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1.
BMC Pregnancy Childbirth ; 24(1): 338, 2024 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-38702634

RESUMO

OBJECTIVE: This study aims to perform a prenatal genetic diagnosis of a high-risk fetus with trisomy 7 identified by noninvasive prenatal testing (NIPT) and to evaluate the efficacy of different genetic testing techniques for prenatal diagnosis of trisomy mosaicism. METHODS: For prenatal diagnosis of a pregnant woman with a high risk of trisomy 7 suggested by NIPT, karyotyping and chromosomal microarray analysis (CMA) were performed on an amniotic fluid sample. Low-depth whole-genome copy number variation sequencing (CNV-seq) and fluorescence in situ hybridization (FISH) were used to clarify the results further. In addition, methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA) was performed to analyze the possibility of uniparental disomy(UPD). RESULTS: Amniotic fluid karyotype analysis revealed a 46, XX result. Approximately 20% mosaic trisomy 7 was detected according to the CMA result. About 16% and 4% of mosaicism was detected by CNV-seq and FISH, respectively. MS-MLPA showed no methylation abnormalities. The fetal ultrasound did not show any detectable abnormalities except for mild intrauterine growth retardation seen at 39 weeks of gestation. After receiving genetic counseling, the expectant mother decided to continue the pregnancy, and follow-up within three months of delivery was normal. CONCLUSION: In high-risk NIPT diagnosis, a combination of cytogenetic and molecular genetic techniques proves fruitful in detecting low-level mosaicism. Furthermore, the exclusion of UPD on chromosome 7 remains crucial when NIPT indicates a positive prenatal diagnosis of trisomy 7.


Assuntos
Cromossomos Humanos Par 7 , Variações do Número de Cópias de DNA , Hibridização in Situ Fluorescente , Cariotipagem , Mosaicismo , Trissomia , Dissomia Uniparental , Humanos , Feminino , Mosaicismo/embriologia , Gravidez , Hibridização in Situ Fluorescente/métodos , Cromossomos Humanos Par 7/genética , Trissomia/diagnóstico , Trissomia/genética , Cariotipagem/métodos , Adulto , Dissomia Uniparental/diagnóstico , Dissomia Uniparental/genética , Diagnóstico Pré-Natal/métodos , Análise em Microsséries/métodos , Teste Pré-Natal não Invasivo/métodos , Reação em Cadeia da Polimerase Multiplex/métodos , Líquido Amniótico
2.
J Neuropathol Exp Neurol ; 83(5): 338-344, 2024 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-38605523

RESUMO

EGFR amplification in gliomas is commonly defined by an EGFR/CEP7 ratio of ≥2. In testing performed at a major reference laboratory, a small subset of patients had ≥5 copies of both EGFR and CEP7 yet were not amplified by the EGFR/CEP7 ratio and were designated high polysomy cases. To determine whether these tumors are more closely related to traditionally defined EGFR-amplified or nonamplified gliomas, a retrospective search identified 22 out of 1143 (1.9%) gliomas with an average of ≥5 copies/cell of EGFR and CEP7 with an EGFR/CEP7 ratio of <2 displaying high polysomy. Of these cases, 4 had insufficient clinicopathologic data to include in additional analysis, 15 were glioblastomas, 2 were IDH-mutant astrocytomas, and 1 was a high-grade glial neoplasm, NOS. Next-generation sequencing available on 3 cases demonstrated one with a TERT promoter mutation, TP53 mutations in all cases, and no EGFR mutations or amplifications, which most closely matched the nonamplified cases. The median overall survival times were 42.86, 66.07, and 41.14 weeks for amplified, highly polysomic, and nonamplified, respectively, and were not significantly different (p = 0.3410). High chromosome 7 polysomic gliomas are rare but our data suggest that they may be biologically similar to nonamplified gliomas.


Assuntos
Neoplasias Encefálicas , Amplificação de Genes , Glioblastoma , Glioma , Humanos , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patologia , Aberrações Cromossômicas , Receptores ErbB/genética , Glioblastoma/genética , Glioblastoma/patologia , Glioma/genética , Glioma/patologia , Hibridização in Situ Fluorescente , Isocitrato Desidrogenase/genética , Mutação/genética , Estudos Retrospectivos , Cromossomos Humanos Par 7/genética
3.
Leukemia ; 38(5): 1182-1186, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38443608

RESUMO

Monosomy 7 and del(7q) are among the most common and poorly understood genetic alterations in myelodysplastic neoplasms and acute myeloid leukemia. Chromosome band 7q22 is a minimally deleted segment in myeloid malignancies with a del(7q). However, the rarity of "second hit" mutations supports the idea that del(7q22) represents a contiguous gene syndrome. We generated mice harboring a 1.5 Mb germline deletion of chromosome band 5G2 syntenic to human 7q22 that removes Cux1 and 27 additional genes. Hematopoiesis is perturbed in 5G2+/del mice but they do not spontaneously develop hematologic disease. Whereas alkylator exposure modestly accelerated tumor development, the 5G2 deletion did not cooperate with KrasG12D, NrasG12D, or the MOL4070LTR retrovirus in leukemogenesis. 5G2+/del mice are a novel platform for interrogating the role of hemopoietic stem cell attrition/stress, cooperating mutations, genotoxins, and inflammation in myeloid malignancies characterized by monosomy 7/del(7q).


Assuntos
Deleção Cromossômica , Modelos Animais de Doenças , Animais , Camundongos , Cromossomos Humanos Par 7/genética , Humanos , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/patologia , Síndromes Mielodisplásicas/genética , Síndromes Mielodisplásicas/patologia , Camundongos Endogâmicos C57BL
4.
Haematologica ; 109(2): 422-430, 2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-37584291

RESUMO

Monosomy 7 is the most common cytogenetic abnormality in pediatric myelodysplastic syndrome (MDS) and associated with a high risk of disease progression. However, in young children, spontaneous loss of monosomy 7 with concomitant hematologic recovery has been described, especially in the presence of germline mutations in SAMD9 and SAMD9L genes. Here, we report on our experience of close surveillance instead of upfront hematopoietic stem cell transplantation (HSCT) in seven patients diagnosed with SAMD9L syndrome and monosomy 7 at a median age of 0.6 years (range, 0.4-2.9). Within 14 months from diagnosis, three children experienced spontaneous hematological remission accompanied by a decrease in monosomy 7 clone size. Subclones with somatic SAMD9L mutations in cis were identified in five patients, three of whom attained hematological remission. Two patients acquired RUNX1 and EZH2 mutations during the observation period, of whom one progressed to myelodysplastic syndrome with excess of blasts (MDS-EB). Four patients underwent allogeneic HSCT at a median time of 26 months (range, 14-40) from diagnosis for MDSEB, necrotizing granulomatous lymphadenitis, persistent monosomy 7, and severe neutropenia. At last follow-up, six patients were alive, while one passed away due to transplant-related causes. These data confirm previous observations that monosomy 7 can be transient in young children with SAMD9L syndrome. However, they also indicate that delaying HSCT poses a substantial risk of severe infection and disease progression. Finally, surveillance of patients with SAMD9L syndrome and monosomy 7 is critical to define the evolving genetic landscape and to determine the appropriate timing of HSCT (clinicaltrials gov. Identifier: NCT00662090).


Assuntos
Deleção Cromossômica , Síndromes Mielodisplásicas , Humanos , Criança , Pré-Escolar , Lactente , Remissão Espontânea , Síndromes Mielodisplásicas/diagnóstico , Síndromes Mielodisplásicas/genética , Síndromes Mielodisplásicas/terapia , Progressão da Doença , Fatores de Transcrição/genética , Monossomia , Cromossomos Humanos Par 7/genética , Peptídeos e Proteínas de Sinalização Intracelular/genética
5.
Rev. Hosp. Ital. B. Aires (2004) ; 43(3): 143-146, sept. 2023. ilus, tab
Artigo em Espanhol | LILACS, UNISALUD, BINACIS | ID: biblio-1517927

RESUMO

Se presenta un niño de 6 años con antecedente de retraso del lenguaje que llevó a sus padres a realizar múltiples consultas. En un primer momento, su cuadro fue interpretado como parte de un retraso global del desarrollo. Posteriormente, el paciente presentó convulsiones y episodios de descompensación metabólica, comenzando desde entonces su seguimiento por los Servicios de neurología, genética y metabolismo. Finalmente, tras varios estudios complementarios, por medio de un exoma trío se arribó al diagnóstico de síndrome de microduplicación del cromosoma 7q11.23, lo que justifica tanto el retraso global de desarrollo del paciente como su clínica neurológica. (AU)


A six-year-old boy presents with a history of language delay that led his parents to make multiple consultations. At first, we interpreted his condition as part of a global developmental delay. Subsequently, the patient presented seizures and episodes of metabolic decompensation, and since then, he had to be followed up by neurology, genetics, and metabolism services. Finally, after several complementary studies, following a trio exome analysis, we diagnosed chromosome 7q11.23 microduplication syndrome, which explains his global developmental delay and neurological symptoms. (AU)


Assuntos
Humanos , Masculino , Criança , Cromossomos Humanos Par 7/genética , Deficiências do Desenvolvimento/genética , Síndrome de Williams/genética , Duplicação Cromossômica , Transtornos do Desenvolvimento da Linguagem/genética , Deficiência Intelectual/genética , Deficiências do Desenvolvimento/diagnóstico , Deficiências do Desenvolvimento/metabolismo , Testes Genéticos , Síndrome de Williams/diagnóstico , Síndrome de Williams/metabolismo , Transtornos do Desenvolvimento da Linguagem/diagnóstico , Deficiência Intelectual/diagnóstico , Deficiência Intelectual/metabolismo
6.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 40(7): 828-832, 2023 Jul 10.
Artigo em Chinês | MEDLINE | ID: mdl-37368384

RESUMO

OBJECTIVE: To explore the clinical and genetic characteristics of two children with Williams-Beuren syndrome (WBS). METHODS: Two children who had presented at the Department of Pediatrics, General Hospital of Ningxia Medical University respectively on January 26 and March 18, 2021 were selected as the study subjects. Clinical data and results of genetic testing of the two patients were analyzed. RESULTS: Both children had featured developmental delay, characteristic facies and cardiovascular malformation. Child 1 also had subclinical hypothyroidism, whilst child 2 had occurrence of epilepsy. Genetic testing revealed that child 1 has harbored a 1.54 Mb deletion in the 7q11.23 region, whilst child 2 has a 1.53 Mb deletion in the same region, in addition with a c.158G>A variant of the ATP1A1 gene and a c.12181A>G variant of the KMT2C gene. Based on the guidelines from the American College of Medical Genetics and Genomics, the c.158G>A and c.12181A>G variants were rated as variants of unknown significance (PM1+PM2_Supporting+PP2+PP3;PM2_Supporting). CONCLUSION: Both children had characteristic features of WBS, for which deletions of the 7q11.23 region may be accountable. For children manifesting developmental delay, facial dysmorphism and cardiovascular malformations, the diagnosis of WBS should be suspected, and genetic testing should be recommended to confirm the diagnosis.


Assuntos
Epilepsia , Síndrome de Williams , Criança , Humanos , Síndrome de Williams/genética , Síndrome de Williams/diagnóstico , Testes Genéticos , Fácies , Epilepsia/genética , Cromossomos Humanos Par 7/genética , Deleção Cromossômica
7.
Am J Med Genet A ; 191(7): 1849-1857, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37081310

RESUMO

Partial deletions at chromosome 7q11.23 are causative for the autosomal-dominant Williams-Beuren syndrome (WBS), whereas the partial duplication of this region leads to the 7q11.23 duplication syndrome. Both syndromes are highly penetrant and occur with a frequency of 1:7500-10,000 (WBS) and 1:13,000-20,000 (7q11.23 duplication syndrome). They are associated with multiple organ defects, intellectual disability, and typical facial dysmorphisms showing broad phenotypic variability. The 7q11.23 region is susceptible to chromosomal rearrangements due to flanking segmental duplications and regions of long repetitive DNA segments. Here, we report on a family with two children affected by WBS and clinically unaffected parents. Interestingly, metaphase fluorescence in situ hybridization (FISH) revealed a deletion on 7q11.23 in the father. Intensive genetic testing, using interphase FISH, whole genome sequencing and optical genome mapping led to the confirmation of a 1.5 Mb deletion at one 7q11.23 allele and the identification of a reciprocal 1.8 Mb duplication at the other allele. This finding is highly important regarding genetic counseling in this family. The father is a silent carrier for two syndromic disorders, thus his risk to transmit a disease-causing allele is 100%. To the best of our knowledge we, here, report on the first case in which the phenotype of a microdeletion/microduplication syndrome was compensated by its reciprocal counterpart.


Assuntos
Síndrome de Williams , Humanos , Hibridização in Situ Fluorescente , Síndrome de Williams/genética , Testes Genéticos , Fenótipo , Aberrações Cromossômicas , Cromossomos Humanos Par 7/genética , Deleção Cromossômica
8.
Int J Hematol ; 118(3): 406-410, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37022561

RESUMO

Acute myeloid leukemia (AML) with chromosome 7 abnormalities has a dismal prognosis due to a poor complete remission (CR) rate after induction chemotherapy. Although various salvage therapies for refractory AML have been developed for adults, few salvage therapies are available for children. Here, we report the cases of three patients with refractory AML with chromosome 7 abnormalities (Patient 1, with inv(3)(q21;3q26.2) and monosomy 7; Patient 2, with der(7)t(1;7)(?;q22); patient 3, with monosomy 7) who were successfully treated with L-asparaginase (L-ASP) as salvage therapy. All three patients achieved CR several weeks after L-ASP treatment, and two patients successfully underwent hematopoietic stem cell transplantation (HSCT). Patient 2 relapsed after the second HSCT in the form of an intracranial lesion, but achieved and sustained CR for 3 years with weekly L-ASP maintenance therapy. Immunohistochemical staining for asparagine synthetase (ASNS), whose gene is located at 7q21.3, was performed for each patient. The result was negative in all patients, which suggests that haploid 7q21.3 and other chromosome 7 abnormalities leading to haploinsufficiency of ASNS contribute to a high susceptibility to L-ASP. In conclusion, L-ASP is a promising salvage therapy for refractory AML with chromosome 7 abnormalities, which are associated with ASNS haploinsufficiency.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Leucemia Mieloide Aguda , Adulto , Criança , Humanos , Asparaginase , Terapia de Salvação , Cromossomos Humanos Par 7/genética , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia Mieloide Aguda/genética , Aberrações Cromossômicas , Prognóstico , Indução de Remissão , Estudos Retrospectivos
9.
J Pediatr Hematol Oncol ; 45(1): e1-e3, 2023 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-35973025

RESUMO

Complete or partial loss of chromosome 7 is a common and well-known cytogenetic abnormality associated with preleukemic myelodysplasia and myeloid leukemia but not with autoimmune myelofibrosis. Detection of this molecular change represents poor prognosis. When malignant transformation occurs, the condition tends to be chemotherapy-resistant requiring haematopoietic stem cell transplantation (HSCT) to obtain a cure. Disappearance after immunosuppressive therapy has been documented in children with hematological disorders but not in association with cyclophosphamide and systemic lupus erythematous.We present the interesting case of a 12-year-old male with monosomy 7, systemic lupus erythematous, and lupus nephritis with the resolution of the monosomy 7 and autoimmune myelofibrosis after treatment with cyclophosphamide, along with a review of the literature.


Assuntos
Nefrite Lúpica , Mielofibrose Primária , Masculino , Criança , Humanos , Nefrite Lúpica/complicações , Nefrite Lúpica/genética , Mielofibrose Primária/complicações , Mielofibrose Primária/genética , Mielofibrose Primária/terapia , Cromossomos Humanos Par 7/genética , Ciclofosfamida , Imunossupressores
10.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-981830

RESUMO

OBJECTIVE@#To explore the clinical and genetic characteristics of two children with Williams-Beuren syndrome (WBS).@*METHODS@#Two children who had presented at the Department of Pediatrics, General Hospital of Ningxia Medical University respectively on January 26 and March 18, 2021 were selected as the study subjects. Clinical data and results of genetic testing of the two patients were analyzed.@*RESULTS@#Both children had featured developmental delay, characteristic facies and cardiovascular malformation. Child 1 also had subclinical hypothyroidism, whilst child 2 had occurrence of epilepsy. Genetic testing revealed that child 1 has harbored a 1.54 Mb deletion in the 7q11.23 region, whilst child 2 has a 1.53 Mb deletion in the same region, in addition with a c.158G>A variant of the ATP1A1 gene and a c.12181A>G variant of the KMT2C gene. Based on the guidelines from the American College of Medical Genetics and Genomics, the c.158G>A and c.12181A>G variants were rated as variants of unknown significance (PM1+PM2_Supporting+PP2+PP3;PM2_Supporting).@*CONCLUSION@#Both children had characteristic features of WBS, for which deletions of the 7q11.23 region may be accountable. For children manifesting developmental delay, facial dysmorphism and cardiovascular malformations, the diagnosis of WBS should be suspected, and genetic testing should be recommended to confirm the diagnosis.


Assuntos
Criança , Humanos , Síndrome de Williams/diagnóstico , Testes Genéticos , Fácies , Epilepsia/genética , Cromossomos Humanos Par 7/genética , Deleção Cromossômica
11.
Leuk Lymphoma ; 63(13): 3105-3116, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36089905

RESUMO

Deletions in chromosome 7 (del(7)) or its long arm (del(7q)) constitute the most common adverse cytogenetic events in acute myeloid leukemia (AML). We retrospectively analyzed 243 treatment-naive patients with AML and del(7) (168/243; 69%) or del(7q) (75/243; 31%) who did not receive any myeloid-directed therapy prior to AML diagnosis. This is the largest comprehensive clinical and molecular analysis of AML patients with del(7) and del(7q). Our results show that relapse-free survival was significantly longer for AML patients with del(7q) compared to del(7), but the overall survival and remission duration were similar. TP53 mutations and del5/5q were the most frequent co-occurring mutations and cytogenetic abnormalities, and conferred worse outcomes in del(7) and del(7q) patients. Venetoclax-based treatments were associated with worse outcomes in TP53 mutated AML patients with del(7) or del(7q), as well as del(7) with TP53 wildtype status, requiring further investigation.


Assuntos
Cromossomos Humanos Par 7 , Leucemia Mieloide Aguda , Humanos , Cromossomos Humanos Par 7/genética , Estudos Retrospectivos , Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia Mieloide Aguda/genética , Aberrações Cromossômicas , Deleção Cromossômica , Proteína Supressora de Tumor p53/genética
12.
Am J Med Genet A ; 188(8): 2421-2428, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35593535

RESUMO

Maternal uniparental disomy of human chromosome 7 [upd(7)mat] is well-characterized as a cause of the growth disorder Silver-Russell syndrome (SRS). However, the causative gene is not currently known. There is growing evidence that molecular changes at the imprinted MEST region in 7q32.2 are associated with a phenotype evocative of SRS. This report details a patient with a SRS-like phenotype and a paternally inherited microdeletion of 79 kilobases (35-fold smaller than the previously reported smallest deletion) in the 7q32.2 region. This microdeletion encompasses only five genes, including MEST, which corroborates the hypothesis that MEST plays a central role in the 7q32.2 microdeletion growth disorder, as well as further implicating MEST in upd(7)mat SRS itself.


Assuntos
Síndrome de Silver-Russell , Cromossomos Humanos Par 7/genética , Impressão Genômica , Transtornos do Crescimento/genética , Humanos , Herança Paterna , Fenótipo , Síndrome de Silver-Russell/diagnóstico , Síndrome de Silver-Russell/genética , Dissomia Uniparental/genética
14.
PLoS One ; 17(1): e0250799, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35020748

RESUMO

Carotid plaque is a subclinical measure of atherosclerosis. We have previously shown measures of carotid plaque to be heritable in a sample of 100 Dominican families and found evidence for linkage and association of common variants (CVs) on 7q36, 11p15, 14q32 and 15q23 with plaque presence. Our current study aimed to refine these regions further and identify rare variants (RVs) influencing plaque presence. Therefore, we performed targeted sequencing of the one LOD unit down region on 7q36, 11p15, 14q32 and 15q23 in 12 Dominican families with evidence for linkage to plaque presence. Gene-based RV analyses were performed using the Sequence Association Test for familial data (F-SKAT) under two filtering algorithms; 1. all exonic RVs and 2. non-synonymous RVs. Replication analyses were performed using a sample of 22 Dominican families and 556 unrelated Dominicans with Exome Array data. To identify additional non-synonymous RVs influencing plaque, we looked for co-segregation of RVs with plaque in each of the sequenced families. Our most strongly associated gene with evidence for replication was AMPD3 which showed suggestive association with plaque presence in the sequenced families (exonic RV p = 0.003, nonsynonymous RV p = 0.005) and replication families (exonic RV p = 0.04, nonsynonymous RV p = 0.02). Examination of the sequenced family pedigrees revealed two missense variants on chromosome 11 which co-segregated with plaque presence in one of our families; rs61751342 (located in DENND2B), and rs61760882 (located in RNF141). The rs61751342 missense variant is an eQTL for SCUBE2 in the atrial appendage. Notably, SCUBE2 encodes a protein which interacts with vascular endothelial growth factor (VEGF) receptor 2 to regulate VEGF-induced angiogenesis, thus providing biologic plausibility for this gene in atherosclerosis. In conclusion, using targeted sequencing of previously-identified linkage regions, we have identified suggestive evidence for the role of RVs in carotid plaque pathogenesis.


Assuntos
Ligação Genética , Placa Aterosclerótica/genética , AMP Desaminase/genética , Proteínas Adaptadoras de Transdução de Sinal/genética , Adulto , Idoso , Proteínas de Ligação ao Cálcio/genética , Cromossomos Humanos Par 11/genética , Cromossomos Humanos Par 14/genética , Cromossomos Humanos Par 15/genética , Cromossomos Humanos Par 7/genética , Proteínas de Ligação a DNA/genética , República Dominicana , Genótipo , Humanos , Pessoa de Meia-Idade , Linhagem , Placa Aterosclerótica/patologia , Polimorfismo Genético , Locos de Características Quantitativas , Fatores de Transcrição/genética , Proteínas Supressoras de Tumor/genética , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/genética
15.
Curr Opin Hematol ; 29(2): 92-102, 2022 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-35084368

RESUMO

PURPOSE OF REVIEW: Loss of chromosome 7 has long been associated with adverse-risk myeloid malignancy. In the last decade, CUX1 has been identified as a critical tumor suppressor gene (TSG) located within a commonly deleted segment of chromosome arm 7q. Additional genes encoded on 7q have also been identified as bona fide myeloid tumor suppressors, further implicating chromosome 7 deletions in disease pathogenesis. This review will discuss the clinical implications of del(7q) and CUX1 mutations, both in disease and clonal hematopoiesis, and synthesize recent literature on CUX1 and other chromosome 7 TSGs. RECENT FINDINGS: Two major studies, including a new mouse model, have been published that support a role for CUX1 inactivation in the development of myeloid neoplasms. Additional recent studies describe the cellular and hematopoietic effects from loss of the 7q genes LUC7L2 and KMT2C/MLL3, and the implications of chromosome 7 deletions in clonal hematopoiesis. SUMMARY: Mounting evidence supports CUX1 as being a key chromosome 7 TSG. As 7q encodes additional myeloid regulators and tumor suppressors, improved models of chromosome loss are needed to interrogate combinatorial loss of these critical 7q genes.


Assuntos
Transtornos Mieloproliferativos , Neoplasias , Animais , Deleção Cromossômica , Cromossomos Humanos Par 7/genética , Hematopoiese Clonal , Proteínas de Homeodomínio/genética , Humanos , Camundongos , Transtornos Mieloproliferativos/genética , Neoplasias/genética , Proteínas Repressoras/genética , Fatores de Transcrição/genética
17.
J Matern Fetal Neonatal Med ; 35(22): 4268-4272, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33213225

RESUMO

Clinical cases of chromosome 7 long-arm end deletion are rare. Generally, 7q terminal deletion syndrome results in complex clinical phenotypes, such as microcephaly, growth and development retardation, holoprosencephaly, and sacral hypoplasia. Herein, we report the genetic and clinical features of a fetus with multiple malformations observed by prenatal ultrasound. The results showed that there was a large fragment deletion of approximately 27.7 Mb in 7q32.3-qter. The induced fetus showed facial abnormalities of cleft lip and palate, and some organ structural abnormalities (such as diaphragmatic hernia and polycystic renal dysplasia) were observed by autopsy and pathology. To provide more reliable information for disease diagnosis and genetic counseling, we reviewed and analyzed the reported cases of isolated 7q terminal syndrome.


Assuntos
Anormalidades Múltiplas , Fenda Labial , Fissura Palatina , Anormalidades Múltiplas/diagnóstico por imagem , Anormalidades Múltiplas/genética , Aberrações Cromossômicas , Deleção Cromossômica , Transtornos Cromossômicos , Cromossomos Humanos Par 7/genética , Fissura Palatina/genética , Feminino , Humanos , Leucemia Mieloide Aguda , Síndromes Mielodisplásicas , Gravidez , Diagnóstico Pré-Natal , Ultrassonografia Pré-Natal
18.
J Pediatr Hematol Oncol ; 44(1): e109-e113, 2022 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-33625084

RESUMO

Therapy-related myeloid neoplasm (t-MN) in the pediatric population is not well characterized. We studied 12 pediatric patients diagnosed with t-MN in our institution since 2006. The median age at the t-MN diagnoses was 14.8 years (range, 9 to 20 y). The primary malignancies included 9 solid tumors and 3 hematopoietic malignancies. Rhabdomyosarcoma (n=4) was the most common primary malignancy. Five of the 9 patients with solid tumors and all 3 patients with hematopoietic malignancies had primary neoplasms involving bone marrow. The median latency period was 5.2 years (range, 1.8 to 13.8 y). Thrombocytopenia was present in all patients at the t-MN diagnoses. Complete or partial monosomy of chromosome 5 or 7 were the 2 most common cytogenetic abnormalities. A quarter of patients demonstrated a genetic predisposition to t-MN: 1 with Li-Fraumeni syndrome with a germline TP53 R248Q mutation, 1 with Noonan syndrome with a somatic mutation (PTPN11 S502T), and 1 with a constitutive chromosomal translocation [t(X;9)(p22;q34)] and a germline TP53 L130V mutation. Outcomes remain poor. Two patients survived 3 and 5.1 years after hematopoietic stem cell transplantation.


Assuntos
Cromossomos Humanos Par 5/genética , Predisposição Genética para Doença , Neoplasias Hematológicas , Transplante de Células-Tronco Hematopoéticas , Síndrome de Li-Fraumeni , Transtornos Mieloproliferativos , Segunda Neoplasia Primária , Síndrome de Noonan , Rabdomiossarcoma , Adolescente , Adulto , Aloenxertos , Criança , Pré-Escolar , Deleção Cromossômica , Cromossomos Humanos Par 7/genética , Feminino , Neoplasias Hematológicas/epidemiologia , Neoplasias Hematológicas/genética , Humanos , Lactente , Síndrome de Li-Fraumeni/epidemiologia , Síndrome de Li-Fraumeni/genética , Síndrome de Li-Fraumeni/terapia , Masculino , Transtornos Mieloproliferativos/epidemiologia , Transtornos Mieloproliferativos/genética , Segunda Neoplasia Primária/epidemiologia , Segunda Neoplasia Primária/genética , Síndrome de Noonan/epidemiologia , Síndrome de Noonan/genética , Síndrome de Noonan/terapia , Rabdomiossarcoma/epidemiologia , Rabdomiossarcoma/genética , Rabdomiossarcoma/terapia , Adulto Jovem
19.
Genes (Basel) ; 12(11)2021 10 23.
Artigo em Inglês | MEDLINE | ID: mdl-34828280

RESUMO

Greig cephalopolysyndactyly syndrome (GCPS) is a rare genetic disorder (about 200 cases reported), characterized by macrocephaly, hypertelorism, and polysyndactyly. Most of the reported GCPS cases are the results of heterozygous loss of function mutations affecting the GLI3 gene (OMIM# 175700), while a small proportion of cases arise from large deletions on chromosome 7p14 encompassing the GLI3 gene. To our knowledge, only 6 patients have been reported to have a deletion with an exact size (given by genomic coordinates) and a gene content larger than 1 Mb involving the GLI3 gene. This report presents a patient with Greig cephalopolysyndactyly contiguous gene syndrome (GCP-CGS) diagnosed with a large, 18 Mb deletion on chromosome 7p14.2-p11.2. Similar cases are reviewed in the literature for a more accurate comparison between genotype and phenotype.


Assuntos
Acrocefalossindactilia/genética , Deleção Cromossômica , Cromossomos Humanos Par 7/genética , Proteínas do Tecido Nervoso/genética , Proteína Gli3 com Dedos de Zinco/genética , Pré-Escolar , Hibridização Genômica Comparativa , Humanos , Cariótipo , Masculino
20.
Genes (Basel) ; 12(10)2021 10 12.
Artigo em Inglês | MEDLINE | ID: mdl-34680999

RESUMO

Autism spectrum disorders (ASD) are a group of complex neurodevelopmental disorders, characterized by a deficit in social interaction and communication. Many genetic variants are associated with ASD, including duplication of 7q11.23 encompassing 26-28 genes. Symmetrically, the hemizygous deletion of 7q11.23 causes Williams-Beuren syndrome (WBS), a multisystem disorder characterized by "hyper-sociability" and communication skills. Interestingly, deletion of four non-exonic mobile elements (MEs) in the "canine WBS locus" were associated with the behavioral divergence between the wolf and the dog and dog sociability and domestication. We hypothesized that indel of these MEs could be involved in ASD, associated with its different phenotypes and useful as biomarkers for patient stratification and therapeutic design. Since these MEs are non-exonic they have never been discovered before. We searched the corresponding MEs and loci in humans by comparative genomics. Interestingly, they mapped on different but ASD related genes. The loci in individuals with phenotypically different autism and neurotypical controls were amplified by PCR. A sub-set of each amplicon was sequenced by Sanger. No variant resulted associated with ASD and neither specific phenotypes were found but novel small-scale insertions and SNPs were discovered. Since MEs are hyper-methylated and epigenetically modulate gene expression, further investigation in ASD is necessary.


Assuntos
Transtorno do Espectro Autista/genética , Deleção Cromossômica , Sequências Repetitivas Dispersas/genética , Síndrome de Williams/genética , Animais , Transtorno do Espectro Autista/fisiopatologia , Comportamento Animal/fisiologia , Cromossomos Humanos Par 7/genética , Hibridização Genômica Comparativa , Cães , Domesticação , Genômica , Humanos , Fenótipo , Habilidades Sociais , Síndrome de Williams/fisiopatologia , Lobos/fisiologia
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