RESUMO
OBJECTIVE: We studied our collective open-label, compassionate use experience in using cannabidiol (CBD) to treat epilepsy in patients with CDKL5 deficiency disorder and Aicardi, Doose, and Dup15q syndromes. METHODS: We included patients aged 1-30â¯years with severe childhood-onset epilepsy who received CBD for ≥10â¯weeks as part of multiple investigator-initiated expanded access or state access programs for a compassionate prospective interventional study: CDKL5 deficiency disorder (nâ¯=â¯20), Aicardi syndrome (nâ¯=â¯19), Dup15q syndrome (nâ¯=â¯8), and Doose syndrome (nâ¯=â¯8). These patients were treated at 11 institutions from January 2014 to December 2016. RESULTS: The percent change in median convulsive seizure frequency for all patients taking CBD in the efficacy group decreased from baseline [nâ¯=â¯46] to week 12 (51.4% [nâ¯=â¯35], interquartile range (IQR): 9-85%) and week 48 (59.1% [nâ¯=â¯27], IQR: 14-86%). There was a significant difference between the percent changes in monthly convulsive seizure frequency during baseline and week 12, χ2(2)â¯=â¯22.9, pâ¯=â¯0.00001, with no difference in seizure percent change between weeks 12 and 48. Of the 55 patients in the safety group, 15 (27%) withdrew from extended observation by week 144: 4 due to adverse effects, 9 due to lack of efficacy, 1 withdrew consent, and 1 was lost to follow-up. SIGNIFICANCE: This open-label drug trial provides class III evidence for the long-term safety and efficacy of CBD administration in patients with treatment-resistant epilepsy (TRE) associated with CDKL5 deficiency disorder and Aicardi, Dup15q, and Doose syndromes. Adjuvant therapy with CBD showed similar safety and efficacy for these four syndromes as reported in a diverse population of TRE etiologies. This study extended analysis of the prior report from 12â¯weeks to 48â¯weeks of efficacy data and suggested that placebo-controlled randomized trials should be conducted to formally assess the safety and efficacy of CBD in these epileptic encephalopathies.
Assuntos
Síndrome de Aicardi/tratamento farmacológico , Anticonvulsivantes/uso terapêutico , Canabidiol/uso terapêutico , Cromossomos Humanos 13-15/genética , Epilepsias Mioclônicas/tratamento farmacológico , Síndromes Epilépticas/tratamento farmacológico , Espasmos Infantis/tratamento farmacológico , Adolescente , Adulto , Síndrome de Aicardi/diagnóstico , Anticonvulsivantes/química , Canabidiol/química , Criança , Pré-Escolar , Epilepsias Mioclônicas/diagnóstico , Síndromes Epilépticas/diagnóstico , Feminino , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Proteínas Serina-Treonina Quinases/deficiência , Espasmos Infantis/diagnóstico , Trissomia/genética , Adulto JovemRESUMO
OBJECTIVE: To assess the risk of male infertility in the offspring conceived through assisted reproductive technology (ART) byin vitroinductionof the differentiation of embryonic stem cells (ESCs) derived from the embryos of the couples with male asthenozoospermia and Robertsonian translocation (RT) into germ cells. METHODS: We established a CCRM16ESC line with the karyotype of 46, XY, +14, rob(13; 14) (q10; q10) from the embryo donated by a patientwithasthenozoospermiaand RT and his wife by isolation of the inner cell mass of blastula, culturing, passaging, and amplification,followed by in vitro induction and differentiationof the ESCs into germ cells with ratinoic acid(RA) at 2 mol/L. Then, we analyzed the process of differentiation and the expressions of its related genes and compared them with those in the normal CCRM23ESCs. RESULTS: CCRM16 showed the typical characteristics of ESCs, expressing the pluripotency makers of NANOG, OCT4, TRA-1-181 and SSEA4, forming embryoid bodies, and differentiating into three germlayer tissues in vitro and in vivo. Intervention with 2 mol/LRAinduced direct differentiation of the ESCs into germ cells. The expressions of the primordial germ cell marker geneDAZLand the meiosis marker geneSCP3were markedly decreased in the CCRM16 as compared with those in the normal CCRM23 ESCs. CONCLUSIONS: The CCRM16ESC linewith the karyotype of46, XY, +14, rob(13; 14) (q10; q10) has thetypical characteristics of ESCs but an abnormal process of differentiation into germ cells in the early stage. In vitroinductionof the differentiation of ESCs into germ cells can be used for assessing the risk of male infertility in the offspring conceived through ART for asthenozoospermia patients.
Assuntos
Cariótipo Anormal , Astenozoospermia/patologia , Massa Celular Interna do Blastocisto , Diferenciação Celular/genética , Cromossomos Humanos 13-15/genética , Células-Tronco Embrionárias/citologia , Células Germinativas/citologia , Infertilidade Masculina/etiologia , Translocação Genética/genética , Animais , Astenozoospermia/genética , Linhagem Celular , Marcadores Genéticos , Humanos , Masculino , Técnicas de Reprodução Assistida , Risco , Antígenos Embrionários Estágio-EspecíficosRESUMO
OBJECTIVES: To report a woman with primary ovarian insufficiency (POI) with reciprocal translocation between chromosomes 5 and 13. METHODS: Chromosomal analysis (G-banding) of a 39-year-old woman with elevated gonadotropin levels and secondary amenorrhea and review of the literature with a special focus on disrupted genes at the reported breakpoints. RESULTS: A reciprocal translocation between the long arms of chromosomes 5 and 13 was identified in the patient (46,XX,t(5;13)(q13;q14)). Investigation of the breakpoints revealed that the 13q14.1 region encompasses FOXO1 (forkhead box 1) gene, which has an important role in granulosa cell function and follicle maturation. CONCLUSIONS: Autosomal translocations are rare in women with POI. We have reported the first case of a de novo reciprocal translocation involving chromosomes 5 and 13 in a POI patient. As one of the breakpoints encompasses the FOXO1 gene, it seems that disruption of this gene can be the cause of POI in this patient. This provides further evidence on the role of autosomal translocations in disrupting POI-associated genes. Therefore, concentrating on the genes at the breakpoints will be helpful to delineate the new biological pathways or genes involved in POI pathogenesis.
Assuntos
Insuficiência Ovariana Primária/genética , Translocação Genética/genética , Adulto , Pontos de Quebra do Cromossomo , Cromossomos Humanos , Cromossomos Humanos 13-15/genética , Cromossomos Humanos 4-5/genética , Feminino , Proteína Forkhead Box O1/genética , Células da Granulosa/fisiologia , Humanos , LinhagemRESUMO
UNLABELLED: The genetic factor remains the most frequent cause of spontaneous abortions. Examination of the fetal tissue from spontaneous miscarriages shows that 75% of them were caused by abnormal karyotype. Other reasons, albeit rare, included submicroscopic genomic rearrangements, monogenic diseases, and polygenic inheritance disorders of the embryo. OBJECTIVE: The aim of the study was to analyze the incidence of chromosomal aberrations in material from the miscarriage. MATERIAL AND METHODS: The study included 47 samples of miscarriage material from 47 women. Fluorescent hybridization in-situ (FISH) was used for genetic examination. RESULTS: Chromosomal abnormalities were diagnosed in 72% of the samples, with trisomy 21 (25.5%), trisomy 16 (17%), and trisomy 18 (12.8%) as the most common. An abnormal number of copies of chromosome 18, 21, 22, indicating the coexistence of trisomy 18, 21, 22, was detected in 1 patient. It was another miscarriage in case of 14 subjects (29.8%). CONCLUSIONS: Chromosomal aberrations were diagnosed in the majority of fetal tissue samples from spontaneous miscarriages. More than one chromosomal aberration in a single embryo is an extremely rare occurrence. Miscarriage due to chromosomal aberrations occurred in the vast majority of women > 35 years of age.
Assuntos
Aborto Espontâneo/genética , Aberrações Cromossômicas/estatística & dados numéricos , Cromossomos Humanos 13-15/genética , Cromossomos Humanos 16-18/genética , Cromossomos Humanos 21-22 e Y/genética , Adulto , Feminino , Humanos , Hibridização in Situ Fluorescente , Idade Materna , Reação em Cadeia da Polimerase , Gravidez , Trissomia/genéticaRESUMO
The learning of cytyogenetic special of cariotip in children with the bronchial asthma maked by course of the investigation of prometahyases chromosomes of limphocytes of the periferic bloods. The quantity of association of acrocentric chromosome was analised. The 82 children in age 6-18 years old with the bronchial asthma and with the different control were learned by results of asthma--test control. In children with the noncontrol bronchial asthma the big frequency of of association of acrocentric chromosome 13-15 (D-D), 21-22 (G-G) n 13-15--21-22 (D-G) were received. In patients with the bronchial asthma the lover mitotic activity by healthy were marked (P(N) < 0.05). With the degree of activity it was decreased.
Assuntos
Asma/genética , Aberrações Cromossômicas , Cromossomos Humanos 13-15/genética , Cromossomos Humanos 21-22 e Y/genética , Linfócitos , Prometáfase/genética , Adolescente , Asma/patologia , Asma/prevenção & controle , Criança , Marcadores Genéticos , Humanos , Cariótipo , Cariotipagem , Linfócitos/patologiaRESUMO
Mutations within the coding regions of the synaptonemal complex gene SYCP3 have previously been reported in women with recurrent miscarriage. The present study found no mutations in any of the coding exons or the intron/exon boundaries among 50 recurrent miscarriage patients with at least one documented trisomic miscarriage, suggesting that mutations in SYCP3 do not contribute significantly to risk for recurrent miscarriage through maternal meiotic nondisjunction.
Assuntos
Aborto Habitual/genética , Proteínas Nucleares/genética , Complexo Sinaptonêmico/genética , Trissomia/genética , Adulto , Proteínas de Ciclo Celular , Cromossomos Humanos 13-15 , Cromossomos Humanos 21-22 e Y , Cromossomos Humanos Par 16/genética , Proteínas de Ligação a DNA , Feminino , Humanos , Mosaicismo , Não Disjunção GenéticaRESUMO
Human cloned antigen-specific T lymphocytes were used to characterize DNA rearrangements using a cDNA probe from the T cell receptor (TCR)-alpha chain gene. Rearranged patterns were detected in some T cell clones, confirming that normal mature T cells are rearranged in TCR-alpha locus. Similarly, rearranged DNA patterns were found in T cell clones from the same panel, using a DNA probe (clone K-40, [1]) isolated from chromosome 14 (14q11), where the TCR-alpha locus has been mapped. These results suggest that this genomic DNA clone is located within the TCR-alpha chain locus.
Assuntos
Cromossomos Humanos 13-15 , Receptores de Antígenos de Linfócitos T/genética , Linfócitos T/fisiologia , Mapeamento Cromossômico , Células Clonais , Clonagem Molecular , Genes , Humanos , Hibridização de Ácido Nucleico , Recombinação GenéticaRESUMO
Our results indicate that there are two major breakpoint cluster regions in chromosome 18 DNA for t(14;18) translocations in follicular lymphomas. The absence of a pFL-1 homologous transcript in a cell line containing a pFL-2-detectable translocation suggests that there may be two different pathogenetic consequences of t(14;18) translocations. One possibility is that, despite the distances between them (greater than 20 kb), breakpoints in the two cluster regions in some way affect transcription of the same gene product, which has not yet been identified. Alternatively, two separate transcriptional units may be involved. The availability of DNA probes for each of the two t(14;18) breakpoint cluster regions will allow further studies regarding the biologic significance of these two genetically distinct classes of t(14;18) translocations.
Assuntos
Cromossomos Humanos 13-15 , Cromossomos Humanos 16-18 , Linfoma/genética , Translocação Genética , Linhagem Celular , Clonagem Molecular , DNA/análise , Enzimas de Restrição do DNA , Humanos , Cariotipagem , Hibridização de Ácido NucleicoRESUMO
The chromosomal location of Ti alpha was determined by hybridization of a radiolabeled cDNA for the alpha chain of human T cell receptor with 12 human X mouse cell hybrid DNAs cleaved with BamHI. Seven hybrids contained human Ti alpha, while the remaining five lacked it. Only human chromosome 14 matched the distribution of human Ti alpha signal across the mapping panel. Hybrids segregating a chromosome 14 translocation were used to demonstrate that Ti alpha is in the region 14pter greater than 14q21. Thus, the alpha and beta chain genes that contribute structural components to the Ti moiety of the human T cell receptor lie on different chromosomes. In humans, the immunoglobulin heavy chain locus and Ti alpha are in different regions of chromosome 14, with Ti alpha more proximal and the immunoglobulin heavy chain locus more distal.
Assuntos
Cromossomos Humanos 13-15 , Receptores de Antígenos de Linfócitos T/genética , Animais , Mapeamento Cromossômico , Ligação Genética , Humanos , Células Híbridas/imunologia , Cadeias Pesadas de Imunoglobulinas/genética , Camundongos , Linfócitos T/imunologiaRESUMO
A cDNA clone encoding the alpha chain of the human T cell receptor was used in connection with somatic cell human-rodent hybrids to determine that the genes coding for the alpha chain are located on chromosome 14 in humans. In situ hybridization confirms this result and further localizes these genes to 14q11-14q12 on this chromosome. Since this region of chromosome has been shown to be nonrandomly involved in a number of T cell neoplasias, this assignment raises a number of interesting questions as to the possible involvement of the T cell receptor alpha chain genes in tumorigenesis.
Assuntos
Cromossomos Humanos 13-15 , Genes , Receptores de Antígenos de Linfócitos T/genética , Linfócitos T/metabolismo , Animais , Mapeamento Cromossômico , Clonagem Molecular , Cricetinae , Cricetulus , Feminino , Regulação da Expressão Gênica , Humanos , Masculino , Camundongos , Neoplasias/genética , Neoplasias/imunologia , Receptores de Antígenos de Linfócitos T/fisiologia , Linfócitos T/patologiaRESUMO
OBJECTIVE: To determine the relationship between trisomies 13, 18, and 21 and craniofacial malformations detected by prenatal sonography. DESIGN: During a 29-year period (1976 through 2004), prenatal sonographic findings of 69 fetuses with trisomy 13; 171 fetuses with trisomy 18; 302 fetuses with trisomy 21; and 17 fetuses with other trisomies were evaluated retrospectively, after fetal karyotype identification. Sonographic findings were compared with autopsy results in 209 patients (trisomy 13, n=39; trisomy 18, n=64; and trisomy 21, n=106). RESULTS: For trisomy 13, cleft deformities were detected prenatally in 65.2%, and of the 39 cases with pathological information, 76.9% were found to have a cleft deformity. Ocular and orbital abnormalities were found in 28%. Malformations of the jaws and abnormal profiles were more frequently diagnosed postnatally than prenatally. For trisomy 18, abnormal profiles (41.5%) and ear abnormalities (5.3%) were the most noticeable ultrasound markers, next to abnormalities of the neurocranium (36.8%) and cranial bone configuration (21.6%). Dysmorphisms of the eye, ear, or nose were detected more frequently in autopsy cases. For trisomy 21, ultrasound showed an aberrant shape of the skull in 14.2% of fetuses. In general, the ocular-orbital and nasal abnormalities in fetuses with trisomy 18 or 21 were more evident in pathological examination than in prenatal ultrasound imaging. CONCLUSIONS: Facial anomalies are common in the major trisomies, and their prenatal sonographic identification should be improved. The above-mentioned facial anomalies provide sufficient reason to consider performing cytogenic evaluation.
Assuntos
Cromossomos Humanos 13-15/genética , Cromossomos Humanos 16-18/genética , Cromossomos Humanos 21-22 e Y/genética , Anormalidades Craniofaciais/diagnóstico por imagem , Anormalidades Craniofaciais/genética , Anormalidades Maxilofaciais/diagnóstico por imagem , Anormalidades Maxilofaciais/genética , Trissomia/patologia , Ultrassonografia Pré-Natal , Adulto , Amniocentese , Autopsia , Cromossomos Humanos 13-15/diagnóstico por imagem , Cromossomos Humanos 16-18/diagnóstico por imagem , Cromossomos Humanos 21-22 e Y/diagnóstico por imagem , Anormalidades Craniofaciais/patologia , Feminino , Marcadores Genéticos , Idade Gestacional , Humanos , Recém-Nascido , Cariotipagem , Masculino , Idade Materna , Anormalidades Maxilofaciais/patologia , Fenótipo , Estudos Retrospectivos , Crânio/anormalidadesRESUMO
UNLABELLED: Examination of fetal tissue from spontaneous miscarriages shows that 50-70% of them were caused by abnormal karyotype. The most frequent genetic abnormalities include abnormal number of chromosomes, aberration of chromosomes structure and chromosome mosaic anomalies. OBJECTIVE: The aim of the study was to find out whether there is any difference in the frequency of chromosomal aberrations in patients who miscarried for the first time comparing to patients with recurrent miscarriages. MATERIAL AND METHODS: Examination was performed on 129 miscarriage material samples from 128 women. Fluorescent hybridization in-situ (FISH) was used for genetic examination. RESULTS: We received 120 results in which 45 (37,5%) were abnormal. The most frequent chromosomal aberration was trisomy followed by triploidy and monosomy of chromosome X. Among 59 samples from first miscarriage we found 25 abnormal karyotypes. In the 61 samples from the second, third and the next miscarriages we found 20 chromosomal abnormalities. CONCLUSIONS: Frequency of chromosomal aberrations in the tissue from the first miscarriage is significantly higher than in samples from second or following miscarriages, which means that genetic factors are less likely to induce recurrent miscarriages. Genetic results confirm that most chromosomal abnormalities arise de-novo.
Assuntos
Aborto Espontâneo/genética , Aneuploidia , Aberrações Cromossômicas/estatística & dados numéricos , Cromossomos Humanos/genética , Adulto , Córion/patologia , Cromossomos Humanos 13-15/genética , Cromossomos Humanos 16-18/genética , Cromossomos Humanos 21-22 e Y/genética , Feminino , Humanos , PolôniaRESUMO
OBJECTIVE: Genetic factors are the most common causes of spontaneous abortions. 50% to 80% of first-trimester abortions reveal-chromosome abnormalities. Evidence for the recurrence of the same or another chromosome abnormality in the next pregnancy is scarce. THE AIM: The aim of our study was to estimate recurrence risk of abortus aneuploidy and to find out whether karyotyping of the abortus allows the prognose subsequent pregnancy outcomes. MATERIAL AND METHODS: Paraffin-embedded chorions have undergone cytogenetic examination using FISH with chromosome-specific probes. 57 chorions from 26 women have been assessed, including chorions from two consecutive abortions from 18 women and chorions from three consecutive abortions from 5 women. RESULTS: 38.6% of 57 specimens had chromosome aberrations. The most prevalent anomalies were 16, 21 and 18 trisomies. 23 patients had a subsequent abortion karyotyped; 15 had a normal initial karyotype and 8 had an aberrant initial karyotype. 3 out of the 8 patients had a repeated chromosome anomaly 5 out of the 15 patients who initially miscarried an aneuploid embryo, had a subsequent miscarriage of an aneuploid embryo. Only 3 (13.04%) out of the 23 patients displayed aneuploidy in each abortus. CONCLUSION: (1) Chromosome aberrations can reappear in subsequent pregnancies in the same patient and may be the cause of recurrent miscarriages. (2) The value of embryo/fetal karyotyping is not decisive in prognosis of subsequent pregnancy outcome. (3) Abnormal fetal karyotype can occur regardless of other causes of pregnancy loss.
Assuntos
Aborto Habitual/genética , Aneuploidia , Aberrações Cromossômicas , Cromossomos Humanos 13-15/genética , Cromossomos Humanos 16-18/genética , Cromossomos Humanos 21-22 e Y/genética , Córion/patologia , Feminino , Humanos , Cariotipagem , Gravidez , Aberrações dos Cromossomos Sexuais , Trissomia/genéticaRESUMO
BACKGROUND AND OBJECTIVES: Genetic testing is recommended for individuals with autism spectrum disorder (ASD). Pathogenic yield varies by clinician and/or patient characteristics. Our objectives were to determine the pathogenic yield of genetic testing, the variability in rate of pathogenic results based on subject characteristics, and the percentage of pathogenic findings resulting in further medical recommendations in toddlers with a Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition diagnosis of ASD. METHODS: We conducted a retrospective chart review of 500 toddlers, 18 to 36 months, diagnosed with Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition ASD (mean age: 25.8 months, 79% male). Subject demographics, medical and neuropsychological characteristics, and genetic test results were abstracted. Genetic results were divided into negative or normal, variants of unknown significance, and pathogenic. Subject characteristics were compared across results. Manual chart review determined if further recommendations were made after pathogenic results. RESULTS: Over half of subjects (59.8%, n = 299) completed genetic testing, and of those, 36 (12.0%) had pathogenic findings. There were no significant differences in Bayley Scales of Infant Development cognitive (P = .112), language (P = .898), or motor scores (P = .488) among children with negative or normal findings versus a variant of unknown significance versus pathogenic findings. Medical recommendations in response to the genetic finding were made for 72.2% of those with pathogenic results. CONCLUSIONS: Our findings reinforce the importance of genetic testing for toddlers diagnosed with ASD given the 12% yield and lack of phenotypic differences between subjects with and without pathogenic findings. The majority of pathogenic results lead to further medical recommendations.
Assuntos
Transtorno do Espectro Autista/genética , Testes Genéticos/estatística & dados numéricos , Transtorno do Espectro Autista/diagnóstico , Transtornos Dismórficos Corporais/diagnóstico , Transtornos Dismórficos Corporais/genética , Pré-Escolar , Cromossomos Humanos 13-15 , Cognição , Manual Diagnóstico e Estatístico de Transtornos Mentais , Feminino , Proteína do X Frágil da Deficiência Intelectual/genética , Deleção de Genes , Duplicação Gênica , Testes Genéticos/métodos , Humanos , Lactente , Desenvolvimento da Linguagem , Masculino , Análise em Microsséries , Mosaicismo , Destreza Motora , Mutação , Fenótipo , Encaminhamento e Consulta , Estudos RetrospectivosRESUMO
Linkage analysis in families with apparent autosomal dominant reading disability produced a lod score of 3.241. Since the traditionally accepted significance level for linkage is a lod score of 3.0, these results strongly suggest that a gene playing a major etiologic role in one form of reading disability is on chromosome 15.
Assuntos
Cromossomos Humanos 13-15 , Dislexia/genética , Ligação Genética , Humanos , LinhagemRESUMO
Two rare cases of chronic lymphocytic leukemia (CLL) in children have been studied; both are associated with a previously undescribed chromosomal translocation [t(2;14) (p13;q32)]. In one patient the translocation was reciprocal and the breakpoint on chromosome 14 occurred just 5' of the C gamma 2 region on the productive immunoglobulin heavy-chain allele. The breakpoint on chromosome 2 does not involve the K locus but lies within an uncharacterized region that coincides with the position of a constitutive fragile site that occurs within normal lymphocytes. Data on the second patient are consistent with these findings and suggest that these cases represent a rare but distinct subgroup of CLL's with a specific cytogenetic change.
Assuntos
Cromossomos Humanos 1-3 , Cromossomos Humanos 13-15 , Leucemia Linfoide/genética , Translocação Genética , Alelos , Criança , Sítios Frágeis do Cromossomo , Fragilidade Cromossômica , Mapeamento Cromossômico , Humanos , Imunoglobulina M/genética , Recombinação GenéticaRESUMO
Genetic polymorphism has been demonstrated in man for many characteristics including blood groups, serum proteins, tissue enzymes, and hemoglobins. A class of chromosomal polymorphism involving constitutive heterochromatin has now been found. Through the use of a special technique that permits visualization of heterochromatin, seven heterochromatin variants have been found among four individuals. These results suggest a very high frequency of variability of heterochromatin in the population.
Assuntos
Heterocromatina , Polimorfismo Genético , Cromossomos Humanos 1-3 , Cromossomos Humanos 13-15 , Cromossomos Humanos 16-18 , Cromossomos Humanos 19-20 , Cromossomos Humanos 21-22 e Y , Cromossomos Humanos 6-12 e X , DNA , Humanos , Linfócitos , Métodos , Desnaturação de Ácido Nucleico , Renaturação de Ácido NucleicoRESUMO
Burkitt lymphoma cells carrying either a rearranged or unrearranged c-myc oncogene were examined with the use of probes from the 5' exon and for the second and third exon of the oncogene. The results indicate that the normal c-myc gene on chromosome 8 and the 5' noncoding and 3' coding segments of the c-myc oncogene separated by the chromosomal translocation are under different transcriptional control in the lymphoma cells. Burkitt lymphoma cells carrying a translocated but unrearranged c-myc oncogene express normal c-myc transcripts. In contrast, lymphoma cells carrying a c-myc gene rearranged head to head with the immunoglobulin constant mu region gene express c-myc transcripts lacking the normal untranslated leader.
Assuntos
Linfoma de Burkitt/genética , Oncogenes , Cromossomos Humanos 13-15 , Cromossomos Humanos 19-20 , Cromossomos Humanos 6-12 e X , Regulação da Expressão Gênica , Genes , Humanos , Cadeias Pesadas de Imunoglobulinas/genética , Óperon , Transcrição Gênica , Translocação GenéticaRESUMO
Although a constitutional chromosomal deletion including 13q14 has been found to date in all retinoblastoma patients whose esterase D activity is 50 percent of normal, one female patient has been found who has 50 percent esterase D activity in all normal cells examined but no deletion of 13q14 at the 550-band level. Therefore, she has the smallest constitutional chromosomal deletion within 13q14 that is associated with susceptibility to retinoblastoma. Two stem lines were identified in a retinoblastoma from this patient, and each one had a missing 13 chromosome. No detectable esterase D activity was found in the tumor, indicating that the normal nondeleted 13 chromosome was lost in both stem lines. Thus the data from this patient not only show that there is a total loss of genetic information at the location of the retinoblastoma gene within the tumor, but also imply that recessive genes may play an important role in the development of certain human tumors including retinoblastoma.
Assuntos
Cromossomos Humanos 13-15 , Retinoblastoma/genética , Pré-Escolar , Deleção Cromossômica , DNA de Neoplasias/genética , Feminino , Genes Recessivos , Humanos , CariotipagemRESUMO
Evaluation of three families with hereditary retinoblastoma demonstrates close linkage of the gene for this tumor with the genetic locus for esterase D. These results assign the gene for the hereditary form of retinoblastoma to band q14 on chromosome 13, the same region which is affected in the chromosome deletion form of this eye tumor, and therefore suggest a common underlying mechanism in the pathogenesis of these two forms of retinoblastoma.