DEBORA ROMEO BERTOLA
Projetos de Pesquisa
Unidades Organizacionais
Instituto da Criança, Hospital das Clínicas, Faculdade de Medicina - Médico
BIO, IB
LIM/36 - Laboratório de Pediatria Clínica, Hospital das Clínicas, Faculdade de Medicina
BIO, IB
LIM/36 - Laboratório de Pediatria Clínica, Hospital das Clínicas, Faculdade de Medicina
9 resultados
Resultados de Busca
Agora exibindo 1 - 9 de 9
- Serpentine fibula polycystic kidney syndrome is part of the phenotypic spectrum of Hajdu-Cheney syndrome(2012) GRAY, Mary J.; KIM, Chong Ae; BERTOLA, Debora Romeo; ARANTES, Paula Ricci; STEWART, Helen; SIMPSON, Michael A.; IRVING, Melita D.; ROBERTSON, Stephen P.Serpentine fibula polycystic kidney syndrome (SFPKS; MIM600330) is a rare skeletal dysplasia that has polycystic kidneys and dysmorphic facies as additional defining phenotypic components. The nosological classification of this disease has been debated as the condition shares features common to other skeletal dysplasias such as Melnick Needles syndrome (MNS; MIM309350) and Hajdu-Cheney Syndrome (HCS; MIM102500). Here, two previously reported cases of SFPKS are presented with emphasis on their phenotypic evolution. With the recent discovery that HCS is caused by mutations in NOTCH2, DNA from the both cases was examined and both were found to have truncating mutations in exon 34 of NOTCH2. The phenotypic evolution of SFPKS and this molecular analysis strongly suggest that SFPKS is part of the phenotypic spectrum of HCS and should no longer be classified as a distinct disease entity. European Journal of Human Genetics (2012) 20, 122-124; doi:10.1038/ejhg.2011.125; published online 29 June 2011
conferenceObject Severe Osteogenesis imperfecta with oligodontia: think of MESD(2020) MOOSA, S.; YAMAMOTO, G. L.; GARBES, L.; KEUPP, K.; BELEZA-MEIRELES, A.; MORENO, C. A.; VALADARES, E. R.; SOUSA, S. B. de; MAIA, S.; SARAIVA, J.; HONJO, R. S.; KIM, C. A.; MENEZES, H. Cabral de; LAUSCH, E.; LORINI, P. V.; LAMOUNIER JR., A.; CARNIERO, T. C. B.; GIUNTA, C.; ROHRBACH, M.; JANNER, M.; SEMLER, O.; BELEGGIA, F.; LI, Y.; YIGIT, G.; REINTJES, N.; ALTMULLER, J.; NURNBERG, P.; CAVALCANTI, D. P.; ZABEL, B.; WARMAN, M. L.; BERTOLA, D. R.; WOLLNIK, B.; NETZER, C.- Baraitser-Winter cerebrofrontofacial syndrome: delineation of the spectrum in 42 cases(2015) VERLOES, Alain; DONATO, Nataliya Di; MASLIAH-PLANCHON, Julien; JONGMANS, Marjolijn; ABDUL-RAMAN, Omar A.; ALBRECHT, Beate; ALLANSON, Judith; BRUNNER, Han; BERTOLA, Debora; CHASSAING, Nicolas; DAVID, Albert; DEVRIENDT, Koen; EFTEKHARI, Pirayeh; DROUIN-GARRAUD, Valerie; FARAVELLI, Francesca; FAIVRE, Laurence; GIULIANO, Fabienne; ALMEIDA, Leina Guion; JUNCOS, Jorge; KEMPERS, Marlies; EKER, Hatice Kocak; LACOMBE, Didier; LIN, Angela; MANCINI, Grazia; MELIS, Daniela; LOURENCO, Charles Marques; SIU, Victoria Mok; MORIN, Gilles; NEZARATI, Marjan; NOWACZYK, Malgorzata J. M.; RAMER, Jeanette C.; OSIMANI, Sara; PHILIP, Nicole; PIERPONT, Mary Ella; PROCACCIO, Vincent; ROSELI, Zeichi-Seide; ROSSI, Massimiliano; RUSU, Cristina; SZNAJER, Yves; TEMPLIN, Ludivine; ULIANA, Vera; KLAUS, Mirjam; BON, Bregje Van; RAVENSWAAIJ, Conny Van; WAINER, Bruce; FRY, Andrew E.; RUMP, Andreas; HOISCHEN, Alexander; DRUNAT, Severine; RIVIERE, Jean-Baptiste; DOBYNS, William B.; PILZ, Daniela T.Baraitser-Winter, Fryns-Aftimos and cerebrofrontofacial syndrome types 1 and 3 have recently been associated with heterozygous gain-of-function mutations in one of the two ubiquitous cytoplasmic actin-encoding genes ACTB and ACTG1 that encode beta-and gamma-actins. We present detailed phenotypic descriptions and neuroimaging on 36 patients analyzed by our group and six cases from the literature with a molecularly proven actinopathy (9 ACTG1 and 33 ACTB). The major clinical anomalies are striking dysmorphic facial features with hypertelorism, broad nose with large tip and prominent root, congenital non-myopathic ptosis, ridged metopic suture and arched eyebrows. Iris or retinal coloboma is present in many cases, as is sensorineural deafness. Cleft lip and palate, hallux duplex, congenital heart defects and renal tract anomalies are seen in some cases. Microcephaly may develop with time. Nearly all patients with ACTG1 mutations, and around 60% of those with ACTB mutations have some degree of pachygyria with anteroposterior severity gradient, rarely lissencephaly or neuronal heterotopia. Reduction of shoulder girdle muscle bulk and progressive joint stiffness is common. Early muscular involvement, occasionally with congenital arthrogryposis, may be present. Progressive, severe dystonia was seen in one family. Intellectual disability and epilepsy are variable in severity and largely correlate with CNS anomalies. One patient developed acute lymphocytic leukemia, and another a cutaneous lymphoma, indicating that actinopathies may be cancer-predisposing disorders. Considering the multifaceted role of actins in cell physiology, we hypothesize that some clinical manifestations may be partially mutation specific. Baraitser-Winter cerebrofrontofacial syndrome is our suggested designation for this clinical entity.
conferenceObject Sweeney-Cox syndrome: report of the third patient affected by this new delineated syndrome harboring a novel variant in TWIST1(2019) BERTOLA, D.; MUSSO, C. M.; ROCHA, K.; YAMAMOTO, G. L.; PASSOS-BUENO, M.- Genotype and phenotype spectrum of NRAS germline variants(2017) ALTMUELLER, Franziska; LISSEWSKI, Christina; BERTOLA, Debora; FLEX, Elisabetta; STARK, Zornitza; SPRANGER, Stephanie; BAYNAM, Gareth; BUSCARILLI, Michelle; DYACK, Sarah; GILLIS, Jane; YNTEMA, Helger G.; PANTALEONI, Francesca; LOON, Rosa L. E. van; MACKAY, Sara; MINA, Kym; SCHANZE, Ina; TAN, Tiong Yang; WALSH, Maie; WHITE, Susan M.; NIEWISCH, Marena R.; GARCIA-MINAUR, Sixto; PLAZA, Diego; AHMADIAN, Mohammad Reza; CAVE, Helene; TARTAGLIA, Marco; ZENKER, MartinRASopathies comprise a group of disorders clinically characterized by short stature, heart defects, facial dysmorphism, and varying degrees of intellectual disability and cancer predisposition. They are caused by germline variants in genes encoding key components or modulators of the highly conserved RAS-MAPK signalling pathway that lead to dysregulation of cell signal transmission. Germline changes in the genes encoding members of the RAS subfamily of GTPases are rare and associated with variable phenotypes of the RASopathy spectrum, ranging from Costello syndrome (HRAS variants) to Noonan and Cardiofaciocutaneous syndromes (KRAS variants). A small number of RASopathy cases with disease-causing germline NRAS alterations have been reported. Affected individuals exhibited features fitting Noonan syndrome, and the observed germline variants differed from the typical oncogenic NRAS changes occurring as somatic events in tumours. Here we describe 19 new cases with RASopathy due to disease-causing variants in NRAS. Importantly, four of them harbored missense changes affecting Gly12, which was previously described to occur exclusively in cancer. The phenotype in our cohort was variable but well within the RASopathy spectrum. Further, one of the patients (c. 35G > A; p.(Gly12Asp)) had a myeloproliferative disorder, and one subject (c. 34G > C; p.(Gly12Arg)) exhibited an uncharacterized brain tumour. With this report, we expand the genotype and phenotype spectrum of RASopathy-associated germline NRAS variants and provide evidence that NRAS variants do not spare the cancer-associated mutation hotspots.
conferenceObject SCUBE3 loss-of-function causes a recognizable developmental disorder due to defective bone morphogenetic protein (BMP) signaling(2022) NICETA, Marcello; LIN, Yuh-Charn; MUTO, Valentina; VONA, Barbara; PAGNAMENTA, Alistair T.; MAROOFIAN, Reza; BEETZ, Christian; DUYVENVOORDE, Hermine Van; DENTICI, Maria Lisa; LAUFFER, Peter; VALLIAN, Sadeq; CIOLFI, Andrea; PIZZI, Simone; BAUER, Peter; GRUNING, Nana-Maria; BELLACCHIO, Emanuele; FATTORE, Andrea Del; PETRINI, Stefania; SHAHEEN, Ranad; TIOSANO, Dov; HALLOUN, Rana; PODE-SHAKKED, Ben; ALBAYRAK, Hatice Mutlu; ISIK, Emregul; WIT, Jan M.; DITTRICH, Marcus; FREIRE, Bruna L.; BERTOLA, Debora R.; JORGE, Alexander A. L.; BAREL, Ortal; SABIR, Ataf H.; TENEIJI, Amal M. Al; TAJI, Sulaima M.; AL-SANNAA, Nouriya; AL-ABDULWAHED, Hind; DIGILIO, Maria Cristina; IRVING, Melita; ANIKSTER, Yair; BHAVANI, Gandham S. L.; GIRISHA, Katta M.; HAAF, Thomas; TAYLOR, Jenny C.; DALLAPICCOLA, Bruno; ALKURAYA, Fowzan S.; YANG, Ruey-Bing; TARTAGLIA, MarcoconferenceObject Phenotype Assessment of a Brazilian Cornelia de Lange Syndrome (CDLS) cohort(2019) KIM, V. E. H.; FURQUIM, I.; CERONI, J. R. M.; CASTRO, P. H. S.; OLIVATI, C.; BERLIM, C.; LOPES, D. M. B.; PIMENTA, L.; HONJO, R. S.; BERTOLA, D. R.; KIM, C. A.conferenceObject Overlapping phenotypes in patients harboring heterozygous mutations in KAT6A and KAT6B(2019) ESTRELLA, S.; BERTOLA, D.; YAMAMOTO, G. L.; HONJO, R.; CERONI, J. R.; KIM, C. A.- Patients with a Kabuki syndrome phenotype demonstrate DNA methylation abnormalities(2017) SOBREIRA, Nara; BRUCATO, Martha; ZHANG, Li; LADD-ACOSTA, Christine; ONGACO, Chrissie; ROMM, Jane; DOHENY, Kimberly F.; MINGRONI-NETTO, Regina C.; BERTOLA, Debora; KIM, Chong A.; PEREZ, Ana B. A.; MELARAGNO, Maria I.; VALLE, David; MELONI, Vera A.; BJORNSSON, Hans T.Kabuki syndrome is a monogenic disorder caused by loss of function variants in either of two genes encoding histone-modifying enzymes. We performed targeted sequencing in a cohort of 27 probands with a clinical diagnosis of Kabuki syndrome. Of these, 12 had causative variants in the two known Kabuki syndrome genes. In 2, we identified presumptive loss of function de novo variants in KMT2A (missense and splice site variants), a gene that encodes another histone modifying enzyme previously exclusively associated with Wiedermann-Steiner syndrome. Although Kabuki syndrome is a disorder of histone modification, we also find alterations in DNA methylation among individuals with a Kabuki syndrome diagnosis relative to matched normal controls, regardless of whether they carry a variant in KMT2A or KMT2D or not. Furthermore, we observed characteristic global abnormalities of DNA methylation that distinguished patients with a loss of function variant in KMT2D or missense or splice site variants in either KMT2D or KMT2A from normal controls. Our results provide new insights into the relationship of genotype to epigenotype and phenotype and indicate cross-talk between histone and DNA methylation machineries exposed by inborn errors of the epigenetic apparatus.