FLAVIA BALBO PIAZZON
Projetos de Pesquisa
Unidades Organizacionais
LIM/03 - Laboratório de Medicina Laboratorial, Hospital das Clínicas, Faculdade de Medicina
7 resultados
Resultados de Busca
Agora exibindo 1 - 7 de 7
- Subacute Partially Reversible Leukoencephalopathy Expands the Aicardi-Goutieres Syndrome Phenotype(2023) BARCELOS, Isabella Peixoto de; BUENO, Clarissa; GODOY, Luis Filipe S.; PESSOA, Andre; COSTA, Larissa A.; MONTI, Fernanda C.; SOUZA-CABRAL, Katiane; LISTIK, Clarice; CASTRO, Diego; DELLA-RIPA, Bruno; FREUA, Fernando; PIRES, Lais C.; KRUGER, Lia T.; GHERPELLI, Jose Luiz D.; PIAZZON, Flavia B.; MONTEIRO, Fabiola P.; LUCATO, Leandro T.; KOK, FernandoObjective: To report a series of atypical presentations of Aicardi-Goutieres syndrome. Methods: Clinical, neuroimaging, and genetic data. Results: We report a series of six unrelated patients (five males) with a subacute loss of developmental milestones, pyramidal signs, and regression of communication abilities, with onset at ages ranging from 7 to 20 months, reaching a nadir after 4 to 24 weeks. A remarkable improvement of lost abilities occurred in the follow-up, and they remained with residual spasticity and dysarthria but preserved cognitive function. Immunization or febrile illness occurred before disease onset in all patients. CSF was normal in two patients, and in four, borderline or mild lymphocytosis was present. A brain CT scan disclosed a subtle basal ganglia calcification in one of six patients. Brain MRI showed asymmetric signal abnormalities of white matter with centrum semi-ovale involvement in five patients and a diffuse white matter abnormality with contrast enhancement in one. Four patients were diagnosed and treated for acute demyelinating encephalomyelitis (ADEM). Brain imaging was markedly improved with one year or more of follow-up (average of 7 years), but patients remained with residual spasticity and dysarthria without cognitive impairment. Demyelination relapse occurred in a single patient four years after the first event. Whole-exome sequencing (WES) was performed in all patients: four of them disclosed biallelic pathogenic variants in RNASEH2B (three homozygous p.Ala177Thr and one compound heterozygous p.Ala177Thr/p.Gln58*) and in two of them the same homozygous deleterious variants in RNASEH2A (p.Ala249Val). Conclusions: This report expands the phenotype of AGS to include subacute developmental regression with partial clinical and neuroimaging improvement. Those clinical features might be misdiagnosed as ADEM.
- Complex small supernumerary marker chromosome with a 15q/16p duplication: clinical implications(2014) CHRISTOFOLINI, Denise M.; PIAZZON, Flavia B.; EVO, Carolina; MAFRA, Fernanda A.; COSENZA, Stella R.; DIAS, Alexandre T.; BARBOSA, Caio P.; BIANCO, Bianca; KULIKOWSKI, Leslie D.Background: Complex small supernumerary marker chromosomes (sSMCs) consist of chromosomal material derived from more than one chromosome and have been implicated in reproductive problems such as recurrent pregnancy loss. They may also be associated with congenital abnormalities in the offspring of carriers. Due to its genomic architecture, chromosome 15 is frequently associated with rearrangements and the formation of sSMCs. Recently, several different CNVs have been described at 16p11.2, suggesting that this region is prone to rearrangements. Results: We detected the concomitant occurrence of partial trisomy 15q and 16p, due to a complex sSMC, in a 6-year-old girl with clinical phenotypic. The karyotype was analyzed by G and C banding, NOR staining, FISH and SNP array and defined as 47,XX,+der(15)t(15;16)(q13;p13.2)mat. The array assay revealed an unexpected complex sSMC containing material from chromosomes 15 and 16, due to an inherited maternal translocation (passed along over several generations). The patient's phenotype included microsomia, intellectual disability, speech delay, hearing impairment, dysphagia and other minor alterations. Discussion: This is the first report on the concomitant occurrence of partial trisomy 15q and 16p. The wide range of phenotypes associated with complex sSMCs represents a challenge for genotype-phenotype correlation studies, accurate clinical assessment of patients and genetic counseling.
- Influenceofbloodphenylalaninelevelvariationsonthedevelopmentofexecutivefunctionsandsocialcognitioninchildrenwithphenylketonuria(2023) DUARTE, Cristiane Mendes de Almeida; PIAZZON, Flavia Balbo; ROCCO, Isadora Salvador; MELLO, Claudia Berlim deToinvestigatetheperformanceof27childrenwithphenylketonuria(PKU) intestsofExecutiveFunctions( EF) andSocialCognition(SC), andtheirassociationswithmetaboliccontrolinferredbyphenylalanine( Phe) levels. Methods: ThePKUgroupwasdichotomizedaccordingtobaselinePhe-levelsinto;""classicalPKU""( n= 14), withPhe-levelsabove1200mmol/L(> 20mg/dL); and""mildPKU""(n= 13) withPhebetween360and1200mmol/L(6-20mg/dL). TheneuropsychologicalassessmentfocusedontheEFandSCsubtestsoftheNEPSYIIbatteryandintellectualperformance. Childrenwerecomparedtoagematchedhealthyparticipants. Results: ParticipantswithPKUpresentedsignificantlylowerIntellectualQuotient(IQ) comparedtocontrols( p= 0.001). RegardingEFanalysisadjustedbyageandIQ, significantdifferencesbetweengroupswereobservedonlyintheexecutiveattentionsubtests( p= 0.029). TheSCsetofvariableswassignificantlydifferentbetweengroups( p= 0.003), asintheaffectiverecognitiontask(p< 0.001). InthePKUgroup, therelativevariationofPhe-achieved32.1 +/- 21.0%. RelativePhe-variationwascorrelatedonlywithmeasuresofWorkingMemory(p< 0.001), VerbalFluency( p= 0.004), InhibitoryControl(p= 0.035) andTheoryofMind(p= 0.003). Conclusions: PhonologicalVerbalFluency, WorkingMemory, InhibitoryControl, andTheoryofMindwereshowntobemostvulnerablewhenthereisnonidealmetaboliccontrol. VariationsinthelevelofPhemayhaveaselectivenegativeeffectonExecutiveFunctionsandSocialCogni- tion, butnotonintellectualperformance.
- Biochemical profile in an infant with neonatal hemochromatosis shows evidence of impairment of mitochondrial long-chain fatty acid oxidation(2019) BASTOS, Karina Lucio de Medeiros; QUAIO, Caio Robledo; LIMA, Fabiana Roberto; ARAUJO, Iana Manuelle; ARAUJO, Candice Alves Tavares; PIAZZON, Flavia Balbo; SILVA, Ismael Dale Cotrim Guerreiro da; BENEVIDES, Gabriel Nuncio; TANNURI, Ana Cristina; TANNURI, Uenis; AZEVEDO, Ramiro Anthero; KIM, Chong Ae
- Cytogenomic assessment of the diagnosis of 93 patients with developmental delay and multiple congenital abnormalities: The Brazilian experience(2017) ZANARDO, Evelin Aline; DUTRA, Roberta Lelis; PIAZZON, Flavia Balbo; DIAS, Alexandre Torchio; NOVO-FILHO, Gil Monteiro; NASCIMENTO, Amom Mendes; MONTENEGRO, Marilia Moreira; DAMASCENO, Jullian Gabriel; MADIA, Fabricia Andreia Rosa; COSTA, Thais Virginia Moura Machado da; MELARAGNO, Maria Isabel; KIM, Chong Ae; KULIKOWSKI, Leslie DomeniciOBJECTIVE: The human genome contains several types of variations, such as copy number variations, that can generate specific clinical abnormalities. Different techniques are used to detect these changes, and obtaining an unequivocal diagnosis is important to understand the physiopathology of the diseases. The objective of this study was to assess the diagnostic capacity of multiplex ligation-dependent probe amplification and array techniques for etiologic diagnosis of syndromic patients. METHODS: We analyzed 93 patients with developmental delay and multiple congenital abnormalities using multiplex ligation-dependent probe amplifications and arrays. RESULTS: Multiplex ligation-dependent probe amplification using different kits revealed several changes in approximately 33.3% of patients. The use of arrays with different platforms showed an approximately 53.75% detection rate for at least one pathogenic change and a 46.25% detection rate for patients with benign changes. A concomitant assessment of the two techniques showed an approximately 97.8% rate of concordance, although the results were not the same in all cases. In contrast with the array results, the MLPA technique detected B70.6% of pathogenic changes. CONCLUSION: The obtained results corroborated data reported in the literature, but the overall detection rate was higher than the rates previously reported, due in part to the criteria used to select patients. Although arrays are the most efficient tool for diagnosis, they are not always suitable as a first-line diagnostic approach because of their high cost for large-scale use in developing countries. Thus, clinical and laboratory interactions with skilled technicians are required to target patients for the most effective and beneficial molecular diagnosis.
- A Multicentric Brazilian Investigative Study of Copy Number Variations in Patients with Congenital Anomalies and Intellectual Disability(2018) CERONI, J. R. M.; DUTRA, R. L.; HONJO, R. S.; LLERENA JR., J. C.; ACOSTA, A. X.; MEDEIROS, P. F. V.; GALERA, M. F.; ZANARDO, E. A.; PIAZZON, F. B.; DIAS, A. T.; NOVO-FILHO, G. M.; MONTENEGRO, M. M.; MADIA, F. A. R.; BERTOLA, D. R.; MELO, J. B. de; KULIKOWSKI, L. D.; KIM, C. A.Genomic imbalances are the most common cause of congenital anomalies (CA) and intellectual disability (ID). The aims of this study were to identify copy number variations (CNVs) in 416 patients with CA and ID from 5 different genetics centers within 4 different states by using the Multiplex Ligation-dependent Probe Amplification (MLPA) technique and to apply the chromosomal microarray (CMA) methodology in selected cases. The samples were analyzed by MLPA kits P064, P036, P070 and P250. Positive results were found in 97/416 (23.3%) patients. CMA was applied in 14 selected cases. In 6/14 (42.85%) patients, CMA detected other copy number variations not detected by the MLPA studies. Although CMA is indispensable for genotype refinement, the technique is still unfeasible in some countries as a routine analysis due to economic and technical limitations. In these cases, clinical evaluation followed by karyotyping and MLPA analysis is a helpful and affordable solution for diagnostic purposes.
- Allan-Herndon-Dudley syndrome in a female patient and related mechanisms(2022) OLIVATI, Caroline; FAVILLA, Bianca Pereira; FREITAS, Erika Lopes; SANTOS, Bibiana; MELARAGNO, Maria Isabel; MELONI, Vera Ayres; PIAZZON, FlaviaAllan-Herndon-Dudley syndrome (AHDS) is characterized by neuropsychomotor developmental delay/intellectual disability, neurological impairment with a movement disorder, and an abnormal thyroid hormone profile. This disease is an X-linked disorder that mainly affects men. We described a female patient with a de novo variant in the SLC16A2 gene, a milder AHDS phenotype, and a skewed X chromosome inactivation profile. We discuss the mechanisms associated with the expression of the phenotypic characteristics in female patients, including SLC16A2 gene variants and cytogenomic alterations, as well as preferential inactivation of the normal X chromosome.