides further insight into the molecular etiology of Mendelian conditions.

Published
2022

20. DNA Methylation Signature for JARID2-Neurodevelopmental Syndrome

Author

Verberne, E.A., Laan, L. van der, Haghshenas, S., Rooney, K., Levy, M.A., Alders, M., Koolen, D.A., Pfundt, R.P., Henneman, Peter, Haelst, Mieke M. van, Verberne, E.A., Laan, L. van der, Haghshenas, S., Rooney, K., Levy, M.A., Alders, M., Koolen, D.A., Pfundt, R.P., Henneman, Peter, and Haelst, Mieke M. van

Abstract

Contains fulltext : 253042.pdf (Publisher’s version ) (Open Access)

Published
2022

22. Oxybenzone contamination from sunscreen pollution and its ecological threat to Hanauma Bay, Oahu, Hawaii, U.S.A.

Author

Downs, C.A., primary, Bishop, Elizabeth, additional, Diaz-Cruz, M. Silvia, additional, Haghshenas, S. Abbas, additional, Stien, Didier, additional, Rodrigues, Alice M.S., additional, Woodley, Cheryl M., additional, Sunyer-Caldú, Adrià, additional, Doust, Shadan Nasseri, additional, Espero, William, additional, Ward, Gene, additional, Farhangmehr, Aref, additional, Tabatabaee Samimi, S. Maryam, additional, Risk, Michael J., additional, Lebaron, Philippe, additional, and DiNardo, Joseph C., additional

Published
2022
Full Text
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24. Delineating the molecular and phenotypic spectrum of the SETD1B-related syndrome

Author

Weerts, M.J.A., Lanko, K., Guzmán-Vega, F.J., Jackson, A., Ramakrishnan, R., Cardona-Londoño, K.J., Peña-Guerra, K.A., Bever, Y. Van, Paassen, B.W. van, Kievit, A., Slegtenhorst, M. van, Allen, N.M., Kehoe, C.M., Robinson, H.K., Pang, L., Banu, S.H., Zaman, M., Efthymiou, S., Houlden, H., Järvelä, I., Lauronen, L., Määttä, T., Schrauwen, I., Leal, S.M., Ruivenkamp, C.A.L., Barge-Schaapveld, D., Peeters-Scholte, C., Galehdari, H., Mazaheri, N., Sisodiya, S.M., Harrison, V., Sun, A., Thies, J., Pedroza, L.A., Lara-Taranchenko, Y., Chinn, I.K., Lupski, J.R., Garza-Flores, A., McGlothlin, J., Yang, L., Huang, S., Wang, X, Jewett, T., Rosso, G., Lin, X., Mohammed, S, Merritt, J.L., 2nd, Mirzaa, G.M., Timms, A.E., Scheck, J., Elting, M.W., Polstra, A.M., Schenck, L., Ruzhnikov, M.R.Z., Vetro, A., Montomoli, M., Guerrini, R., Koboldt, D.C., Mosher, T.M., Pastore, M.T., McBride, K.L., Peng, J., Pan, Z., Willemsen, M.H., Koning, S. de, Turnpenny, P.D., Vries, B.B. de, Gilissen, C., Pfundt, R.P., Lees, M., Braddock, S.R., Klemp, K.C., Vansenne, F., Gijn, M.E. van, Quindipan, C., Deardorff, M.A., Hamm, J.A., Putnam, A.M., Baud, R., Walsh, L., Lynch, S.A., Baptista, J., Person, R.E., Monaghan, K.G., Crunk, A., Keller-Ramey, J., Reich, A., Elloumi, H.Z., Alders, M., Kerkhof, J., McConkey, H., Haghshenas, S., Maroofian, R., Sadikovic, B., Banka, S., Arold, Stefan T., Barakat, T.S., Weerts, M.J.A., Lanko, K., Guzmán-Vega, F.J., Jackson, A., Ramakrishnan, R., Cardona-Londoño, K.J., Peña-Guerra, K.A., Bever, Y. Van, Paassen, B.W. van, Kievit, A., Slegtenhorst, M. van, Allen, N.M., Kehoe, C.M., Robinson, H.K., Pang, L., Banu, S.H., Zaman, M., Efthymiou, S., Houlden, H., Järvelä, I., Lauronen, L., Määttä, T., Schrauwen, I., Leal, S.M., Ruivenkamp, C.A.L., Barge-Schaapveld, D., Peeters-Scholte, C., Galehdari, H., Mazaheri, N., Sisodiya, S.M., Harrison, V., Sun, A., Thies, J., Pedroza, L.A., Lara-Taranchenko, Y., Chinn, I.K., Lupski, J.R., Garza-Flores, A., McGlothlin, J., Yang, L., Huang, S., Wang, X, Jewett, T., Rosso, G., Lin, X., Mohammed, S, Merritt, J.L., 2nd, Mirzaa, G.M., Timms, A.E., Scheck, J., Elting, M.W., Polstra, A.M., Schenck, L., Ruzhnikov, M.R.Z., Vetro, A., Montomoli, M., Guerrini, R., Koboldt, D.C., Mosher, T.M., Pastore, M.T., McBride, K.L., Peng, J., Pan, Z., Willemsen, M.H., Koning, S. de, Turnpenny, P.D., Vries, B.B. de, Gilissen, C., Pfundt, R.P., Lees, M., Braddock, S.R., Klemp, K.C., Vansenne, F., Gijn, M.E. van, Quindipan, C., Deardorff, M.A., Hamm, J.A., Putnam, A.M., Baud, R., Walsh, L., Lynch, S.A., Baptista, J., Person, R.E., Monaghan, K.G., Crunk, A., Keller-Ramey, J., Reich, A., Elloumi, H.Z., Alders, M., Kerkhof, J., McConkey, H., Haghshenas, S., Maroofian, R., Sadikovic, B., Banka, S., Arold, Stefan T., and Barakat, T.S.

Abstract

Contains fulltext : 243955.pdf (Publisher’s version ) (Open Access), PURPOSE: Pathogenic variants in SETD1B have been associated with a syndromic neurodevelopmental disorder including intellectual disability, language delay, and seizures. To date, clinical features have been described for 11 patients with (likely) pathogenic SETD1B sequence variants. This study aims to further delineate the spectrum of the SETD1B-related syndrome based on characterizing an expanded patient cohort. METHODS: We perform an in-depth clinical characterization of a cohort of 36 unpublished individuals with SETD1B sequence variants, describing their molecular and phenotypic spectrum. Selected variants were functionally tested using in vitro and genome-wide methylation assays. RESULTS: Our data present evidence for a loss-of-function mechanism of SETD1B variants, resulting in a core clinical phenotype of global developmental delay, language delay including regression, intellectual disability, autism and other behavioral issues, and variable epilepsy phenotypes. Developmental delay appeared to precede seizure onset, suggesting SETD1B dysfunction impacts physiological neurodevelopment even in the absence of epileptic activity. Males are significantly overrepresented and more severely affected, and we speculate that sex-linked traits could affect susceptibility to penetrance and the clinical spectrum of SETD1B variants. CONCLUSION: Insights from this extensive cohort will facilitate the counseling regarding the molecular and phenotypic landscape of newly diagnosed patients with the SETD1B-related syndrome.

Published
2021

25. Oxybenzone contamination from sunscreen pollution and its ecological threat to Hanauma Bay, Oahu, Hawaii, U.S.A

Author

0000-0002-8486-9816, 0000-0001-7532-2934, 0000-0001-5134-1196, 0000-0002-2514-4516, 0000-0001-8823-9814, Downs, C. A., Bishop, Elizabeth, Díaz-Cruz, M. Silvia, Haghshenas, S. Abbas, Stien, Didier, Rodrigues, Alice M. S., Woodley, Cheryl M., Sunyer-Caldú, Adrià, Doust, Shadan Nasseri, Espero, William, Ward, Gene, Farhangmehr, Aref, Tabatabaee Samimi, S. Maryam, Risk, Michael J., Lebaron, Philippe, DiNardo, Joseph C., 0000-0002-8486-9816, 0000-0001-7532-2934, 0000-0001-5134-1196, 0000-0002-2514-4516, 0000-0001-8823-9814, Downs, C. A., Bishop, Elizabeth, Díaz-Cruz, M. Silvia, Haghshenas, S. Abbas, Stien, Didier, Rodrigues, Alice M. S., Woodley, Cheryl M., Sunyer-Caldú, Adrià, Doust, Shadan Nasseri, Espero, William, Ward, Gene, Farhangmehr, Aref, Tabatabaee Samimi, S. Maryam, Risk, Michael J., Lebaron, Philippe, and DiNardo, Joseph C.

Abstract

Hanauma Bay is a 101-acre bay created by the partial collapse of a volcanic cone and once supported a vibrant coral reef system. It is the most popular swimming area in the Hawaiian Islands and has been reported to have averaged between 2.8 and 3.5 million visitors a year between the 1980s and the 2010s, with visitors averaging between 3000-4000 a day and peaking around 10,000-13,000 per day. Concentrations of oxybenzone and other common UV filters were measured in subsurface water samples and in sands from the beach-shower areas in Hanauma Bay. Results demonstrate that beach showers also can be a source of sunscreen environmental contamination. Hydrodynamic modeling indicates that oxybenzone contamination within Hanauma Bay's waters could be retained between 14 and 50 h from a single release event period. Focusing on only oxybenzone, two different Hazard and Risk Assessment analyses were conducted to determine the danger of oxybenzone to Hanauma Bay's coral reef system. Results indicate that oxybenzone contamination poses a significant threat to the wildlife of Hanauma Bay. To recover Hanauma Bay's natural resources to a healthy condition and to satisfactorily conserve its coral reef and sea grass habitats, effective tourism management policies need to be implemented that mitigate the threat of sunscreen pollution.

Published
2021

38. Evaluation of Demographic Characteristics and Attitudes about Traditional Medicine among Patients Referred to a Clinic.

Author

Hozni, A., Azmiyan Moghadam, F., Yeganeh, M. R., and Haghshenas, S.

Abstract

Introduction: Traditional medicine is a set of skills and knowledge and practice based on theories and experiences indigenous to different cultures used for the prevention, diagnosis and treatment of mental and physical diseases. Given the differences in attitudes and demographic characteristics of the population in traditional medicine, guiding public opinion toward this kind of practice is important. Objective: To determine the demographic characteristics and attitudes about traditional medicine among patients in Ghaem clinics in Rasht, northern Iran. Materials and Methods: This study was a descriptive cross - sectional study on 132 patients in Ghaem clinics in Rasht that is specialist center for some traditional medications (i.e., bloodletting, leeches and bloodletting therapy). The study was performed during the first quarter of 2013.Convenience sampling and the reasercher questionnaire consisting of 33 items with 5 option Likert scale were used to collect data. Cronbach's alpha reliability coefficient was calculated 88.Content validity was confirmed by the university teachers. Statistical analyses including descriptive statistics and analysis Kolmogorov Asprynf test, Mann-Whitney and Kruskal-Wallis tests were performed using the spss software version 21. Results: The most frequent reason of patients referred to the clinic was their rheumatic and joint pains(25/8)%, headache(18/5%)and sinusitis and Hypertension(8/9%). Their knowledge of traditional medicine and health benefits were from reading books and internet(40.2 %),the experiences of others(36.5%), newspapers, television and the mass media(1.5%),and friends' recommendations (29%). In general, a positive attitude towards the traditional medicine was observed with a mean score of approximately (3/9) of 5criteria. Most clients asked for better promotion of traditional medicine on TV and radio, and arranging training classes. Also, 70% of clients say that lower expenses, better treatment with no uncomplications and shorter treatment course were the main reasons that they consult the traditional centers. Conclusion: The Ministry of Health and policymakers should inform, and supervise the centers offering traditional medicine, to pave the way for the popularity of this precious medical legacy. The inclusion of courses in medical and pharmaceutical fields is highly desirable for this end. Also, the more publicity through the mass media, especially television, and short term courses can be useful in this context. Conflict of interest: non declared [ABSTRACT FROM AUTHOR]

Published
2015

40. Chapter 26: An integrated hydrodynamic model on muddy coasts.

Author

Soltanpour, Mohsen, Haghshenas, S. Abbas, and Shibayama, Tomoya

Abstract

A numerical cross-shore model to simulate two features of wave-mud interaction on fine-grained shore profiles, i.e. fluidization of mud layer and wave height attenuation, is presented. The analytical model of Foda et al. (1993) is used to determine the fluidized depth of mud layer. The wave height transformation is computed from the energy flux conservation law combining the effects of mud bed, shoaling and wave breaking. The rheological constitutive equations of visco-elastic (VE) material are used for numerical simulation of fluid mud behavior. A preliminary application of the model shows its capability to predict wave height transformation along soft muddy profiles. [ABSTRACT FROM AUTHOR]

Published
2007

41. A Prospective Study on the Relationship between Sports Injuries and some of the Physical Fitness Factors in Soccer Players

Author

daneshmandi hassan and Haghshenas Soheil

Subjects
Muscular strength, Flexibility, Aerobic power, Injury, Soccer, Education, Special aspects of education, LC8-6691, Sports, GV557-1198.995
Abstract

The purpose of this research was to study was the relationship between some of the physical fitness factors and sport injuries in soccer players. 69 senior soccer players (age: 22.83±3.06 yrs.), experienced (9.45±4.56 yrs.), that play in Guilan league participated in this study. Demographic information and sport activity were collected by questionnaire and interviews. Then muscle strength by manual muscle test, flexibility by sit & reach test and aerobic power by Bruce test were assessed. Hawkinz and Fuller questioner with validity of 87% was used for collecting information about risk factors. Correlation coefficient and chi square test were used to analyze data (p≤0.05). The results showed that most injuries were in lower extremity (63.8) and muscular tissue (62.3). Also significant relationship was found between hip flexors strength (p=0.042), trunk flexors strength (p=0.044), trunk extensors strength (p=0.047), flexibility (p=0.022) and aerobic power (p=0.029) with injury. But was no significant relationship between hip extensors strength with injury. There is also significant relationship between experience, dominant leg, non-dominant leg and injury rate (p≤0.05). However was no significant relationship between age with injury rate. With respect to relationship between strength, flexibility and aerobic power (in fact physical fitness) with injury, seems that coaches and players should pay more attention to factors such as strength, aerobic power and flexibility. Also skill and experience of players should be considered carefully.

Published
2018

42. Monitoring Coral Ecosystems in Naiband Bay, the Persian Gulf.

Author

Razaviarabi, Azadeh, Danehkar, Afshin, Monavari, S. Masoud, and Haghshenas, S. Abbas

Subjects
CORALS, GAS fields, OIL fields, SEDIMENTS
Abstract

This paper presents results of some special monitoring plan for the coral system in the Naiband Bay, the Persian Gulf, to assess current conditions of the coral ecosystem in this area which is supposed to be affected by the ongoing developments in the neighboring South Pars Oil Field as well as construction a new port at Haleh in the south east corner of the bay. [ABSTRACT FROM AUTHOR]

Published
2013

44. The role of magnesium supplementation in cisplatin-induced nephrotoxicity in a rat model: No nephroprotectant effect

Author

Ashrafi, F., Haghshenas, S., Nematbakhsh, M., Nasri, H., Ardeshir Talebi, Eshraghi-Jazi, F., Pezeshki, Z., and Safari, T.

Subjects
nephrotoxicity, lcsh:R, lcsh:Medicine, Original Article, rat, Cisplatin, magnesium
Abstract

Objectives: Cisplatin (CP) is used as the commonest drug to treat solid tumors. It is accompanied by a nephrotoxicity side effect. The main objective of this study is to investigate the protective role of magnesium (Mg) supplementation in CP-induced nephrotoxicity in a rat model. Methods: Twenty-nine Wistar rats were randomly assigned to four groups (1-4). Groups 1-3 received 20, 80, and 200 mg/kg magnesium sulfate respectively, for 10 days, but on day 3, a single dose of CP (7 mg/kg, i.p.) was also injected. Group 4 (positive control group) received the same regimen of Groups 1-3 except saline instead magnesium sulfate. One week after CP administration, blood samples were obtained and all animals were killed for kidney histopathological investigations. Results: All CP-treated animals lost weight, and the percentage of weight loss in Group 1 (low dose Mg sulfate treated) was significantly higher compared with the positive control group (Group 4, P < 0.05). The increase in blood urea nitrogen (BUN) and creatinine (Cr) levels in serum in Group 1 were more than those in other groups ( P < 0.05). No statistical differences were observed in serum magnesium, nitrite, and total protein levels among the groups. The kidney tissue damage in Groups 1-3 was not significantly different when compared with Group 4. Moreover, the kidney and testis weights in Group 1 were significantly greater than those in the positive control group (P < 0.05). Conclusion: Regarding the BUN and Cr levels in the serum, kidneys weight, and the histopathological study, the low dose of Mg supplementation intensifies kidney toxicity and renal dysfunction in CP-induced nephrotoxicity in the rat model. However, the protective role of Mg with moderate and high doses is not certain.

48. Clinical Utility of a Unique Genome-Wide DNA Methylation Signature for KMT2A-Related Syndrome

Author

Aidin Foroutan, Sadegheh Haghshenas, Pratibha Bhai, Michael A. Levy, Jennifer Kerkhof, Haley McConkey, Marcello Niceta, Andrea Ciolfi, Lucia Pedace, Evelina Miele, David Genevieve, Solveig Heide, Mariëlle Alders, Giuseppe Zampino, Giuseppe Merla, Mélanie Fradin, Eric Bieth, Dominique Bonneau, Klaus Dieterich, Patricia Fergelot, Elise Schaefer, Laurence Faivre, Antonio Vitobello, Silvia Maitz, Rita Fischetto, Cristina Gervasini, Maria Piccione, Ingrid van de Laar, Marco Tartaglia, Bekim Sadikovic, Anne-Sophie Lebre, Foroutan A., Haghshenas S., Bhai P., Levy M.A., Kerkhof J., McConkey H., Niceta M., Ciolfi A., Pedace L., Miele E., Genevieve D., Heide S., Alders M., Zampino G., Merla G., Fradin M., Bieth E., Bonneau D., Dieterich K., Fergelot P., Schaefer E., Faivre L., Vitobello A., Maitz S., Fischetto R., Gervasini C., Piccione M., van de Laar I., Tartaglia M., Sadikovic B., Lebre A.-S., Human Genetics, ACS - Pulmonary hypertension & thrombosis, ARD - Amsterdam Reproduction and Development, University of Western Ontario (UWO), London Health Sciences Center (LHSC), IRCCS Ospedale Pediatrico Bambino Gesù [Roma], Cellules Souches, Plasticité Cellulaire, Médecine Régénératrice et Immunothérapies (IRMB), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Amsterdam UMC - Amsterdam University Medical Center, University of Amsterdam [Amsterdam] (UvA), Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Università cattolica del Sacro Cuore = Catholic University of the Sacred Heart [Roma] (Unicatt), University of Naples Federico II = Università degli studi di Napoli Federico II, Fondazione Casa Sollievo della Sofferenza [San Giovanni Rotondo, Italy] (FC2S), Service de génétique clinique [Rennes], Université de Rennes (UR)-CHU Pontchaillou [Rennes]-hôpital Sud, Service de génétique [Angers], Université d'Angers (UA)-Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), MitoVasc - Physiopathologie Cardiovasculaire et Mitochondriale (MITOVASC), Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institute for Advanced Biosciences / Institut pour l'Avancée des Biosciences (Grenoble) (IAB), Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang - Auvergne-Rhône-Alpes (EFS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), Laboratoire Maladies Rares: Génétique et Métabolisme (Bordeaux) (U1211 INSERM/MRGM), Université de Bordeaux (UB)-Groupe hospitalier Pellegrin-Institut National de la Santé et de la Recherche Médicale (INSERM), Les Hôpitaux Universitaires de Strasbourg (HUS), Lipides - Nutrition - Cancer [Dijon - U1231] (LNC), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Agro Dijon, Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro), FHU TRANSLAD (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), San Gerardo Hospital [Monza, Italy] (SGH), Hospital Papa Giovanni XXIII (Hosp P Giovanni XXIII), Università degli Studi di Milano = University of Milan (UNIMI), Università degli studi di Palermo - University of Palermo, Erasmus University Medical Center [Rotterdam] (Erasmus MC), Institut de psychiatrie et neurosciences de Paris (IPNP - U1266 Inserm), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Service de génétique [Reims], Centre Hospitalier Universitaire de Reims (CHU Reims), Foroutan, A., Haghshenas, S., Bhai, P., Levy, M. A., Kerkhof, J., Mcconkey, H., Niceta, M., Ciolfi, A., Pedace, L., Miele, E., Genevieve, D., Heide, S., Alders, M., Zampino, G., Merla, G., Fradin, M., Bieth, E., Bonneau, D., Dieterich, K., Fergelot, P., Schaefer, E., Faivre, L., Vitobello, A., Maitz, S., Fischetto, R., Gervasini, C., Piccione, M., van de Laar, I., Tartaglia, M., Sadikovic, B., Lebre, A. -S., Martinez Rico, Clara, and Clinical Genetics

Subjects
Wiedemann–Steiner syndrome, QH301-705.5, Intellectual disability, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Catalysis, Inorganic Chemistry, KMT2A gene, Neurodevelopmental disorder, Growth Disorder, Abnormalities, Multiple, [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Biology (General), Physical and Theoretical Chemistry, Episignature, QD1-999, [SDV.BC] Life Sciences [q-bio]/Cellular Biology, Molecular Biology, Spectroscopy, DNA methylation, Organic Chemistry, Neurodevelopmental disorders, Craniofacial Abnormalitie, Epigenetic, Hypertrichosi, General Medicine, Facie, Computer Science Applications, Chemistry, epigenetics, episignature, intellectual disability, neurodevelopmental disorders, Phenotype, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Epigenetics, Human
Abstract

Wiedemann–Steiner syndrome (WDSTS) is a Mendelian syndromic intellectual disability (ID) condition associated with hypertrichosis cubiti, short stature, and characteristic facies caused by pathogenic variants in the KMT2A gene. Clinical features can be inconclusive in mild and unusual WDSTS presentations with variable ID (mild to severe), facies (typical or not) and other associated malformations (bone, cerebral, renal, cardiac and ophthalmological anomalies). Interpretation and classification of rare KMT2A variants can be challenging. A genome-wide DNA methylation episignature for KMT2A-related syndrome could allow functional classification of variants and provide insights into the pathophysiology of WDSTS. Therefore, we assessed genome-wide DNA methylation profiles in a cohort of 60 patients with clinical diagnosis for WDSTS or Kabuki and identified a unique highly sensitive and specific DNA methylation episignature as a molecular biomarker of WDSTS. WDSTS episignature enabled classification of variants of uncertain significance in the KMT2A gene as well as confirmation of diagnosis in patients with clinical presentation of WDSTS without known genetic variants. The changes in the methylation profile resulting from KMT2A mutations involve global reduction in methylation in various genes, including homeobox gene promoters. These findings provide novel insights into the molecular etiology of WDSTS and explain the broad phenotypic spectrum of the disease.

Published
2022
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49. Functional correlation of genome-wide DNA methylation profiles in genetic neurodevelopmental disorders

Author

Michael A. Levy, Raissa Relator, Haley McConkey, Erinija Pranckeviciene, Jennifer Kerkhof, Mouna Barat‐Houari, Sara Bargiacchi, Elisa Biamino, María Palomares Bralo, Gerarda Cappuccio, Andrea Ciolfi, Angus Clarke, Barbara R. DuPont, Mariet W. Elting, Laurence Faivre, Timothy Fee, Marco Ferilli, Robin S. Fletcher, Florian Cherick, Aidin Foroutan, Michael J. Friez, Cristina Gervasini, Sadegheh Haghshenas, Benjamin A. Hilton, Zandra Jenkins, Simranpreet Kaur, Suzanne Lewis, Raymond J. Louie, Silvia Maitz, Donatella Milani, Angela T. Morgan, Renske Oegema, Elsebet Østergaard, Nathalie R. Pallares, Maria Piccione, Astrid S. Plomp, Cathryn Poulton, Jack Reilly, Rocio Rius, Stephen Robertson, Kathleen Rooney, Justine Rousseau, Gijs W. E. Santen, Fernando Santos‐Simarro, Josephine Schijns, Gabriella M. Squeo, Miya St John, Christel Thauvin‐Robinet, Giovanna Traficante, Pleuntje J. van der Sluijs, Samantha A. Vergano, Niels Vos, Kellie K. Walden, Dimitar Azmanov, Tugce B. Balci, Siddharth Banka, Jozef Gecz, Peter Henneman, Jennifer A. Lee, Marcel M. A. M. Mannens, Tony Roscioli, Victoria Siu, David J. Amor, Gareth Baynam, Eric G. Bend, Kym Boycott, Nicola Brunetti‐Pierri, Philippe M. Campeau, Dominique Campion, John Christodoulou, David Dyment, Natacha Esber, Jill A. Fahrner, Mark D. Fleming, David Genevieve, Delphine Heron, Thomas Husson, Kristin D. Kernohan, Alisdair McNeill, Leonie A. Menke, Giuseppe Merla, Paolo Prontera, Cheryl Rockman‐Greenberg, Charles Schwartz, Steven A. Skinner, Roger E. Stevenson, Marie Vincent, Antonio Vitobello, Marco Tartaglia, Marielle Alders, Matthew L. Tedder, Bekim Sadikovic, Human genetics, Amsterdam Reproduction & Development (AR&D), Pediatrics, Levy M.A., Relator R., McConkey H., Pranckeviciene E., Kerkhof J., Barat-Houari M., Bargiacchi S., Biamino E., Palomares Bralo M., Cappuccio G., Ciolfi A., Clarke A., DuPont B.R., Elting M.W., Faivre L., Fee T., Ferilli M., Fletcher R.S., Cherick F., Foroutan A., Friez M.J., Gervasini C., Haghshenas S., Hilton B.A., Jenkins Z., Kaur S., Lewis S., Louie R.J., Maitz S., Milani D., Morgan A.T., Oegema R., Ostergaard E., Pallares N.R., Piccione M., Plomp A.S., Poulton C., Reilly J., Rius R., Robertson S., Rooney K., Rousseau J., Santen G.W.E., Santos-Simarro F., Schijns J., Squeo G.M., John M.S., Thauvin-Robinet C., Traficante G., van der Sluijs P.J., Vergano S.A., Vos N., Walden K.K., Azmanov D., Balci T.B., Banka S., Gecz J., Henneman P., Lee J.A., Mannens M.M.A.M., Roscioli T., Siu V., Amor D.J., Baynam G., Bend E.G., Boycott K., Brunetti-Pierri N., Campeau P.M., Campion D., Christodoulou J., Dyment D., Esber N., Fahrner J.A., Fleming M.D., Genevieve D., Heron D., Husson T., Kernohan K.D., McNeill A., Menke L.A., Merla G., Prontera P., Rockman-Greenberg C., Schwartz C., Skinner S.A., Stevenson R.E., Vincent M., Vitobello A., Tartaglia M., Alders M., Tedder M.L., Sadikovic B., Levy, Michael A, Relator, Raissa, Mcconkey, Haley, Pranckeviciene, Erinija, Kerkhof, Jennifer, Barat-Houari, Mouna, Bargiacchi, Sara, Biamino, Elisa, Bralo, María Palomare, Cappuccio, Gerarda, Ciolfi, Andrea, Clarke, Angu, Dupont, Barbara R, Elting, Mariet W, Faivre, Laurence, Fee, Timothy, Ferilli, Marco, Fletcher, Robin S, Cherick, Florian, Foroutan, Aidin, Friez, Michael J, Gervasini, Cristina, Haghshenas, Sadegheh, Hilton, Benjamin A, Jenkins, Zandra, Kaur, Simranpreet, Lewis, Suzanne, Louie, Raymond J, Maitz, Silvia, Milani, Donatella, Morgan, Angela T, Oegema, Renske, Østergaard, Elsebet, Pallares, Nathalie Ruiz, Piccione, Maria, Plomp, Astrid S, Poulton, Cathryn, Reilly, Jack, Rius, Rocio, Robertson, Stephen, Rooney, Kathleen, Rousseau, Justine, Santen, Gijs W E, Santos-Simarro, Fernando, Schijns, Josephine, Squeo, Gabriella Maria, John, Miya St, Thauvin-Robinet, Christel, Traficante, Giovanna, van der Sluijs, Pleuntje J, Vergano, Samantha A, Vos, Niel, Walden, Kellie K, Azmanov, Dimitar, Balci, Tugce B, Banka, Siddharth, Gecz, Jozef, Henneman, Peter, Lee, Jennifer A, Mannens, Marcel M A M, Roscioli, Tony, Siu, Victoria, Amor, David J, Baynam, Gareth, Bend, Eric G, Boycott, Kym, Brunetti-Pierri, Nicola, Campeau, Philippe M, Campion, Dominique, Christodoulou, John, Dyment, David, Esber, Natacha, Fahrner, Jill A, Fleming, Mark D, Genevieve, David, Heron, Delphine, Husson, Thoma, Kernohan, Kristin D, Mcneill, Alisdair, Menke, Leonie A, Merla, Giuseppe, Prontera, Paolo, Rockman-Greenberg, Cheryl, Schwartz, Charle, Skinner, Steven A, Stevenson, Roger E, Vincent, Marie, Vitobello, Antonio, Tartaglia, Marco, Alders, Marielle, Tedder, Matthew L, Sadikovic, Bekim, Human Genetics, General Paediatrics, Graduate School, AGEM - Amsterdam Gastroenterology Endocrinology Metabolism, ARD - Amsterdam Reproduction and Development, ANS - Cellular & Molecular Mechanisms, ANS - Complex Trait Genetics, and ACS - Pulmonary hypertension & thrombosis

Subjects
DNA methylation, clinical diagnostics, Syndrome, DNA methylation, clinical diagnostics, episignatures, neurodevelopmental syndromes, neurodevelopmental syndromes, Epigenesis, Genetic, Neurodevelopmental Disorders, Genetics, Humans, CpG Islands, DNA, Intergenic, episignatures, Episignature, Genetics (clinical)
Abstract

An expanding range of genetic syndromes are characterized by genome-wide disruptions in DNA methylation profiles referred to as episignatures. Episignatures are distinct, highly sensitive and specific biomarkers that have recently been applied in clinical diagnosis of genetic syndromes. Episignatures are contained within the broader disorder-specific genome-wide DNA methylation changes which can share significant overlap amongst different conditions. In this study we performed functional genomic assessment and comparison of disorder-specific and overlapping genome-wide DNA methylation changes related to 65 genetic syndromes with previously described episignatures. We demonstrate evidence of disorder-specific and recurring genome-wide differentially methylated probes (DMPs) and regions (DMRs). The overall distribution of DMPs and DMRs across the majority of the neurodevelopmental genetic syndromes analyzed showed substantial enrichment in gene promoters and CpG islands, and under-representation of the more variable intergenic regions. Analysis showed significant enrichment of the DMPs and DMRs in gene pathways and processes related to neurodevelopment, including neurogenesis, synaptic signaling and synaptic transmission. This study expands beyond the diagnostic utility of DNA methylation episignatures by demonstrating correlation between the function of the mutated genes and the consequent genomic DNA methylation profiles as a key functional element in the molecular etiology of genetic neurodevelopmental disorders. This article is protected by copyright. All rights reserved.

Published
2022
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50. Identification of a dna methylation episignature in the 22q11.2 deletion syndrome

Author

Gabriella Maria Squeo, Eleonora Di Venere, Paolo Prontera, Matthew L. Tedder, Sadegheh Haghshenas, Kathleen Rooney, Giuseppe Merla, Daniela Rogaia, Amedea Mencarelli, Jennifer Kerkhof, Michael A. Levy, Bekim Sadikovic, Alberto Verrotti, Maria Giovanna Tedesco, Valentina Imperatore, Giuseppe Di Cara, Barbara R. DuPont, Rooney, K., Levy, M. A., Haghshenas, S., Kerkhof, J., Rogaia, D., Tedesco, M. G., Imperatore, V., Mencarelli, A., Squeo, G. M., Di Venere, E., Di Cara, G., Verrotti, A., Merla, G., Tedder, M. L., Dupont, B. R., Sadikovic, B., and Prontera, P.

Subjects
Male, 22q11.2 deletion, Velocardiofacial syndrome, QH301-705.5, Biology, Article, Catalysis, Inorganic Chemistry, Epigenome, DiGeorge syndrome, Intellectual disability, diagnostic method, medicine, Humans, Biology (General), Physical and Theoretical Chemistry, Episignature, QD1-999, Molecular Biology, Transcription factor, Gene, Spectroscopy, Conotruncalanomaly face syndrome, Genetics, DNA methylation, Organic Chemistry, Infant, General Medicine, Methylation, medicine.disease, Phenotype, Computer Science Applications, Chromatin, episignature, Chemistry, Female, Diagnostic method, Human
Abstract

The 22q11.2 deletion syndrome (22q11.2DS) is the most common genomic disorder in humans and is the result of a recurrent 1.5 to 2.5 Mb deletion, encompassing approximately 20–40 genes, respectively. The clinical presentation of the typical deletion includes: Velocardiofacial, Di George, Opitz G/BBB and Conotruncalanomaly face syndromes. Atypical deletions (proximal, distal or nested) are rare and characterized mainly by normal phenotype or mild intellectual disability and variable clinical features. The pathogenetic mechanisms underlying this disorder are not completely understood. Because the 22q11.2 region harbours genes coding for transcriptional factors and chromatin remodelers, in this study, we performed analysis of genome-wide DNA methylation of peripheral blood from 49 patients with 22q11.2DS using the Illumina Infinium Methylation EPIC bead chip arrays. This cohort comprises 43 typical, 2 proximal and 4 distal deletions. We demonstrated the evidence of a unique and highly specific episignature in all typical and proximal 22q11.2DS. The sensitivity and specificity of this signature was further confirmed by comparing it to over 1500 patients with other neurodevelopmental disorders with known episignatures. Mapping the 22q11.2DS DNA methylation episignature provides both novel insights into the molecular pathogenesis of this disorder and an effective tool in the molecular diagnosis of 22q11.2DS.

Published
2021

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