CHONG AE KIM
Projetos de Pesquisa
Unidades Organizacionais
Departamento de Pediatria, Faculdade de Medicina - Docente
LIM/36 - Laboratório de Pediatria Clínica, Hospital das Clínicas, Faculdade de Medicina - Líder
LIM/03 - Laboratório de Medicina Laboratorial, Hospital das Clínicas, Faculdade de Medicina
LIM/36 - Laboratório de Pediatria Clínica, Hospital das Clínicas, Faculdade de Medicina - Líder
LIM/03 - Laboratório de Medicina Laboratorial, Hospital das Clínicas, Faculdade de Medicina
15 resultados
Resultados de Busca
Agora exibindo 1 - 10 de 15
- Mucopolysaccharidosis type VI: case report with first neonatal presentation with ascites fetalis and rapidly progressive cardiac manifestation(2020) HONJO, Rachel Sayuri; VACA, Evelyn Cristina Nunez; LEAL, Gabriela Nunes; ABELLAN, Deipara Monteiro; IKARI, Nana Miura; JATENE, Marcelo Biscegli; MARTINS, Ana Maria; KIM, Chong AeBackground The Mucopolysaccharidosis type VI (MPS VI), also known as Maroteaux-Lamy syndrome (OMIM 253200) is an autosomal recessive lysosomal disorder, caused by the deficiency of the enzyme N-acetylgalactosamine 4-sulfatase (also known as arylsulfatase B) due to mutations of the ARSB gene. Cardiologic features are well recognized, and are always present in MPS VI patients. Generally, the onset and the progression of the cardiologic symptoms are insidious, and just a few patients have developed a rapidly progressive disease. Cardiac involvement in MPS VI is a common and progressive feature. For MPS patients, cardiac evaluations are recommended every 1 to 2 years, including blood pressure measurement, electrocardiography and echocardiography. However, congestive heart failure and valvular surgical repair are not frequently seen, and if so, they are performed in adults. Here we report on an atypical MPS VI case with ascites fetalis and a rapidly progressive cardiac disease. Case presentation A 6-month-old Brazilian male, only child of a Brazilian healthy non-consanguineous couple. During pregnancy, second trimester ultrasonography observed fetal ascites and bilateral hydrocele. Physical exam at 6 months-old revealed a typical gibbus deformity and MPS was suspected. Biochemical investigation revealed a diagnosis of MPS type VI, confirmed by molecular test. Baseline echocardiogram revealed discrete tricuspid regurgitation and a thickened mitral valve with posterior leaflet prolapse, causing moderate to severe regurgitation. The patient evolved with mitral insufficiency and congestive heart failure, eventually requiring surgical repair by the first year of age. Conclusions We report the first case of MPS VI whose manifestations started in the prenatal period with fetal ascites, with severe cardiac valvular disease that eventually required early surgical repair. Moreover, in MPS with neonatal presentation, including fetal hydrops, besides MPS I, IVA and VII, clinicians should include MPS VI in the differential diagnosis.
bookPart Anomalias congênitas(2020) KIM, Chong Ae; KULIKOWSKI, Leslie Domenici- Loss of TNR causes a nonprogressive neurodevelopmental disorder with spasticity and transient opisthotonus(2020) WAGNER, Matias; LEVY, Jonathan; JUNG-KLAWITTER, Sabine; BAKHTIARI, Somayeh; MONTEIRO, Fabiola; MAROOFIAN, Reza; BIERHALS, Tatjana; HEMPEL, Maja; ELMALEH-BERGES, Monique; KITAJIMA, Joao P.; KIM, Chong A.; SALOMAO, Julia G.; AMOR, David J.; COOPER, Monica S.; PERRIN, Laurence; PIPIRAS, Eva; NEU, Axel; DOOSTI, Mohammad; KARIMIANI, Ehsan G.; TOOSI, Mehran B.; HOULDEN, Henry; JIN, Sheng Chih; SI, Yue C.; RODAN, Lance H.; VENSELAAR, Hanka; KRUER, Michael C.; KOK, Fernando; HOFFMANN, Georg F.; STROM, Tim M.; WORTMANN, Saskia B.; TABET, Anne-Claude; OPLADEN, ThomasPurpose TNR, encoding Tenascin-R, is an extracellular matrix glycoprotein involved in neurite outgrowth and neural cell adhesion, proliferation and migration, axonal guidance, myelination, and synaptic plasticity. Tenascin-R is exclusively expressed in the central nervous system with highest expression after birth. The protein is crucial in the formation of perineuronal nets that ensheath interneurons. However, the role of Tenascin-R in human pathology is largely unknown. We aimed to establish TNR as a human disease gene and unravel the associated clinical spectrum. Methods Exome sequencing and an online matchmaking tool were used to identify patients with biallelic variants in TNR. Results We identified 13 individuals from 8 unrelated families with biallelic variants in TNR sharing a phenotype consisting of spastic para- or tetraparesis, axial muscular hypotonia, developmental delay, and transient opisthotonus. Four homozygous loss-of-function and four different missense variants were identified. Conclusion We establish TNR as a disease gene for an autosomal recessive nonprogressive neurodevelopmental disorder with spasticity and transient opisthotonus and highlight the role of central nervous system extracellular matrix proteins in the pathogenicity of spastic disorders.
- Gene expression profile suggesting immunological dysregulation in two Brazilian Bloom's syndrome cases(2020) MONTENEGRO, Marilia M.; QUAIO, Caio R.; PALMEIRA, Patricia; GASPARINI, Yanca; RANGEL-SANTOS, Andreia; DAMASCENO, Julian; NOVAK, Estela M.; GIMENEZ, Thamires M.; YAMAMOTO, Guilherme L.; RONJO, Rachel S.; NOVO-FILHO, Gil M.; CHEHIMI, Samar N.; ZANARDO, Evelin A.; DIAS, Alexandre T.; NASCIMENTO, Amom M.; COSTA, Thais V. M. M.; DUARTE, Alberto J. da S.; COUTINHO, Luiz L.; KIM, Chong A.; KULIKOWSKI, Leslie D.Background Bloom syndrome (BS) is a rare autosomal recessive chromosome instability disorder. The main clinical manifestations are growth deficiency, telangiectasic facial erythema, immunodeficiency, and increased risk to develop neoplasias at early age. Cytogenetic test for sister chromatid exchanges (SCEs) is used as a diagnostic marker for BS. In addition, most patients also present mutations in the & x202f;BLM & x202f;gene, related to defects in the DNA repair mechanism. However, the molecular mechanism behind the pathogenicity of BS is & x202f;still & x202f;not completely understood. Methods We describe two patients confirmed with BS by SCE and molecular analysis. Also, we performed the gene expression profile by the RNA-seq methodology in mRNA transcripts for differential gene expression analysis using as a biological condition for comparison BS versus health controls. Results We detected 216 differentially expressed genes related to immunological pathways such as positive regulation and activation of B cells, immune effector process and absence of difference of DNA repair genes expression. In addition; we also observed differentially expressed genes associated with apoptosis control, such as BCL2L1, CASP7, CDKN1A, E2F2, ITPR, CD274, TNFAIP6, TNFRSF25, TNFRSF13C, and TNFRSF17. Conclusion Our results suggest that the combination of altered expression of genes involved in signaling pathways of immune response and apoptosis control may contribute directly to the main characteristics observed in BS, such as recurrent infections, growth failure, and high risk of cancer. Transcriptome studies of other instability syndromes could allow a more accurate analysis of the relevant gene interactions associated with the destabilization of the genome. This is a first description of the profile of differential gene expression related to immunological aspects detected in patients with BS by RNA-seq.
- Growth and Clinical Characteristics of Children with Floating-Harbor Syndrome: Analysis of Current Original Data and a Review of the Literature(2020) HOMMA, Thais K.; FREIRE, Bruna L.; HONJO, Rachel; DAUBER, Andrew; FUNARI, Mariana F. A.; LERARIO, Antonio M.; ALBUQUERQUE, Edoarda V. A.; VASQUES, Gabriela A.; BERTOLA, Debora R.; KIM, Chong A.; MALAQUIAS, Alexsandra C.; JORGE, Alexander A. L.Background: Floating-Harbor syndrome (FHS) is a rare condition characterized by dysmorphic facial features, short stature, and expressive language delay. Objective: The aim of this study was to describe a cohort of patients with FHS and review the literature about the response to recombinant human growth hormone (rhGH) therapy. Methods: Anthropometric and laboratory data from 7 patients with FHS were described. The molecular diagnosis was established by multigene analysis. Moreover, we reviewed the literature concerning patients with FHS treated with rhGH. Results: All 7 patients were born small for gestational age. At first evaluation, 6 patients had a height standard deviation score (SDS) <=-2 and 1 had short stature in relation to their target height. Bone age was usually delayed, which rapidly advanced during puberty. Nonspecific skeletal abnormalities were frequently noticed, and normal to elevated plasma IGF-I levels were observed in all except 1 patient with growth hormone deficiency. Information about 20 patients with FHS treated with rhGH was analyzed (4 from our cohort and 16 from the literature). The median height changes during the treatment period (approx. 2.9 years) were 1.1 SDS (range from -0.4 to 3.1). Nontreated patients had an adult height SDS of -4.1 +/- 1.2 (n = 10) versus -2.6 +/- 0.8 SDS (n = 7, p 0.012) for treated patients. Conclusion: We observed a laboratory profile compatible with IGF-1 insensitivity in some patients with FHS. Nevertheless, our study suggests that children with FHS may be considered as candidates for rhGH therapy. Further studies are necessary to establish the real benefit and safety of rhGH therapy in these patients.
- Lymphoproliferative disorder with polyautoimmunity and hypogammaglobulinemia: An unusual presentation of 22q11.2 deletion syndrome(2020) SOARES, Diogo C.; DANTAS, Anelisa G.; MATTA, Marina C.; PASTORINO, Antonio C.; MELARAGNO, Maria Isabel; KULIKOWSKI, Leslie; MONTENEGRO, Marilia; KIM, Chong A.; CARNEIRO-SAMPAIO, Magda; TORRES, Leuridan C.22q11.2 deletion syndrome (22q11.2DS) has a heterogeneous presentation that includes multiple congenital anomalies and immunodeficiency, one of the most striking features. Usually, it is characterized by T cell lymphopenia, B cell dysfunction and autoimmunity. Here, we describe an unusual case of 22q11.2DS in a patient with lymphoproliferative disorder, polyautoimmunity and hypogammaglobulinemia.
- Phenotype-genotype analysis of 242 individuals with RASopathies: 18-year experience of a tertiary center in Brazil(2020) BERTOLA, Debora R.; CASTRO, Matheus A. A.; YAMAMOTO, Guilherme L.; HONJO, Rachel S.; CERONI, Jose Ricardo; BUSCARILLI, Michele M.; FREITAS, Amanda B.; MALAQUIAS, Alexsandra C.; PEREIRA, Alexandre C.; JORGE, Alexander A. L.; PASSOS-BUENO, Maria Rita; KIM, Chong A.We report the clinical and molecular data of a large cohort comprising 242 individuals with RASopathies, from a single Tertiary Center in Brazil, the largest study from Latin America. Noonan syndrome represented 76% of the subjects, with heterozygous variants in nine different genes, mainly PTPN11, SOS1, RAF1, LZTR1, and RIT1, detected by Sanger and next-generation sequencing. The latter was applied to 126 individuals, with a positive yield of 63% in genes of the RAS/MAPK cascade. We present evidence that there are some allelic differences in PTPN11 across distinct populations. We highlight the clinical aspects that pose more medical concerns, such as the cardiac anomalies, bleeding diathesis and proliferative lesions. The genotype-phenotype analysis between the RASopathies showed statistically significant differences in some cardinal features, such as craniofacial and cardiac anomalies, the latter also statistically significant for different genes in Noonan syndrome. We present two individuals with a Noonan syndrome phenotype, one with an atypical, structural cardiac defect, harboring variants in genes mainly associated with isolated hypertrophic cardiomyopathy and discuss the role of these variants in their phenotype.
- Genetic investigation of patients with tall stature(2020) ALBUQUERQUE, Edoarda Vasco de Albuquerque; FUNARI, Mariana Ferreira de Assis; QUEDAS, Elisangela Pereira de Souza; KAWAHIRA, Rachel Sayuri Honjo; JALLAD, Raquel Soares; HOMMA, Thais Kataoka; MARTIN, Regina Matsunaga; BRITO, Vinicius Nahime; MALAQUIAS, Alexsandra Christianne; LERARIO, Antonio Marcondes; ROSENBERG, Carla; KREPISCHI, Ana Cristina Victorino; KIM, Chong Ae; ARNHOLD, Ivo Jorge Prado; JORGE, Alexander Augusto de LimaContext: Patients with tall stature often remain undiagnosed after clinical investigation and few studies have genetically assessed this group, most of them without a systematic approach. Objective: To assess prospectively a group of individuals with tall stature, with and without syndromic features, and to establish a molecular diagnosis for their growth disorder. Design: Screening by karyotype (n = 42), chromosome microarray analyses (CMA) (n = 16), MS-MLPA (n = 2) targeted panel (n = 12) and whole-exome sequencing (n = 31). Patients and methods: We selected 42 patients with tall stature after exclusion of pathologies in GH/IGF1 axis and divided them into syndromic (n = 30) and non-syndromic (n = 12) subgroups. Main outcome measures: Frequencies of pathogenic findings. Results: We identified two patients with chromosomal abnormalities including SHOX trisomy by karyotype, one 9q22.3 microdeletion syndrome by CMA, two cases of Beckwith-Wiedemann syndrome by targeted MS-MLPA analysis and nine cases with heterozygous pathogenic or likely pathogenic genetic variants by multigene analysis techniques (FBN1 = 3, NSD1 = 2, NFIX = 1, SUZ12 = 1, CHD8 = 1, MC4R = 1). Three of 20 patients analyzed by WES had their diagnosis established. Only one non-syndromic patient had a definitive diagnosis. The sequential genetic assessment diagnosed 14 out of 42 (33.3%) tall patients. Conclusion: A systematic molecular approach of patients with tall stature was able to identify the etiology in 13 out of 30 (43.3%) syndromic and 1 out of 12 (8.3%) non-syndromic patients, contributing to the genetic counseling and avoiding unfavorable outcomes in the syndromic subgroup.
conferenceObject Investigation of indel variants in candidate-gene panel for 22q11.2 deletion syndrome(2020) NUNES, N.; DANTAS, A. G.; ZAMARIOLLI, M.; SOARES, D. C. Q.; SANTOS, L. C. dos; MELONI, V. A.; BELANGERO, S. I.; GIL-DA-SILVA-LOPES, V. L.; KIM, C. A.; MELARAGNO, M. I.- Targeted massively parallel sequencing for congenital generalized lipodystrophy(2020) COSTA-RIQUETTO, Aline D.; SANTANA, Lucas S.; CAETANO, Lilian A.; LERARIO, Antonio M.; CORREIA-DEUR, Joya E. M.; BERTOLA, Debora R.; KIM, Chong A.; NERY, Marcia; JORGE, Alexander A. L.; TELES, Milena G.Objective. Our aim is to establish genetic diagnosis of congenital generalized lipodystrophy (CGL) using targeted massively parallel sequencing (MPS), also known as next-generation sequencing (NGS). Subjects and methods: Nine unrelated individuals with a clinical diagnosis of CGL were recruited. We used a customized panel to capture genes related to genetic lipodystrophies. DNA libraries were generated, sequenced using the Illumina MiSeq, and bioinformatics analysis was performed. Results: An accurate genetic diagnosis was stated for all nine patients. Four had pathogenic variants in AGPAT2 and three in BSCL2. Three large homozygous deletions in AGPAT2 were identified by copy-number variant analysis. Conclusions: Although we have found allelic variants in only 2 genes related to CGL, the panel was able to identify different variants including deletions that would have been missed by Sanger sequencing. We believe that MPS is a valuable tool for the genetic diagnosis of multi-genes related diseases, including CGL.