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
12 resultados
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- Lower urinary tract symptoms in children and adolescents with Williams-Beuren syndrome(2017) SAMMOUR, Z. M.; BESSA JR., J. de; HISANO, M.; BRUSCHINI, H.; KIM, C. A.; SROUGI, M.; GOMES, C. M.Introduction Williams-Beuren syndrome (WBS) is a genetic condition caused by a microscopic deletion in the chromosome band 7q11.23. Individuals with WBS may present with congenital cardiovascular defects, neurodevelopmental disturbances and structural abnormalities of the urinary tract. Lower urinary tract symptoms (LUTS) seem to be frequent in this population, but studies on this topic are scarce and based on small case series. Objective To systematically evaluate the prevalence of lower urinary tract symptoms (LUTS) and the acquisition of bladder control in a large population with WBS. Study design A cross-sectional study evaluating 87 consecutive patients with WBS; there were 41 girls and 46 boys. Genetic studies confirmed WBS in all patients. Subjects were clinically evaluated with: a history of LUTS obtained from the parents and child, a structured questionnaire of LUTS, a 3-day urinary frequency-volume chart, a quality of life question regarding LUTS, and physical examination. A history regarding the acquisition of bladder control was directly evaluated from the parents. Results Mean age of patients was 9.0 +/- 4.2 years, ranging from 3 to 19 years. Based on the symptoms questionnaire and the frequency-volume chart, 70 patients (80.5%) were symptomatic. The most common symptom was urgency, affecting 61 (70.1%) patients, followed by increased urinary frequency in 60 (68.9%) patients, and urge-incontinence in 53 (60.9%), as shown in Summary Fig. More than half of the children reported nocturnal enuresis, including 61% of the girls and 52% of the boys. Twenty-three patients (25.6%) had a history of urinary tract infections. The mean age for acquisition of dryness during the day was 4.4 +/- 1.9 years. Parents of 61 patients (70.1%) acknowledged that LUTS had a significant impact on the quality of life of their children. Discussion A high prevalence of LUTS was confirmed with a significant negative impact on quality of life in a large population of children and adolescents with WBS. It was shown for the first time that the achievement of daytime bladder control is delayed in children with WBS. Although LUTS are not recognized as one of the leading features of the syndrome, it is believed that it should be considered as a significant characteristic of the clinical diagnosis of WBS. Conclusions LUTS are highly prevalent in children and adolescents with WBS and have a significant negative impact on patient's quality of life.
bookPart Displasias esqueléticas(2017) KIM, Chong Ae; BERTOLA, Débora Romeo; ALBANO, Lilian Maria José- Herpetiform keratitis and palmoplantar hyperkeratosis: warning signs for Richner-Hanhart syndrome(2017) SOARES, Diogo C.; STROPARO, Mariana N.; LIAN, Yu C.; TAKAKURA, Cristina Y.; WOLF, Sabrina; BETZ, Regina; KIM, Chong A.Richner-Hanhart syndrome (RHS, tyrosinemia type II) is a rare, autosomal recessive inborn error of tyrosine metabolism caused by tyrosine aminotransferase deficiency. It is characterized by photophobia due to keratitis, painful palmoplantar hyperkeratosis, variable mental retardation, and elevated serum tyrosine levels. Patients are often misdiagnosed with herpes simplex keratitis. We report on a a boy from Brazil who presented with bilateral keratitis secondary to RHS, which had earlier been misdiagnosed as herpes simplex keratitis.
conferenceObject 16q24 DUPLICATION AND IVEMARK SYNDROME: A NOVEL GENOMIC CAUSE?(2017) SOARES, Diogo C.; PIAZZON, Flavia B.; ZANARDO, Evelin; PASTORINO, Antonio Carlos; KULIKOWSKI, Leslie D.; BERTOLA, Debora R.; CARNEIRO-SAMPAIO, Magda; KIM, Chong Ae- GNPTAB missense mutations cause loss of GlcNAc-1-phosphotransferase activity in mucolipidosis type II through distinct mechanisms(2017) LUDWIG, Nataniel Floriano; VELHO, Renata Voltolini; SPERB-LUDWIG, Fernanda; ACOSTA, Angelina Xavier; RIBEIRO, Erlane Marques; KIM, Chong A.; HOROVITZ, Dafne Dam Gandelman; BOY, Raquel; RODOVALHO-DORIQUI, Maria Juliana; LOURENCO, Charles Marques; SANTOS, Emerson Santana; BRAULKE, Thomas; POHL, Sandra; SCHWARTZ, Ida Vanessa D.Mucolipidoses (ML) II and III alpha/beta are lysosomal storage diseases caused by pathogenic mutations in GNPTAB encoding the alpha/beta-subunit precursor of GlcNAc-1-phosphotransferase. To determine genotype-phenotype correlation and functional analysis of mutant GlcNAc-1-phosphotransferase, 13 Brazilian patients clinically and biochemical diagnosed for MLII or III alpha/beta were studied. By sequencing of genomic GNPTAB of the MLII and MLIII alpha/beta patients we identified six novel mutations: p.D76G, p.S385L, p.Q278Kfs*3, p.H588Qfs*27, p.N642Lfs*10 and p.Y1111*. Expression analysis by western blotting and immunofluorescence microscopy revealed that the mutant alpha/beta-subunit precursor p.D76G is retained in the endoplasmic reticulum whereas the mutant p.S385L is correctly transported to the cis-Golgi apparatus and proteolytically processed. Both mutations lead to complete loss of GlcNAc-1-phosphotransferase activity, consistent with the severe clinical MLII phenotype of the patients. Our study expands the genotypic spectrum of MLII and provides novel insights into structural requirements to ensure GlcNAc-1-phosphotransferase activity.
- The Recurrent PPP1CB Mutation p. Pro49Arg in an Additional Noonan- Like Syndrome Individual: Broadening the Clinical Phenotype(2017) BERTOLA, Debora; YAMAMOTO, Guilherme; BUSCARILLI, Michelle; JORGE, Alexander; PASSOS-BUENO, Maria Rita; KIM, ChongWe report on a 12-year-old Brazilian boy with the p.Pro49Arg mutation in PPP1CB, a novel gene associated with RASopathies. This is the fifth individual described, and the fourth presenting the same variant, suggesting a mutational hotspot. Phenotypically, he also showed the same hair pattern-sparse, thin, and with slow growing-, similar to the typical ectodermal finding observed in Noonan syndrome-like disorder with loose anagen hair. Additionally, he presented craniosynostosis, a rare clinical finding in RASopathies. This report gives further support that this novel RASopathy-PPP1CB-related Noonan syndrome with loose anagen hair-shares great similarity to Noonan syndrome-like disorder with loose anagen hair, and expands the phenotypic spectrum by adding the cranial vault abnormality. (C) 2017 Wiley Periodicals, Inc.
conferenceObject GENOMIC APPROACHES TO INVESTIGATE CHILDREN BORN SMALL FOR GESTATIONAL AGE (SGA) WITHOUT CATCH UP-GROWTH(2017) HOMMA, Thais K.; FREIRE, Bruna; FUNARI, Mariana; MALAQUIAS, Alexsandra; RONJO, Rachel; VASQUES, Gabriela; CANTON, Ana; KIM, Chong; BERTOLA, Debora; JORGE, Alexander- 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.
- Mucopolysaccharidosis type I, II and VI and response to enzyme replacement therapy: Results from a single-center case series study(2017) FRANCO, J. F. S.; DIB, R. E. El; AGARWAL, A.; SOARES, D.; MILHAN, N. V. M.; ALBANO, L. M. J.; KIM, C. A.Mucopolysaccharidoses (MPS) types I, II and VI are associated with deficiencies in alpha- L-iduronidase, iduronate-2-sulfatase and N-acetylgalactosamine-4-sulfatase, respectively, and generally involve progressive and multi-systemic clinical manifestations. Enzyme replacement therapy (ERT) appears to be reasonably well tolerated. The aim of this study was to examine clinical and diagnostic findings of a series of pediatric and adult MPS patients, and assess the safety and efficacy of ERT in children and adults with MPS type I, II and VI. Pediatric and adult patients were treated weekly with 1 mg/kg recombinant human N-acetylgalactosamine-4-sulphatase (rhASB), 0.45 mg/kg alpha-L-iduronidase, or 0.5 mg/kg iduronate-2-sulfatase. Clinical and biochemical parameters with ERT were evaluated for a mean duration of 5 years. Mantel-Haenszel risk ratios and associated 95% confidence intervals (CIs) were calculated for rates of death among different types of enzyme replacement therapies (ERTs). Twenty-seven patients (mean ages - pediatric: 6.8 years; adult: 29 years) were included. ERT was found to be consistently well tolerated and effective in attenuating symptoms, but did not prevent the progression of the disease or reduce mortality rates. Our findings demonstrated that early diagnosis and initiation of ERT are critical for improvements in patient-important outcomes and quality of life, although disease progression and mortality rates remain high.
- Autosomal dominant frontometaphyseal dysplasia: Delineation of the clinical phenotype(2017) WADE, Emma M.; JENKINS, Zandra A.; DANIEL, Philip B.; MORGAN, Tim; ADDOR, Marie C.; ADES, Lesley C.; BERTOLA, Debora; BOHRING, Axel; CARTER, Erin; CHO, Tae-Joon; GEUS, Christa M. de; DUBA, Hans-Christoph; FLETCHER, Elaine; HADZSIEV, Kinga; HENNEKAM, Raoul C. M.; KIM, Chong A.; KRAKOW, Deborah; MORAVA, Eva; NEUHANN, Teresa; SILLENCE, David; SUPERTI-FURGA, Andrea; VEENSTRA-KNOL, Hermine E.; WIECZOREK, Dagmar; WILSON, Louise C.; MARKIE, David M.; ROBERTSON, Stephen P.Frontometaphyseal dysplasia (FMD) is caused by gain-of-function mutations in the X-linked gene FLNA in approximately 50% of patients. Recently we characterized an autosomal dominant form of FMD (AD-FMD) caused by mutations in MAP3K7, which accounts for the condition in the majority of patients who lack a FLNA mutation. We previously also described a patient with a de novo variant in TAB2, which we hypothesized was causative of another form of AD-FMD. In this study, a cohort of 20 individuals with AD-FMD is clinically evaluated. This cohort consists of 15 individuals with the recently described, recurrent mutation (c.1454C>T) in MAP3K7, as well as three individuals with missense mutations that result in substitutions in the N-terminal kinase domain of TGF beta-activated kinase 1 (TAK1), encoded by MAP3K7. Additionally, two individuals have missense variants in the gene TAB2, which encodes a protein with a close functional relationship to TAK1, TAK1-associated binding protein 2 (TAB2). Although the X-linked and autosomal dominant forms of FMD are very similar, there are distinctions to be made between the two conditions. Individuals with AD-FMD have characteristic facial features, and are more likely to be deaf, have scoliosis and cervical fusions, and have a cleft palate. Furthermore, there are features only found in AD-FMD in our review of the literature including valgus deformity of the feet and predisposition to keloid scarring. Finally, intellectual disability is present in a small number of subjects with AD-FMD but has not been described in association with X-linked FMD.