RESUMEN
A large 10-generation family with late-onset Alzheimer disease (LOAD) inherited as an autosomal dominant trait was evaluated historically, clinically, and genetically. The family origin was traced to a founder couple of French ancestry with approximately 3,000 descendants. Although the transmission of a genetic predisposition to LOAD is demonstrated through male individuals, a predominance of affected women is observed. Currently, 14 individuals, 12 of whom are women, are classified as affected with Alzheimer disease (AD). Among the affected, the age of onset ranged from 55 to 78 years. Genotyping of the apolipoprotein E (APOE) locus demonstrated that homozygotes for the E4 allele (APOE4) developed signs of AD in their late 60s, whereas affected heterozygotes presented with the disease in their 70s. A significantly higher APOE4 frequency was observed in affected family members than in those unaffected (0.79 vs. 0.25, chi 2 = 9.919, p = 0.0016, df = 1). Survival for more than 15 years after diagnosed onset was observed in a number of those affected and can be attributed to an improved environment, including excellent care and management during the disabling phase of illness. Alternatively, it may be an example of the genetic heterogeneity in AD. Complete documentation of large families such as the one presented will facilitate the discovery of the multiple genetic factors involved in the pathogenesis of AD.
Asunto(s)
Enfermedad de Alzheimer/genética , Anciano , Anciano de 80 o más Años , Alelos , Enfermedad de Alzheimer/diagnóstico , Enfermedad de Alzheimer/mortalidad , Enfermedad de Alzheimer/psicología , Apolipoproteína E4 , Apolipoproteínas E/genética , Aberraciones Cromosómicas/genética , Trastornos de los Cromosomas , Evaluación de la Discapacidad , Femenino , Frecuencia de los Genes , Genes Dominantes/genética , Tamización de Portadores Genéticos , Marcadores Genéticos/genética , Evaluación Geriátrica , Homocigoto , Humanos , Masculino , Persona de Mediana Edad , Linaje , Análisis de SupervivenciaRESUMEN
Fluorescence in situ hybridization (FISH) and the reverse transcription-polymerase chain reaction (RT-PCR) were used to examine a patient presenting with acute myelogenous leukemia (AML) FAB M2, and a complex t(4;9;22)(p14;q34;q11.2). The patient's clinical course was characterized by an aggressive leukemia, resistant to intensive therapy including allogeneic bone marrow transplantation. FISH analysis, using two chromosome painting probes and a BCR/ABL specific probe, confirmed the cytogenetic observation of a 22q11.2-->4p14 and a 4p14-->9q34 exchange, and revealed the presence of a 9q34-->22q11.2, respectively. In addition, RT-PCR demonstrated the presence of a BCR/ABL transcript derived from the major breakpoint cluster region (M-bcr) of the BCR gene. This transcript has been shown to generate an active 210 kDa tyrosine kinase protein more commonly observed in chronic myelogenous leukemia. Because the presentation of AML with this ABL-->BCR fusion product is a rare event, it would seem likely that the additional complex chromosomal rearrangement involving chromosomes 4, 9, and 22 played a role in the aggressive presentation and clinical behavior of this patient's leukemia.
Asunto(s)
Cromosomas Humanos Par 22/genética , Cromosomas Humanos Par 4/genética , Cromosomas Humanos Par 9/genética , Leucemia Mieloide Aguda/genética , Translocación Genética/genética , Adulto , Antígenos CD/análisis , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Trasplante de Médula Ósea , Terapia Combinada , Proteínas de Fusión bcr-abl/análisis , Humanos , Hibridación Fluorescente in Situ , Leucemia Mieloide Aguda/inmunología , Leucemia Mieloide Aguda/terapia , Masculino , Cromosoma FiladelfiaRESUMEN
BACKGROUND: Renal medullary carcinoma is a newly described, aggressive kidney tumor. All patients with the disease have been African-American with sickle cell (SC) trait or hemoglobin SC disease. METHODS: Patient information was obtained from individual patient records and from the Department of Defense national data bank, The Defense Enrollment and Eligibility Reporting System. Data were obtained from either personal review of the patient's records or from discussion with the patient's physician. Cytogenetic studies were performed on one patient. RESULTS: Six patients are presented. All had SC trait. Median age was 24.5 years and 1 patient was female. Time from diagnosis to death averaged 3 months (range 1-7 mos). No objective responses were reported to a wide variety of chemo and immunotherapies: cyclophosphamide, doxorubicin, cisplatin; methotrexate, vinblastine, doxorubicin, and cisplatin; single agent interferon; single agent paclitaxel; or single agent vinblastine. Investigational regimens included topotecan, doxorubicin, and filgrastim; alpha-interferon, interleukin-2, and 5-fluorouracil; and single agent paclitaxel. Cytogenetic studies revealed numerous structural, as well as numerical anomalies. Of the cells successfully karyotyped (n=4), 2 contained abnormalities of chromosome 3 and all contained monosomy 11. CONCLUSIONS: Renal medullary carcinoma is an aggressive, chemoresistant tumor. Time from discovery of tumor to patient death is very short and has been altered by a wide variety of chemotherapies and immunotherapies. An unidentified genetic component is likely present.
Asunto(s)
Carcinoma Medular , Neoplasias Renales , Adulto , Factores de Edad , Población Negra , Carcinoma Medular/tratamiento farmacológico , Carcinoma Medular/genética , Carcinoma Medular/patología , Aberraciones Cromosómicas/genética , Trastornos de los Cromosomas , Femenino , Humanos , Cariotipificación , Neoplasias Renales/tratamiento farmacológico , Neoplasias Renales/genética , Neoplasias Renales/patología , Masculino , Rasgo Drepanocítico/complicacionesAsunto(s)
Síndrome de Prader-Willi/diagnóstico , Adulto , Deleción Cromosómica , Cromosomas Humanos Par 15 , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/genética , Marcadores Genéticos/genética , Humanos , Hibridación Fluorescente in Situ , Masculino , Síndrome de Prader-Willi/genéticaAsunto(s)
Cromosomas Humanos Par 8 , Computadores , Bases de Datos Bibliográficas , Asesoramiento Genético , Trisomía , Adulto , Células Cultivadas , Cromosomas Humanos Par 10 , Cromosomas Humanos Par 17 , Femenino , Humanos , Recién Nacido , Cariotipificación , Masculino , Embarazo , Piel/patología , Translocación GenéticaRESUMEN
Gradual refinements in chromosome technology over the years have enabled biologists to study the chromosomes at the molecular level. An account of the development of a computerized technique for cataloguing all structural and numerical aberrations in human chromosomes and setting up of registries of abnormal human karyotypes for delineation of karyotype-phenotype relationship for future use has been emphasized in the present paper.
Asunto(s)
Aberraciones Cromosómicas , Bases de Datos Bibliográficas , Sistemas en Línea , Sistema de Registros , Humanos , Cooperación InternacionalRESUMEN
A case of tetrasomy i(12p) detected prenatally is reported. The patient, a black, 32-year-old G3P2002 at 24 weeks' gestation with an unremarkable family history presented herself for prenatal care. Ultrasound examination showed a fetus with diminished femoral and humeral lengths, and hydramnios. A level II scan confirmed the presence of an omphalocele. Amniocentesis at 31 weeks showed 47,XY,+i(12p) karyotype. An infant with multiple congenital anomalies was delivered at 34 weeks. The infant died after 5 h. Genetic and ultrasonographic examinations in the third trimester were helpful in the investigation of this fetus with multiple congenital anomalies. The careful, complete team counselling afforded by this approach enabled the mother and family to be well adjusted to the strong possibility (and subsequent reality) of an abnormal infant.
Asunto(s)
Diagnóstico Prenatal , Aberraciones Cromosómicas Sexuales/genética , Cromosoma X , Cromosoma Y , Adulto , Autorradiografía , Cara/anomalías , Femenino , Humanos , Cariotipificación/métodos , Hibridación de Ácido Nucleico , Trastornos de la Pigmentación , Poliploidía , Embarazo , Aberraciones Cromosómicas Sexuales/diagnóstico , Tórax/anomalíasAsunto(s)
Ética Médica , Eutanasia Pasiva , Eutanasia , Asesoramiento Genético , Pruebas Genéticas , HumanosAsunto(s)
Cromosomas Humanos 13-15 , Trisomía , Femenino , Humanos , Recién Nacido , Cariotipificación , Masculino , Fenotipo , SíndromeRESUMEN
Segregation analysis of the offspring of balanced translocation carriers was performed on 327 pedigrees collated from published sources and personal communications. Correction was made for bias of ascertainment. Translocations studied involved chromosome arms 1p, 4q, 6p, 6q, 7p, 8p, 10p, 10q, 11q, 14q, 16q, and 17p. Findings included similar rates of occurrence of abnormal liveborn offspring in male and female carriers except for a reduction of risk in male carriers of translocations segregating by 3:1 mode; an elevated risk of fetal loss (spontaneous abortions and stillbirths) in female carriers of 6q, 11q, and 16q translocations compared to male carriers of these translocations; a fetal loss rate exceeding general population estimates in female carriers of 6q and 10q translocations and in male carriers of 6p, 8p, 10q, and 14q translocations including a rate of nearly 50% among female 6q translocation carriers; a higher than expected number of balanced carriers among liveborn offspring; and a low risk of abnormal liveborn children among carriers ascertained by means other than through unbalanced probands. We propose that some translocation carriers may be helped by consideration of more specific empiric risk figures than have traditionally been used.