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1.
Stem Cell Res ; 76: 103324, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38301425

RESUMO

Sotos syndrome (SoS) is a neurodevelopmental disorder that results from NSD1 mutations that cause haploinsufficiency of NSD1. Here, we generated an induced pluripotent stem cell (iPSC) line from fibroblasts of a SoS patient carrying the pathogenic variant (c.1633delA). The cell line shows typical iPSC morphology, high expression of pluripotent markers, normal karyotype, and it differentiates into three germ layers in vitro. This line is a valuable resource for studying pathological pathways involved in SoS.


Assuntos
Craniossinostoses , Células-Tronco Pluripotentes Induzidas , Deficiência Intelectual , Síndrome de Sotos , Humanos , Síndrome de Sotos/genética , Síndrome de Sotos/metabolismo , Síndrome de Sotos/patologia , Células-Tronco Pluripotentes Induzidas/metabolismo , Mutação , Éxons , Histona-Lisina N-Metiltransferase/genética
2.
Am J Med Genet A ; 191(7): 1836-1848, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37066965

RESUMO

Sotos syndrome (SoS) is a congenital overgrowth syndrome with variable degree of intellectual disability caused in the 90% of cases by pathogenetic variants of the Nuclear receptor binding SET Domain protein1 (NSD1) gene. NSD1 gene functions can be abrogated by different genetic alterations (i.e., small intragenic pathogenic variants like deletions/insertions, nonsense/missense pathogenic variants, partial gene deletions and whole deletions or microdeletion of 5q35 chromosomal region). Therefore, correlation of the genotype-phenotype with a possible contribution of more implicated genes to the medical, cognitive and behavioral profile is a topic of great interest. Although a more severe learning disability has been described in individuals with 5q35 microdeletion when compared to individuals with NSD1 intragenic pathogenic variants a fully delineated cognitive and behavioral phenotype has not been described yet. The importance of providing clinical characterization in relation to the genotype comes from the necessity to early identify children more at risk of developing psychopathological disorders. We characterize the cognitive, adaptive and behavioral phenotype of a pediatric sample of 64 individuals affected by SoS, performing a standardized neuropsychological evaluation. Secondly, we compare cognitive-behavioral profiles of SoS individuals carrying and not carrying the 5q35 microdeletion. SoS participants were characterized by a mild cognitive impairment of both Intellectual Quotient and adaptive skills in association to borderline symptoms of attention deficit. Our results suggest that the 5q35 microdeletion is associated with lower scores specifically concerning the cognitive, adaptive functioning and behavioral domains. However, longitudinal studies are necessary to confirm these findings and delineate a developmental trajectory of SoS.


Assuntos
Síndrome de Sotos , Humanos , Síndrome de Sotos/patologia , Histona-Lisina N-Metiltransferase/genética , Histona Metiltransferases/genética , Fenótipo , Cognição
3.
Appl Biochem Biotechnol ; 195(10): 5792-5801, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36708490

RESUMO

This study is to identify the pathogenic mutation of a child with Sots syndrome and provide prenatal diagnosis for his pregnant mother. Chromosome microarray technology was used to detect whether there were minor deletions/duplication in patients' chromosomes. The gene mutation of patients was screened by next-generation sequencing technology, and it was verified by Sanger sequencing. Prenatal diagnosis of the fetus was conducted according to the selected pathogenic sites, and genetic counseling was conducted for her parents. Chromosome microarray results showed that there was no minor deletion in a chromosome 5q35 region, and the second-generation sequencing results showed that there was a c.4138delG heterozygous mutation in the patient's NSD1 gene, and the pathogenic of this mutation was not reported in related databases. Sanger sequencing found that there was a c.4138delG heterozygous mutation in the NSD1 gene of the patient and her parents' genotype at this locus was wild type. The prenatal gene test results indicated that there was heterozygous mutation of NSD1 gene c.4138delG in the fetus, so it was suggested to terminate the pregnancy. Gentling results indicated that the fetus and the patient inherited the same maternal chromosome 5. The heterozygous mutation of NSD1 gene c.4138delG is the pathogenic mutation of this Sots syndrome patient, and the mother may be germinal mosaicism.


Assuntos
Síndrome de Sotos , Humanos , Criança , Feminino , Síndrome de Sotos/diagnóstico , Síndrome de Sotos/genética , Síndrome de Sotos/patologia , Histona-Lisina N-Metiltransferase/genética , Histona Metiltransferases/genética , Mães , Mosaicismo , Fenótipo
4.
Stem Cell Res ; 66: 103007, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36580887

RESUMO

Sotos syndrome (SoS) is a neurodevelopmental disorder caused by haploinsufficiency of the NSD1 gene located on chromosome 5 region q35.3. In order to understand the pathogenesis of Sotos syndrome and in view of future therapeutic approaches for its efficient treatment, we generated two human induced pluripotent stem cells (iPSCs) lines from one SoS patient carrying a 5q35 microdeletion. The established iPSCs expressed pluripotency markers, showing the capacity to differentiate into the three germ layers.


Assuntos
Células-Tronco Pluripotentes Induzidas , Síndrome de Sotos , Humanos , Síndrome de Sotos/genética , Síndrome de Sotos/patologia , Células-Tronco Pluripotentes Induzidas/patologia , Histona Metiltransferases/genética , Histona-Lisina N-Metiltransferase/genética , Haploinsuficiência
5.
Gene ; 851: 146970, 2023 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-36261088

RESUMO

NSD1 gene (Nuclear Receptor Binding SET Domain Protein 1) encodes a methyltransferase that plays an important role in embryonic development. NSD1 is implicated in the transcription and methylation of histone H3 at lysine 36 (H3-K36), but the molecular mechanisms involved in these processes remain largely unknown. Pathogenic variants of NSD1 gene lead to Sotos syndrome, and have also been detected in some type of cancers, such as acute myeloid leukemia. In this study we have investigated NSD1 mRNA expression in fibroblast cell lines obtained from 14 Sotos patients and from 8 healthy controls. In addition to the expected NSD1 canonical transcript (isoform 1), we identified two additional, not yet reported, short NSD1 mRNA isoforms: NSD1 Δ5Δ7 (isoform 2) and NSD1 Δ19-23 (isoform 3), both in healthy subjects and in Sotos patients. We also show that NSD1 mutations in patients can be associated with a decreased level of NSD1 mRNA, as expected. Moreover, one patient, bearing the NSD1 variant c.6010-10G > A, expressed an additional shorter transcript derived from an aberrant splicing event. These results may provide a basis to elucidate the impact of different NSD1 pathogenic variants on the heterogeneity of phenotype associated with Sotos syndrome.


Assuntos
Síndrome de Sotos , Humanos , Síndrome de Sotos/genética , Síndrome de Sotos/patologia , Histona Metiltransferases , Voluntários Saudáveis , Proteínas Nucleares/metabolismo , Peptídeos e Proteínas de Sinalização Intracelular/genética , RNA Mensageiro/genética , Histona-Lisina N-Metiltransferase/genética
6.
Genes (Basel) ; 13(11)2022 11 19.
Artigo em Inglês | MEDLINE | ID: mdl-36421837

RESUMO

BACKGROUND: Inactivating NSD1 mutations causing Sotos syndrome have been previously associated with a specific genome-wide DNA methylation (DNAm) pattern. Sotos syndrome is characterized by phenotypic overlap with other overgrowth syndromes, and a definite diagnosis might not be easily reached due to the high prevalence of variants of unknown significance (VoUS) that are identified in patients with a suggestive phenotype. OBJECTIVE: we performed microarray DNAm profiling in a set of 11 individuals with a clinical suspicion of Sotos syndrome and carrying an NSD1 VoUS or previously unreported variants to solve uncertainty in defining pathogenicity of the observed variants. The impact of the training cohort size on sensitivity and prediction confidence of the classifier was assessed. RESULTS: The Sotos syndrome-specific DNAm signature was validated in six individuals with a clinical diagnosis of Sotos syndrome and carrying bona fide pathogenic NSD1 variants. Applying this approach to the remaining 11 individuals with NSD1 variants, we succeeded in confirming pathogenicity in eight subjects and excluding the diagnosis of Sotos syndrome in three. The sensitivity and prediction confidence of the classifier based on the different sizes of the training sets did not show substantial differences, though the overall performance was improved by using a data balancing strategy. CONCLUSIONS: The present approach solved uncertainty in cases with NDS1 VoUS, further demonstrating the clinical utility of DNAm profiling.


Assuntos
Síndrome de Sotos , Humanos , Síndrome de Sotos/diagnóstico , Síndrome de Sotos/genética , Síndrome de Sotos/patologia , Metilação de DNA/genética , Histona-Lisina N-Metiltransferase/genética , Incerteza , Transtornos do Crescimento/genética , Transtornos do Crescimento/patologia
7.
Am J Med Genet A ; 185(2): 549-554, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33191647

RESUMO

Silver-Russell syndrome (SRS) is characterized by pre- and postnatal growth deficiency. It is most often caused by hypomethylation of the paternal imprinting center 1 of chromosome 11p15.5. In contrast, Sotos syndrome is an overgrowth syndrome that results either from pathogenic NSD1 gene variants or copy number variations affecting the NSD1 gene. Here, we report on a 6 month-old boy with severe short stature, relative macrocephaly, severe feeding difficulties with underweight, muscular hypotonia, motor delay, medullary nephrocalcinosis, bilateral sensorineural hearing impairment and facial dysmorphisms. SNP array revealed a 2.1 Mb de novo interstitial deletion of 5q35.2q35.3 encompassing the NSD1 gene. As Sotos syndrome could not satisfactorily explain his symptoms, diagnostic testing for SRS was initiated. It demonstrated hypomethylation of the imprinting center 1 of chromosome 11p15.5 confirming the clinically suspected SRS. We compared the symptoms of our patient with the typical clinical features of individuals with SRS and Sotos syndrome, respectively. To our knowledge, this is the first study reporting the very unusual coincidence of both Sotos syndrome and SRS in the same patient.


Assuntos
Histona-Lisina N-Metiltransferase/genética , Síndrome de Silver-Russell/genética , Síndrome de Sotos/genética , Deleção Cromossômica , Cromossomos Humanos Par 5/genética , Variações do Número de Cópias de DNA/genética , Metilação de DNA/genética , Impressão Genômica/genética , Humanos , Lactente , Recém-Nascido , Masculino , Fenótipo , Polimorfismo de Nucleotídeo Único/genética , Síndrome de Silver-Russell/complicações , Síndrome de Silver-Russell/diagnóstico , Síndrome de Silver-Russell/patologia , Síndrome de Sotos/complicações , Síndrome de Sotos/diagnóstico , Síndrome de Sotos/patologia
8.
Am J Med Genet A ; 182(9): 2181-2183, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32677741

RESUMO

Sotos syndrome is one of the overgrowth syndromes, and can present with intellectual disability, behavioral problems and tall stature. In some cases, seizures, pectus deformity, cardiac and renal anomalies may be identified. Here we report two Indian children with Sotos syndrome whose initial presentation was macrocephaly and behavioral problems, respectively. The pathogenic variants in NSD1 gene were confirmed by next generation sequencing. The gene variants in the two children, one male and one female; were NSD1: c.2362C>T and NSD1: c.5474dup, respectively, leading to premature termination of protein formation.


Assuntos
Histona-Lisina N-Metiltransferase/genética , Deficiência Intelectual/genética , Síndrome de Sotos/genética , Povo Asiático/genética , Pré-Escolar , Feminino , Humanos , Índia/epidemiologia , Lactente , Deficiência Intelectual/patologia , Masculino , Mutação , Fenótipo , Síndrome de Sotos/patologia
10.
Genes Brain Behav ; 19(4): e12637, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-31909872

RESUMO

Sotos syndrome is a developmental disorder characterized by a suite of clinical features. In children, the three cardinal features of Sotos syndrome are a characteristic facial appearance, learning disability and overgrowth (height and/or head circumference > 2 SDs above average). These features are also evident in adults with this syndrome. Over 90% of Sotos syndrome patients are haploinsufficient for the gene encoding nuclear receptor-binding Su(var)3-9, Enhancer-of-zesteand Trithorax domain-containing protein 1 (NSD1). NSD1 is a histone methyltransferase that catalyzes the methylation of lysine residue 36 on histone H3. However, although the symptomology of Sotos syndrome is well established, many aspects of NSD1 biology remain unknown. Here, we assessed the expression of Nsd1 within the mouse brain, and showed a predominantly neuronal pattern of expression for this histone-modifying factor. We also generated a mouse strain lacking one allele of Nsd1 and analyzed morphological and behavioral characteristics in these mice, showing behavioral characteristics reminiscent of some of the deficits seen in Sotos syndrome patients.


Assuntos
Córtex Cerebral/patologia , Histona-Lisina N-Metiltransferase/genética , Síndrome de Sotos/genética , Animais , Córtex Cerebral/metabolismo , Feminino , Heterozigoto , Histona-Lisina N-Metiltransferase/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Neurônios/metabolismo , Síndrome de Sotos/patologia
11.
Nat Rev Endocrinol ; 15(5): 299-311, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30842651

RESUMO

Overgrowth syndromes are a heterogeneous group of rare disorders characterized by generalized or segmental excessive growth commonly associated with additional features, such as visceromegaly, macrocephaly and a large range of various symptoms. These syndromes are caused by either genetic or epigenetic anomalies affecting factors involved in cell proliferation and/or the regulation of epigenetic markers. Some of these conditions are associated with neurological anomalies, such as cognitive impairment or autism. Overgrowth syndromes are frequently associated with an increased risk of cancer (embryonic tumours during infancy or carcinomas during adulthood), but with a highly variable prevalence. Given this risk, syndrome-specific tumour screening protocols have recently been established for some of these conditions. Certain specific clinical traits make it possible to discriminate between different syndromes and orient molecular explorations to determine which molecular tests to conduct, despite the syndromes having overlapping clinical features. Recent advances in molecular techniques using next-generation sequencing approaches have increased the number of patients with an identified molecular defect (especially patients with segmental overgrowth). This Review discusses the clinical and molecular diagnosis, tumour risk and recommendations for tumour screening for the most prevalent generalized and segmental overgrowth syndromes.


Assuntos
Neoplasias/epidemiologia , Neoplasias/genética , Arritmias Cardíacas/epidemiologia , Arritmias Cardíacas/genética , Arritmias Cardíacas/patologia , Feminino , Doenças Genéticas Ligadas ao Cromossomo X/epidemiologia , Doenças Genéticas Ligadas ao Cromossomo X/genética , Doenças Genéticas Ligadas ao Cromossomo X/patologia , Gigantismo/epidemiologia , Gigantismo/genética , Gigantismo/patologia , Cardiopatias Congênitas/epidemiologia , Cardiopatias Congênitas/genética , Cardiopatias Congênitas/patologia , Humanos , Deficiência Intelectual/epidemiologia , Deficiência Intelectual/genética , Deficiência Intelectual/patologia , Megalencefalia/epidemiologia , Megalencefalia/genética , Megalencefalia/patologia , Neoplasias/patologia , Gravidez , Fatores de Risco , Síndrome de Sotos/epidemiologia , Síndrome de Sotos/genética , Síndrome de Sotos/patologia , Síndrome
12.
Horm Res Paediatr ; 92(1): 64-70, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30879005

RESUMO

Initially described as an uncommon presenting feature of Sotos syndrome (SoS), over the last decades, congenital hyperinsulinaemic hypoglycaemia (CHI) has been increasingly reported in association with this condition. The mechanism responsible for CHI in SoS is unclear. We report the case of a neonate presenting with CHI and extensive venous and arterial thrombosis associated with kidney, heart, liver, skeleton, and brain abnormalities and finally diagnosed with SoS on whole genome sequencing. Our case describes an extended phenotype associated with SoS presenting with CHI (including thrombosis and liver dysfunction) and reinforces the association of transient CHI with SoS. The case also shows that an early neonatal diagnosis of rare genetic conditions is challenging, especially in acutely unwell patients, and that in complex cases with incomplete, atypical, or overlapping phenotypes, broad genomic testing by whole exome or whole genome sequencing may be a useful diagnostic strategy.


Assuntos
Hiperinsulinismo , Hipoglicemia , Doenças do Recém-Nascido , Síndrome de Sotos , Trombose , Humanos , Hiperinsulinismo/genética , Hiperinsulinismo/metabolismo , Hiperinsulinismo/patologia , Hipoglicemia/metabolismo , Hipoglicemia/patologia , Recém-Nascido , Doenças do Recém-Nascido/genética , Doenças do Recém-Nascido/metabolismo , Doenças do Recém-Nascido/patologia , Masculino , Síndrome de Sotos/genética , Síndrome de Sotos/metabolismo , Síndrome de Sotos/patologia , Trombose/genética , Trombose/metabolismo , Trombose/patologia , Sequenciamento Completo do Genoma
13.
Am J Med Genet A ; 179(4): 542-551, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30719864

RESUMO

Sotos syndrome is an overgrowth syndrome characterized by distinctive facial features and intellectual disability caused by haploinsufficiency of the NSD1 gene. Genotype-phenotype correlations have been observed, with major anomalies seen more frequently in patients with 5q35 deletions than those with point mutations in NSD1. Though endocrine features have rarely been described, transient hyperinsulinemic hypoglycemia (HI) of the neonatal period has been reported as an uncommon presentation of Sotos syndrome. Eight cases of 5q35 deletions and one patient with an intragenic NSD1 mutation with transient HI have been reported. Here, we describe seven individuals with HI caused by NSD1 gene mutations with three having persistent hyperinsulinemic hypoglycemia. These patients with persistent HI and Sotos syndrome caused by NSD1 mutations, further dispel the hypothesis that HI is due to the deletion of other genes in the deleted 5q35 region. These patients emphasize that NSD1 haploinsufficiency is sufficient to cause HI, and suggest that Sotos syndrome should be considered in patients presenting with neonatal HI. Lastly, these patients help extend the phenotypic spectrum of Sotos syndrome to include HI as a significant feature.


Assuntos
Hiperinsulinismo Congênito/patologia , Deficiências do Desenvolvimento/patologia , Transtornos do Crescimento/patologia , Histona-Lisina N-Metiltransferase/genética , Mutação , Síndrome de Sotos/patologia , Adulto , Hiperinsulinismo Congênito/genética , Deficiências do Desenvolvimento/genética , Feminino , Transtornos do Crescimento/genética , Humanos , Lactente , Recém-Nascido , Masculino , Fenótipo , Prognóstico , Síndrome de Sotos/genética
14.
Clin Cancer Res ; 23(12): e83-e90, 2017 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-28620009

RESUMO

In October 2016, the American Association for Cancer Research held a meeting of international childhood cancer predisposition syndrome experts to evaluate the current knowledge of these syndromes and to propose consensus surveillance recommendations. Herein, we summarize clinical and genetic aspects of RASopathies and Sotos, Weaver, Rubinstein-Taybi, Schinzel-Giedion, and NKX2-1 syndromes as well as specific metabolic disorders known to be associated with increased childhood cancer risk. In addition, the expert panel reviewed whether sufficient data exist to make a recommendation that all patients with these disorders be offered cancer surveillance. For all syndromes, the panel recommends increased awareness and prompt assessment of clinical symptoms. Patients with Costello syndrome have the highest cancer risk, and cancer surveillance should be considered. Regular physical examinations and complete blood counts can be performed in infants with Noonan syndrome if specific PTPN11 or KRAS mutations are present, and in patients with CBL syndrome. Also, the high brain tumor risk in patients with L-2 hydroxyglutaric aciduria may warrant regular screening with brain MRIs. For most syndromes, surveillance may be needed for nonmalignant health problems. Clin Cancer Res; 23(12); e83-e90. ©2017 AACRSee all articles in the online-only CCR Pediatric Oncology Series.


Assuntos
Anormalidades Múltiplas/epidemiologia , Hipotireoidismo Congênito/epidemiologia , Anormalidades Craniofaciais/epidemiologia , Deformidades Congênitas da Mão/epidemiologia , Deficiência Intelectual/epidemiologia , Unhas Malformadas/epidemiologia , Síndrome de Rubinstein-Taybi/epidemiologia , Síndrome de Sotos/epidemiologia , Anormalidades Múltiplas/genética , Anormalidades Múltiplas/patologia , Neoplasias Encefálicas/epidemiologia , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patologia , Neoplasias Colorretais/epidemiologia , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Hipotireoidismo Congênito/genética , Hipotireoidismo Congênito/patologia , Síndrome de Costello/epidemiologia , Síndrome de Costello/genética , Síndrome de Costello/patologia , Anormalidades Craniofaciais/genética , Anormalidades Craniofaciais/patologia , Deformidades Congênitas da Mão/genética , Deformidades Congênitas da Mão/patologia , Humanos , Deficiência Intelectual/genética , Deficiência Intelectual/patologia , Mutação , Unhas Malformadas/genética , Unhas Malformadas/patologia , Síndromes Neoplásicas Hereditárias/epidemiologia , Síndromes Neoplásicas Hereditárias/genética , Síndromes Neoplásicas Hereditárias/patologia , Síndrome de Noonan/epidemiologia , Síndrome de Noonan/genética , Síndrome de Noonan/patologia , Proteína Tirosina Fosfatase não Receptora Tipo 11/genética , Fatores de Risco , Síndrome de Rubinstein-Taybi/genética , Síndrome de Rubinstein-Taybi/patologia , Síndrome de Sotos/genética , Síndrome de Sotos/patologia , Fator Nuclear 1 de Tireoide/genética
15.
Genet Couns ; 26(1): 1-12, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26043501

RESUMO

Sotos syndrome is a well-known overgrowth syndrome characterized by excessive growth during childhood, macrocephaly, distinctive facial appearance and learning disability. This disorder is caused by mutations or deletions in NSD1 gene. The aim of this study is to examine the relationship between the neuroimaging and clinical features of children with Sotos syndrome. Six Turkish children with Sotos syndrome were followed up about 3-7 years. The diagnosis was confirmed with molecular genetic analysis. We identified the pathogenic NSD1 mutation including three novel in all patients. All the patients had a characteristic facial gestalt of Sotos syndrome consisting of triangular face with prominent forehead, frontoparietal sparseness of hair and small nose. However, the degree of psychomotor and intellectual development was variable. Severe learning defect and speech delay were remarkable in two patients. The neuroimaging analysis showed abnormalities in four of six patients including bilateral large ventricles, thinning of the corpus callosum and persistent cavum septum pellucidum et vergae. Typical craniofacial appearance is the primary finding for the diagnosis of the disease even in the infantile period. However, the degree of psychomotor and intellectual development is very variable and does not correlate with the neuroimaging findings.


Assuntos
Anormalidades Craniofaciais/genética , Peptídeos e Proteínas de Sinalização Intracelular/genética , Proteínas Nucleares/genética , Síndrome de Sotos , Criança , Pré-Escolar , Anormalidades Craniofaciais/patologia , Feminino , Seguimentos , Histona Metiltransferases , Histona-Lisina N-Metiltransferase , Humanos , Masculino , Síndrome de Sotos/genética , Síndrome de Sotos/patologia , Síndrome de Sotos/fisiopatologia , Turquia
17.
Acta Cytol ; 57(2): 213-20, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23406665

RESUMO

BACKGROUND: Ectopic cervical thymomas are rare and there are few descriptions of the cytologic findings based on fine needle aspiration. Their appearances can be misinterpreted as either benign or malignant lesions of the thyroid. The authors report such a case occurring in a patient with Sotos syndrome, a genetic disorder characterized by somatic overgrowth and cognitive impairment. CASE REPORT: The patient developed a neck mass that was examined first by fine needle aspiration and then by pathologic examination of the resected specimen. On fine needle aspiration, a diagnosis of papillary carcinoma of the thyroid was favoured, based on the presence of large cohesive sheets of anastomosing papillary tissue fragments with fibrovascular cores. Pathologic examination of the resection specimen showed a thymoma, subtype B3. The cytologic findings correlated with the presence of nuclear palisading of tumour cells around perivascular spaces. CONCLUSION: To the best of our knowledge, this histologic subtype of thymoma has never been reported in ectopic cervical thymic tissue, nor these particular cytologic findings that can lead to an erroneous diagnosis of thyroid carcinoma. Moreover, this is the first description of thymoma in association with Sotos syndrome.


Assuntos
Biópsia por Agulha Fina , Carcinoma/patologia , Coristoma/patologia , Doenças do Mediastino/patologia , Neoplasias Epiteliais e Glandulares/patologia , Timo , Neoplasias do Timo/patologia , Neoplasias da Glândula Tireoide/patologia , Adulto , Idoso , Biomarcadores Tumorais/análise , Carcinoma Papilar , Diagnóstico Diferencial , Feminino , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Pescoço , Neoplasias Epiteliais e Glandulares/química , Neoplasias Epiteliais e Glandulares/terapia , Valor Preditivo dos Testes , Síndrome de Sotos/patologia , Neoplasias do Timo/química , Neoplasias do Timo/terapia , Câncer Papilífero da Tireoide
18.
J Hum Genet ; 58(2): 73-7, 2013 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-23190751

RESUMO

Sotos syndrome is an overgrowth syndrome with characteristic facial dysmorphism, variable severity of learning disabilities and macrocephaly with overgrowth. Haploinsufficiency of the nuclear receptor SET domain-containing protein 1 (NSD1) gene located on 5q35 has been implicated as the cause of Sotos syndrome. This study was performed to investigate the mutation spectrum of NSD1 abnormalities and meaningful genotype-phenotype correlations in Korean patients with Sotos syndrome. Eighteen unrelated Korean patients with Sotos syndrome were enrolled for clinical and molecular analyses. Cytogenetic studies were performed to confirm 5q35 microdeletion, and NSD1 sequencing analysis was performed to identify intragenic mutations. NSD1 abnormalities were identified in 15 (83%) patients. Among them, eight patients (53%) had 5q35 microdeletions and the other seven patients (47%) had seven different NSD1 intragenic mutations including four novel mutations. The mutation spectrum of Korean patients with Sotos syndrome was similar to that of previous studies for Japanese patients. Height was significantly shorter and age of walking alone was significantly older in the microdeletion group compared with those in the intragenic mutation group. No significant differences were observed for other clinical characteristics between the microdeletion and intragenic mutation groups. Further studies with a larger number of patients will be necessary to draw conclusive genotype-phenotype correlations.


Assuntos
Deleção Cromossômica , Cromossomos Humanos Par 5 , Peptídeos e Proteínas de Sinalização Intracelular/genética , Mutação , Proteínas Nucleares/genética , Síndrome de Sotos/genética , Síndrome de Sotos/patologia , Adolescente , Criança , Pré-Escolar , Feminino , Histona Metiltransferases , Histona-Lisina N-Metiltransferase , Humanos , Hibridização in Situ Fluorescente , Masculino , República da Coreia
19.
Mamm Genome ; 23(11-12): 749-57, 2012 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-22926222

RESUMO

Haploinsufficiency of the human 5q35 region spanning the NSD1 gene results in a rare genomic disorder known as Sotos syndrome (Sotos), with patients displaying a variety of clinical features, including pre- and postnatal overgrowth, intellectual disability, and urinary/renal abnormalities. We used chromosome engineering to generate a segmental monosomy, i.e., mice carrying a heterozygous 1.5-Mb deletion of 36 genes on mouse chromosome 13 (4732471D19Rik-B4galt7), syntenic with 5q35.2-q35.3 in humans (Df(13)Ms2Dja ( +/- ) mice). Surprisingly Df(13)Ms2Dja ( +/- ) mice were significantly smaller for their gestational age and also showed decreased postnatal growth, in contrast to Sotos patients. Df(13)Ms2Dja ( +/- ) mice did, however, display deficits in long-term memory retention and dilation of the pelvicalyceal system, which in part may model the learning difficulties and renal abnormalities observed in Sotos patients. Thus, haploinsufficiency of genes within the mouse 4732471D19Rik-B4galt7 deletion interval play important roles in growth, memory retention, and the development of the renal pelvicalyceal system.


Assuntos
Deleção Cromossômica , Cromossomos Humanos Par 5/genética , Modelos Animais de Doenças , Crescimento e Desenvolvimento/genética , Transtornos da Memória/genética , Síndrome de Sotos/genética , Absorciometria de Fóton , Animais , Southern Blotting , Pesos e Medidas Corporais , Hibridização Genômica Comparativa , Primers do DNA/genética , Marcação de Genes/métodos , Haploinsuficiência/genética , Técnicas Histológicas , Humanos , Hibridização in Situ Fluorescente , Rim/anormalidades , Camundongos , Síndrome de Sotos/patologia
20.
J Indian Soc Pedod Prev Dent ; 29(6 Suppl 2): S48-51, 2011 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-22169837

RESUMO

Sotos syndrome is a well-defined childhood overgrowth syndrome characterized by pre- and postnatal overgrowth, developmental delay, advanced bone age, and a typical facial gestalt including macrodolichocephaly with frontal bossing, frontoparietal sparseness of hair, apparent hypertelorism, downslanting palpebral fissures, and facial flushing. This report presents a case of Sotos syndrome in a 5½-year-old child.


Assuntos
Assistência Odontológica para Doentes Crônicos , Cárie Dentária/etiologia , Síndrome de Sotos/patologia , Pré-Escolar , Cárie Dentária/terapia , Diagnóstico Diferencial , Feminino , Humanos , Síndrome de Sotos/complicações
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