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
18 resultados
Resultados de Busca
Agora exibindo 1 - 10 de 18
conferenceObject Buccal cell whole exome sequencing improves the diagnostic yield in a Cornelia de Lange Syndrome Brazilian cohort(2024) NUNES, Beatriz Carvalho; FAVILLA, Bianca Pereira; VILELLA, Thaina; PINHEIRO, Isabel; AOI, Haromi; SEYAMA, Rie; MATSUMOTO, Naomichi; BELLUCCO, Fernanda Teixeira; KIM, Chong; MELARAGNO, Maria IsabelconferenceObject A 43 years-old patient with Cornelia de Lange Syndrome with NIPBL gene mutation and a mild phenotype(2024) VILELLA, Thaina; NUNES, Beatriz Carvalho; PINHEIRO, Isabel; AOI, Haromi; MATSUMOTO, Naomichi; KIM, Chong; MELARAGNO, Maria Isabel- De novo pathogenic DHX30 variants in two cases(2021) MIYAKE, Noriko; KIM, Chong Ae; HAGINOYA, Kazuhiro; CASTRO, Matheus Augusto Araujo; HONJO, Rachel Sayruri; MATSUMOTO, Naomichi
- Novel CLTC variants cause new brain and kidney phenotypes(2022) ITAI, Toshiyuki; MIYATAKE, Satoko; TSUCHIDA, Naomi; SAIDA, Ken; NARAHARA, Sho; TSUYUSAKI, Yu; CASTRO, Matheus Augusto Araujo; KIM, Chong Ae; OKAMOTO, Nobuhiko; UCHIYAMA, Yuri; KOSHIMIZU, Eriko; HAMANAKA, Kohei; FUJITA, Atsushi; MIZUGUCHI, Takeshi; MATSUMOTO, NaomichiHeterozygous variants in CLTC, which encode the clathrin heavy chain protein, cause neurodevelopmental delay of varying severity, and often accompanied by dysmorphic features, seizures, hypotonia, and ataxia. To date, 28 affected individuals with CLTC variants have been reported, although their phenotypes have not been fully elucidated. Here, we report three novel de novo CLTC (NM_001288653.1) variants in three individuals with previously unreported clinical symptoms: c.3662_3664del:p.(Leu1221del) in individual 1, c.2878T>C:p.(Trp960Arg) in individual 2, and c.2430+1G>T:p.(Glu769_Lys810del) in individual 3. Consistent with previous reports, individuals with missense or small in-frame variants were more severely affected. Unreported symptoms included a brain defect (cystic lesions along the lateral ventricles of the brain in individuals 1 and 3), kidney findings (high-echogenic kidneys in individual 1 and agenesis of the left kidney and right vesicoureteral reflux in individual 3), respiratory abnormality (recurrent pneumonia in individual 1), and abnormal hematological findings (anemia in individual 1 and pancytopenia in individual 3). Of note, individual 1 even exhibited prenatal abnormality (fetal growth restriction, cystic brain lesions, high-echogenic kidneys, and a heart defect), suggesting that CLTC variants should be considered when abnormal prenatal findings in multiple organs are detected.
- Brain monoamine vesicular transport disease caused by homozygous SLC18A2 variants: A study in 42 affected individuals(2023) SAIDA, Ken; MAROOTAIN, Reza; SENGOKU, Toru; MITANI, Tadahiro; PAGNAMENTA, Alistair T.; MARAFI, Dana; ZAKI, Maha S.; O'BRIAN, Thomas J.; KARIMIANI, Ehsan Ghayoor; KAIYRZHANOV, Rauan; TAKIZAWA, Marina; OHORI, Sachiko; LEONG, Huey Yin; AKAY, Gulsen; GALEHDARI, Hamid; ZAMANI, Mina; ROMY, Ratna; CARROLL, Christopher J.; TOOSI, Mehran Beiraghi; ASHRAFZADEH, Farah; IMANNEZHAD, Shima; MALEK, Hadis; AHANGARI, Najmeh; TOMOUM, Hoda; GOWDA, Vykuntaraju K.; SRINIVASAN, Varunvenkat M.; MURPHY, David; DOMINIK, Natalia; ELBENDARY, Hasnaa M.; RAFAT, Karima; YILMAZ, Sanem; KANMAZ, Seda; SERIN, Mine; KRISHNAKUMAR, Deepa; GARDHAM, Alice; MAW, Anna; RAO, Tekki Sreenivasa; ALSUBHI, Sarah; SROUR, Myriam; BUHAS, Daniela; JEWETT, Tamison; GOLDBERG, Rachel E.; SHAMSELDIN, Hanan; FRENGEN, Eirik; MISCEO, Doriana; STROMME, Petter; CERONI, Jose Ricardo Magliocco; KIM, Chong Ae; YESIL, Gozde; SENGENC, Esma; GULER, Serhat; HULL, Mariam; PARNES, Mered; AKTAS, Dilek; ANLAR, Banu; BAYRAM, Yavuz; PEHLIVAN, Davut; POSEY, Jennifer E.; ALAYI, Shahryar; MANSHADI, Seyed Ali Madani; ALZAIDAN, Hamad; AL-OWAIN, Mohammad; ALABDI, Lama; ABDULWAHAB, Ferdous; SEKIGUCHI, Futoshi; HAMANAKA, Kohei; FUJITA, Atsushi; UCHIYAMA, Yuri; MIZUGUCHI, Takeshi; MIYATAKE, Satoko; MIYAKE, Noriko; ELSHAFIE, Reem M.; SALAYEV, Kamran; GULIYEVA, Ulviyya; ALKURAYA, Fowzan S.; GLEESON, Joseph G.; MONAGHAN, Kristin G.; LANGLEY, Katherine G.; YANG, Hui; MOTAVAF, Mahsa; SAFARI, Saeid; ALIPOUR, Mozhgan; OGATA, Kazuhiro; BROWN, Andre E. X.; LUPSKI, James R.; HOULDEN, Henry; MATSUMOTO, NaomichiPurpose: Brain monoamine vesicular transport disease is an infantile-onset movement disorder that mimics cerebral palsy. In 2013, the homozygous SLC18A2 variant, p.Pro387Leu, was first reported as a cause of this rare disorder, and dopamine agonists were efficient for treating affected individuals from a single large family. To date, only 6 variants have been reported. In this study, we evaluated genotype-phenotype correlations in individuals with biallelic SLC18A2 variants.Methods: A total of 42 affected individuals with homozygous SLC18A2 variant alleles were identified. We evaluated genotype-phenotype correlations and the missense variants in the affected individuals based on the structural modeling of rat VMAT2 encoded by Slc18a2, with cytoplasm-and lumen-facing conformations. A Caenorhabditis elegans model was created for functional studies.Results: A total of 19 homozygous SLC18A2 variants, including 3 recurrent variants, were identified using exome sequencing. The affected individuals typically showed global develop-mental delay, hypotonia, dystonia, oculogyric crisis, and autonomic nervous system involve-ment (temperature dysregulation/sweating, hypersalivation, and gastrointestinal dysmotility). Among the 58 affected individuals described to date, 16 (28%) died before the age of 13 years. Of the 17 patients with p.Pro237His, 9 died, whereas all 14 patients with p.Pro387Leu survived. Although a dopamine agonist mildly improved the disease symptoms in 18 of 21 patients (86%), some affected individuals with p.Ile43Phe and p.Pro387Leu showed milder phenotypes and presented prolonged survival even without treatment. The C. elegans model showed behavioral abnormalities. Conclusion: These data expand the phenotypic and genotypic spectra of SLC18A2-related disorders.(c) 2022 American College of Medical Genetics and Genomics.
- Phenotypic and mutational spectrum of ROR2-related Robinow syndrome(2022) LIMA, Ariadne R.; FERREIRA, Barbara M.; ZHANG, Chaofan; JOLLY, Angad; DU, Haowei; WHITE, Janson J.; DAWOOD, Moez; LINS, Tulio C.; CHIABAI, Marcela A.; BEUSEKOM, Ellen; CORDOBA, Mara S.; ROSA, Erica C. C. Caldas; KAYSERILI, Hulya; KIMONIS, Virginia; WU, Erica; MELLADO, Cecilia; AGGARWAL, Vineet; RICHIERI-COSTA, Antonio; BRUNONI, Decio; CANO, Talyta M.; JORGE, Alexander A. L.; KIM, Chong A.; HONJO, Rachel; BERTOLA, Debora R.; DANDALO-GIRARDI, Raissa M.; BAYRAM, Yavuz; GEZDIRICI, Alper; YILMAZ-GULEC, Elif; GUMUS, Evren; YILMAZ, Gulay C.; OKAMOTO, Nobuhiko; OHASHI, Hirofumi; COBAN-AKDEMIR, Zeynep; MITANI, Tadahiro; JHANGIANI, Shalini N.; MUZNY, Donna M.; REGATTIERI, Neysa A. P.; POGUE, Robert; PEREIRA, Rinaldo W.; OTTO, Paulo A.; GIBBS, Richard A.; ALI, Bassam R.; BOKHOVEN, Hans; BRUNNER, Han G.; SUTTON, V. Reid; LUPSKI, James R.; VIANNA-MORGANTE, Angela M.; CARVALHO, Claudia M. B.; MAZZEU, Juliana F.Robinow syndrome is characterized by a triad of craniofacial dysmorphisms, disproportionate-limb short stature, and genital hypoplasia. A significant degree of phenotypic variability seems to correlate with different genes/loci. Disturbances of the noncanonical WNT-pathway have been identified as the main cause of the syndrome. Biallelic variants in ROR2 cause an autosomal recessive form of the syndrome with distinctive skeletal findings. Twenty-two patients with a clinical diagnosis of autosomal recessive Robinow syndrome were screened for variants in ROR2 using multiple molecular approaches. We identified 25 putatively pathogenic ROR2 variants, 16 novel, including single nucleotide variants and exonic deletions. Detailed phenotypic analyses revealed that all subjects presented with a prominent forehead, hypertelorism, short nose, abnormality of the nasal tip, brachydactyly, mesomelic limb shortening, short stature, and genital hypoplasia in male patients. A total of 19 clinical features were present in more than 75% of the subjects, thus pointing to an overall uniformity of the phenotype. Disease-causing variants in ROR2, contribute to a clinically recognizable autosomal recessive trait phenotype with multiple skeletal defects. A comprehensive quantitative clinical evaluation of this cohort delineated the phenotypic spectrum of ROR2-related Robinow syndrome. The identification of exonic deletion variant alleles further supports the contention of a loss-of-function mechanism in the etiology of the syndrome.
- Pathogenic variants detected by RNA sequencing in Cornelia de Lange syndrome(2022) SEYAMA, Rie; UCHIYAMA, Yuri; CERONI, Jose Ricard Magliocco; KIM, Veronica Eun Hue; FURQUIM, Isabel; HONJO, Rachel Sayuri; CASTRO, Matheus Augusto Araujo; PIRES, Lucas Vieira Lacerda; AOI, Hiromi; IWAMA, Kazuhiro; HAMANAKA, Kohei; FUJITA, Atsushi; TSUCHIDA, Naomi; KOSHIMIZU, Eriko; MISAWA, Kazuharu; MIYATAKE, Satoko; MIZUGUCHI, Takeshi; MAKINO, Shintaro; ITAKURA, Atsuo; BERTOLA, Debora R.; KIM, Chong Ae; MATSUMOTO, NaomichiRecent studies suggest that transcript isoforms significantly overlap (approximately 60%) between brain tissue and Epstein-Barr virus-transformed lymphoblastoid cell lines (LCLs). Interestingly, 14 cohesion-related genes with variants that cause Cornelia de Lange Syndrome (CdLS) are highly expressed in the brain and LCLs. In this context, we first performed RNA sequencing of LCLs from 22 solved (with pathogenic variants) and 19 unsolved (with no confirmed variants) CdLS cases. Next, an RNA sequencing pipeline was developed using solved cases with two different methods: short variant analysis (for single-nucleotide and indel variants) and aberrant splicing detection analysis. Then, 19 unsolved cases were subsequently applied to our pipeline, and four pathogenic variants in NIPBL (one inframe deletion and three intronic variants) were newly identified. Two of three intronic variants were located at Alu elements in deep-intronic regions, creating cryptic exons. RNA sequencing with LCLs was useful for identifying hidden variants in exome-negative cases.
- Hemorrhagic stroke and renovascular hypertension with Grange syndrome arising from a novel pathogenic variant in YY1AP1(2019) SAIDA, Ken; KIM, Chong Ae; CERONI, Jose Ricardo Magliocco; BERTOLA, Debora Romeo; HONJO, Rachel Sayuri; MITSUHASHI, Satomi; TAKATA, Atsushi; MIZUGUCHI, Takeshi; MIYATAKE, Satoko; MIYAKE, Noriko; MATSUMOTO, NaomichiPediatric hypertension can cause hypertensive emergencies, including hemorrhagic stroke, contributing to rare but serious childhood morbidity and mortality. Renovascular hypertension (RVH) is one of the major causes of secondary hypertension in children. Grange syndrome (MIM#602531) is a rare disease characterized by multiple stenosis or occlusion of the renal, abdominal, coronary, and cerebral arteries, which can cause phenotypes of RVH and fibromuscular dysplasia (MIM#135580). We report the case of a 7-year-old girl with Grange syndrome who showed RVH and multiple seizure episodes. At 1 year of age, she experienced seizures and sequential hemiparesis caused by a left thalamic hemorrhage without cerebral vascular anomalies. Chronic hypertension was observed, and abdominal computed tomography angiography showed characteristic bilateral renal artery stenosis. Whole-exome sequencing revealed a novel homozygous pathogenic variant in the YY1AP1 gene (NM_001198903.1: c.1169del: p.Lys390Argfs*12). Biallelic YY1AP1 mutations are known to cause Grange syndrome. Unlike previously reported patients, our patient presented with intracerebral hemorrhagic stroke without anomalous brain artery or bone fragility. The phenotype in our patient may help better understand this ultrarare syndrome. Grange syndrome should be considered in patients presenting with childhood-onset hypertension and/or hemorrhagic stroke for early clinical intervention.
- Cerebellofaciodental syndrome in an adult patient: Expanding the phenotypic and natural history characteristics(2021) HONJO, Rachel Sayuri; CASTRO, Matheus Augusto Araujo; FERRACIOLLI, Suely Fazio; SOARES JUNIOR, Luiz Alberto Valente; PASTORINO, Antonio Carlos; BERTOLA, Debora Romeo; MIYAKE, Noriko; MATSUMOTO, Naomichi; KIM, Chong AeCerebellofaciodental syndrome is characterized by facial dysmorphisms, intellectual disability, cerebellar hypoplasia, and dental anomalies. It is an autosomal-recessive condition described in 2015 caused by pathogenic variants in BRF1. Here, we report a Brazilian patient who faced a diagnostic challenge beginning at 11 months of age. Fortunately, whole-exome sequencing (WES) was performed, detecting the BRF1 variants NM_001519.3:c.1649delG:p.(Gly550Alafs*36) and c.421C>T:p.(Arg141Cys) in compound heterozygosity, thus finally achieving a diagnosis of cerebellofaciodental syndrome. The patient is currently 25 years old and is the oldest patient yet reported. The clinical report and a review of published cases are presented. Atlanto-occipital fusion, a reduced foramen magnum and basilar invagination leading to compression of the medulla-spinal cord transition are skeletal findings not reported in previous cases. The description of syndromes with dental findings shows that such anomalies can be an important clue to relevant differential diagnoses. The cooperation of groups from different international centers made possible the resolution of this and other cases and is one of the strategies to bring medical advances to developing countries, where many patients with rare diseases are difficult to diagnose definitively.
- Imagawa-Matsumoto syndrome: SUZ12-related overgrowth disorder(2023) IMAGAWA, Eri; SEYAMA, Rie; AOI, Hiromi; UCHIYAMA, Yuri; MARCARINI, Bruno Guimaraes; FURQUIM, Isabel; HONJO, Rachel Sayuri; BERTOLA, Debora Romeo; KIM, Chong Ae; MATSUMOTO, NaomichiThe SUZ12 gene encodes a subunit of polycomb repressive complex 2 (PRC2) that is essential for development by silencing the expression of multiple genes. Germline heterozygous variants in SUZ12 have been found in Imagawa-Matsumoto syndrome (IMMAS) characterized by overgrowth and multiple dysmorphic features. Similarly, both EZH2 and EED also encode a subunit of PRC2 each and their pathogenic variants cause Weaver syndrome and Cohen-Gibson syndrome, respectively. Clinical manifestations of these syndromes significantly overlap, although their different prevalence rates have recently been noted: generalized overgrowth, intellectual disability, scoliosis, and excessive loose skin appear to be less prevalent in IMMAS than in the other two syndromes. We could not determine any apparent genotype-phenotype correlation in IMMAS. The phenotype of neurofibromatosis type 1 arising from NF1 deletion was also shown to be modified by the deletion of SUZ12, 560 kb away. This review deepens our understanding of the clinical and genetic characteristics of IMMAS together with other overgrowth syndromes related to PRC2. We also report on a novel IMMAS patient carrying a splicing variant (c.1023+1G>C) in SUZ12. This patient had a milder phenotype than other previously reported IMMAS cases, with no macrocephaly or overgrowth phenotypes, highlighting the clinical variation in IMMAS.