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1.
Pediatr Dermatol ; 32(2): 263-6, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-24920397

RESUMO

A 6-year-old girl presented for evaluation of skin discoloration. Examination revealed oval and oblong hypopigmented macules on her trunk and extremities. Cytogenetic studies and immunohistochemistry of biopsies from normally pigmented and hypopigmented skin revealed mosaicism for partial tetrasomy for 13q with low melanocyte levels in lesional skin. The patient was diagnosed with phylloid hypomelanosis (PH), a distinct clinical entity linked to abnormalities in chromosome 13. This article reviews the literature regarding PH and supports the notion that mosaicism of the melanocyte region of chromosome 13q is responsible for PH.


Assuntos
Anormalidades Múltiplas/diagnóstico , Cromossomos Humanos Par 13 , Hipopigmentação/genética , Mosaicismo , Tetrassomia/genética , Anormalidades Múltiplas/genética , Biópsia por Agulha , Criança , Citogenética , Feminino , Seguimentos , Humanos , Hipopigmentação/diagnóstico , Imuno-Histoquímica , Hibridização In Situ , Doenças Raras , Tetrassomia/diagnóstico
2.
Am J Hum Genet ; 87(4): 465-79, 2010 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-20887964

RESUMO

By defining the chromosomal breakpoint of a balanced t(10;12) translocation from a subject with Kallmann syndrome and scanning genes in its vicinity in unrelated hypogonadal subjects, we have identified WDR11 as a gene involved in human puberty. We found six patients with a total of five different heterozygous WDR11 missense mutations, including three alterations (A435T, R448Q, and H690Q) in WD domains important for ß propeller formation and protein-protein interaction. In addition, we discovered that WDR11 interacts with EMX1, a homeodomain transcription factor involved in the development of olfactory neurons, and that missense alterations reduce or abolish this interaction. Our findings suggest that impaired pubertal development in these patients results from a deficiency of productive WDR11 protein interaction.


Assuntos
Cromossomos Humanos Par 10/genética , Proteínas de Homeodomínio/genética , Hipogonadismo/genética , Síndrome de Kallmann/genética , Proteínas de Membrana/genética , Proteínas Proto-Oncogênicas/genética , Puberdade/genética , Fatores de Transcrição/genética , Translocação Genética/genética , Adolescente , Animais , Humanos , Immunoblotting , Imuno-Histoquímica , Imunoprecipitação , Hibridização In Situ , Hibridização in Situ Fluorescente , Masculino , Proteínas de Membrana/metabolismo , Camundongos , Análise em Microsséries , Mutação de Sentido Incorreto/genética , Polimorfismo de Nucleotídeo Único/genética , Proteínas Proto-Oncogênicas/metabolismo , Ratos , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Técnicas do Sistema de Duplo-Híbrido , Peixe-Zebra
3.
Pediatr Blood Cancer ; 59(2): 254-7, 2012 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-22012708

RESUMO

BACKGROUND: The laboratory and clinical benefits of hydroxyurea therapy for children with sickle cell anemia (SCA) are well recognized, but treatment in young patients is limited in part by concerns about long-term genotoxicity, and specifically possible carcinogenicity. PROCEDURE: The Pediatric Hydroxyurea Phase III Clinical Trial (BABY HUG) was a multicenter double-blinded placebo-controlled randomized clinical trial (NCT00006400) testing whether hydroxyurea could prevent chronic organ damage in very young patients with SCA. An important secondary objective was the measurement of acquired genotoxicity using three laboratory assays: chromosomal karyotype, illegitimate VDJ recombination events, and micronucleated reticulocyte formation. RESULTS: Our data indicate that hydroxyurea treatment was not associated with any significant increases in genotoxicity compared to placebo treatment. CONCLUSIONS: These data provide additional support to the safety profile of hydroxyurea for young patients with SCA, and suggest that genotoxicity in this patient population is low.


Assuntos
Anemia Falciforme/tratamento farmacológico , Anemia Falciforme/genética , Antidrepanocíticos/uso terapêutico , Dano ao DNA/efeitos dos fármacos , Dano ao DNA/genética , Hidroxiureia/uso terapêutico , Método Duplo-Cego , Seguimentos , Humanos , Lactente , Prognóstico , Recombinação V(D)J
4.
Nucleic Acids Res ; 37(20): 6746-53, 2009 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-19759212

RESUMO

Mammalian cells repair DNA double-strand breaks (DSBs) via efficient pathways of direct, nonhomologous DNA end joining (NHEJ) and homologous recombination (HR). Prior work has identified a complex of two polypeptides, PSF and p54(nrb), as a stimulatory factor in a reconstituted in vitro NHEJ system. PSF also stimulates early steps of HR in vitro. PSF and p54(nrb) are RNA recognition motif-containing proteins with well-established functions in RNA processing and transport, and their apparent involvement in DSB repair was unexpected. Here we investigate the requirement for p54(nrb) in DSB repair in vivo. Cells treated with siRNA to attenuate p54(nrb) expression exhibited a delay in DSB repair in a gamma-H2AX focus assay. Stable knockdown cell lines derived by p54(nrb) miRNA transfection showed a significant increase in ionizing radiation-induced chromosomal aberrations. They also showed increased radiosensitivity in a clonogenic survival assay. Together, results indicate that p54(nrb) contributes to rapid and accurate repair of DSBs in vivo in human cells and that the PSF.p54(nrb) complex may thus be a potential target for radiosensitizer development.


Assuntos
Quebras de DNA de Cadeia Dupla , Reparo do DNA , Proteínas Associadas à Matriz Nuclear/metabolismo , Fatores de Transcrição de Octâmero/metabolismo , Proteínas de Ligação a RNA/metabolismo , Tolerância a Radiação , Sobrevivência Celular , Aberrações Cromossômicas , Proteínas de Ligação a DNA , Células HeLa , Humanos , RNA Interferente Pequeno/metabolismo
5.
Am J Med Genet A ; 146A(17): 2234-41, 2008 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-18666229

RESUMO

Approximately, 20 cases of interstitial deletions of 9q have been reported in the literature spanning the breakpoints from 9q21 to 9q34. Unlike the 9q subtelomeric deletions, the interstitial deletions do not demonstrate a specific recognizable phenotype, although the majority of patients had microcephaly. Lack of precise molecular delineation of the extent of deletions in the published cases makes it difficult to develop an accurate genotype-phenotype correlation. We report on fine mapping of breakpoints using the Affymetrix Human Mapping 500K Array Set in two unrelated female patients with overlapping de novo deletion in 9q. SNP oligonucleotide microarray analysis (SOMA) indicated these to be relatively large deletions with Patient 1 having a 6.47 Mb deletion (>60 genes) spanning 9q32-q33.2 and Patient 2 having a 9.68 Mb deletion (>20 genes) localized to 9q31.1-q33.1. FISH analysis with BAC clones localized to the breakpoints showed discrepant results in Patient 1. Based on the review of previously reported interstitial 9q deletion patients and our patients, the minimal region of overlap (MRO) appears to encompass the 9q32 region and a phenotype characterized by microcephaly, neurological dysfunction and facial dysmorphism can be deduced. Our study shows the investigative nature of the latest array technology and the limitations of this technology in the accurate delineation of breakpoints.


Assuntos
Anormalidades Múltiplas/genética , Quebra Cromossômica , Deleção Cromossômica , Cromossomos Humanos Par 9/genética , Face/anormalidades , Pré-Escolar , Mapeamento Cromossômico , Deficiências do Desenvolvimento/genética , Feminino , Humanos , Hibridização in Situ Fluorescente , Lactente , Cariotipagem , Microcefalia/genética , Análise de Sequência com Séries de Oligonucleotídeos , Fenótipo , Polimorfismo de Nucleotídeo Único
7.
Cancer Genet Cytogenet ; 177(2): 135-8, 2007 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-17854669

RESUMO

A 22-year-old woman presented with lymphadenopathy in a similar manner as she had presented at age 4. At age 4, she was diagnosed with acute myelogenous leukemia (AML) with t(18;22)(q23;q11.2) and received chemotherapy until age 6 under a pediatric study protocol. At age 22, a lymph node biopsy confirmed granulocytic sarcoma, and a bone marrow aspirate showed increased myeloblasts with no dysplasia. Cytogenetic analyses of the lymph node and the bone marrow were positive for t(18;22)(q23;q11.2). The patient was treated for relapsed AML and at writing had been disease-free for 9 months. Translocation between chromosomes 18 and 22 has been reported in indolent lymphoproliferative disorders, but not in AML. Although we do not know the precise molecular etiology of this leukemia, the uncommon presentation for AML and late relapse with the same chromosomal abnormality may indicate a causal relationship between this novel chromosomal abnormality and the AML. This observation also suggests the possible presence of dormant stem cells containing the chromosomal abnormality in this particular patient.


Assuntos
Aberrações Cromossômicas , Cromossomos Humanos Par 18/genética , Cromossomos Humanos Par 22/genética , Leucemia Mieloide Aguda/genética , Recidiva Local de Neoplasia/genética , Adolescente , Pré-Escolar , Feminino , Humanos , Hibridização in Situ Fluorescente , Cariotipagem , Leucemia Mieloide Aguda/patologia , Recidiva Local de Neoplasia/patologia
8.
Am J Med Genet ; 113(4): 367-70, 2002 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-12457409

RESUMO

We report a patient with a mosaic karyotype resulting from an adjacent 1 segregation of the familial autosomal translocation (11;22). The karyotype seen in fibroblast is 46,XY,der(22)t(11;22)(q23.3;q11.2)/46,XY. No evidence of the abnormal cell line was seen in the cultures obtained from the lymphocytes. The clinical phenotype of the patient does not fit a particular pattern of partial monosomy 22 or partial trisomy 11. There are some features that have been previously reported in patients with trisomy 11q23 --> qter. The mosaic karyotype in our patient could be a result of a series of postzygotic mitotic events of a zygote carrying the der(22) chromosome. These mechanisms involve events that are well documented for several chromosomes. This case underscores the necessity of performing exhaustive cytogenetic analysis in patients with an abnormal phenotype with a family history of a chromosome rearrangement in fibroblast cells if lymphocyte analysis is normal.


Assuntos
Anormalidades Múltiplas/genética , Segregação de Cromossomos , Cromossomos Humanos Par 11 , Cromossomos Humanos Par 22 , Mosaicismo , Translocação Genética , Anormalidades Múltiplas/patologia , Adulto , Fibroblastos/metabolismo , Humanos , Cariotipagem , Masculino , Linhagem , Pele/citologia
9.
Ethn Dis ; 12(1): S1-68-71, 2002.
Artigo em Inglês | MEDLINE | ID: mdl-11913624

RESUMO

OBJECTIVES: An angiotensin II type I receptor polymorphism (AGTR1/A1166C) was previously found to be associated with hypertension. The purpose of this study was to investigate the relationship between this polymorphism and resting measures of hemodynamics in normotensive youth. DESIGN: Subjects were 41 Whites (mean +/- SD: 18 +/- 3 y old, 26 males) and 73 Blacks (19 +/- 2 y old, 55 males) with a positive family history of hypertension. METHODS: Hemodynamic measures included resting systolic blood pressure (SBP), diastolic blood pressure (DBP), and heart rate (HR). RESULTS: Allele frequencies were significantly different (chi2 = 14.10, P < or = .001) between Whites and Blacks (.23 vs .06 for the C allele, respectively). For all subsequent analyses, subjects were categorized into two genotype groups, carriers and non-carriers of the C allele, because only two Whites and no Blacks were homozygous for the C allele. Genotype frequencies were significantly different (chi2 = 12.66, P < or = .0011) between Whites and Blacks (.41 vs .12 for the carriers, respectively). Among Whites, univariate analyses of covariance, using body mass index and age as covariates, indicated that carriers of the C allele compared to non-carriers, had a higher DBP (61.6 +/- 6.7 vs 57.8 +/- 6.2 mm Hg, P < or = .05) and HR (68.0 +/- 10.5 vs 61.1 +/- 8.1, P < or = .05). Genotype was not associated with resting hemodynamic measures in Blacks (all P values > .05). CONCLUSIONS: These results are consistent with findings that have typically involved White adults, and demonstrate that the renin system does not seem to play as great a role in BP control in Blacks as it does in Whites.


Assuntos
População Negra/genética , Pressão Sanguínea/genética , Hemodinâmica/genética , Polimorfismo Genético , Receptores de Angiotensina/genética , População Branca/genética , Adolescente , Adulto , Alelos , Análise de Variância , Pressão Sanguínea/fisiologia , Determinação da Pressão Arterial/métodos , Índice de Massa Corporal , Estudos de Coortes , Feminino , Genótipo , Humanos , Estudos Longitudinais , Masculino , Probabilidade , Receptor Tipo 1 de Angiotensina , Receptores de Angiotensina/análise , Descanso , Sensibilidade e Especificidade
10.
Leuk Res ; 34(7): 954-7, 2010 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-20138360

RESUMO

Aneuploidy is a very common prognostic factor in multiple myeloma (MM). Nonhyperdiploidy including near-tetraploidy (NT) is a poor prognostic indicator, compared to hyperdiploidy in multiple myeloma (MM). NT results from endoduplication of hypodiploidy. We report of a 55-year-old female patient diagnosed with advanced stage MM with hyperdiploidy and t(8;14)(q24;q32). The patient responded well to lenalidomide and dexamethasone for approximately 1 year. At the time of progression, she had become unresponsive to lenalidomide and subsequently bortezomib, and was found to have NT and loss of choromosome 13. There is another reported patient who had a possible interchange from nonhyperdiploidy to hyperdiploidy status, however, artifact could not be ruled out. To our knowledge, this is the first patient in whom evolution of an abnormal clone from a hyperdiploidy to a NT abnormal clone has been confirmed during the natural course of MM. This evolution is associated with resistance to novel drugs and poor prognosis in MM.


Assuntos
Inibidores da Angiogênese/farmacologia , Antineoplásicos/farmacologia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Ácidos Borônicos/farmacologia , Deleção Cromossômica , Resistencia a Medicamentos Antineoplásicos/genética , Mieloma Múltiplo/genética , Células-Tronco Neoplásicas/efeitos dos fármacos , Poliploidia , Inibidores de Proteases/farmacologia , Pirazinas/farmacologia , Talidomida/análogos & derivados , Inibidores da Angiogênese/uso terapêutico , Ácidos Borônicos/administração & dosagem , Bortezomib , Cromossomos Humanos Par 13 , Cromossomos Humanos Par 14/ultraestrutura , Cromossomos Humanos Par 8/ultraestrutura , Células Clonais/efeitos dos fármacos , Células Clonais/ultraestrutura , Terapia Combinada , Dexametasona/administração & dosagem , Feminino , Humanos , Cariotipagem , Lenalidomida , Pessoa de Meia-Idade , Mieloma Múltiplo/tratamento farmacológico , Mieloma Múltiplo/patologia , Mieloma Múltiplo/cirurgia , Células-Tronco Neoplásicas/ultraestrutura , Transplante de Células-Tronco de Sangue Periférico , Inibidores de Proteases/uso terapêutico , Pirazinas/administração & dosagem , Talidomida/administração & dosagem , Talidomida/farmacologia , Translocação Genética , Transplante Autólogo
11.
Int J Clin Exp Pathol ; 3(7): 718-22, 2010 Aug 17.
Artigo em Inglês | MEDLINE | ID: mdl-20830243

RESUMO

Trisomy 10 as the sole cytogenetic abnormality in AML is rare, with an incidence rate of < 0.5%. It tends to affect the elderly and is extremely rare in pediatric patients. We describe a case of an 8-month-old Caucasian baby who presented with prominence of left eye and fever without lymphadenopathy or hepatosplenomegaly. Bone survey showed diffuse periosteal reaction in the femur, pelvis, maxillary and orbital bones (with fracture). CBC revealed normal white blood cell count with increased blasts, mild anemia and moderate thrombocytopenia. Bone marrow biopsy showed increased myeloblasts with bilineage dysplasia and 3-4+ reticulin fibrosis. Flow cytometry revealed blasts positive for CD34, CD33, and MPO and negative for CD7, CD13, and HLA-DR. Trisomy 10 was demonstrated by chromosome analysis and fluorescence in-situ hybridization. The patient received induction chemotherapy and achieved complete clinical and hematologic remission at day 28. However, he relapsed after three cycles of chemotherapy. Compared to the two other reported pediatric cases, our patient has some unique features such as much younger age and additional findings such as bilineage dysplasia and bone marrow fibrosis. Both reported cases and our case were classified as AML-M2 indicating that this may be a common subtype in pediatric patients. Bone involvement was present in our patient and one other case and both had similar immunophenotype (CD33+, CD7-). These findings suggest that isolated trisomy 10 may be associated with distinct clinicopathologic features in pediatric AML. Studies on additional patients are needed to establish this association.


Assuntos
Cromossomos Humanos Par 10/genética , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/patologia , Trissomia/genética , Trissomia/patologia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Separação Celular , Aberrações Cromossômicas , Citometria de Fluxo , Humanos , Imuno-Histoquímica , Hibridização in Situ Fluorescente , Lactente
12.
Cancer Genet Cytogenet ; 202(2): 129-32, 2010 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-20875875

RESUMO

Patients with various hematologic malignancies, including acute lymphoblastic leukemia (ALL), acute myeloblastic leukemia (AML), diffuse histiocytic lymphoma, and granulocytic sarcoma, have sometimes been shown to carry the PICALM-MLLT10 fusion gene (alias CALM-AF10) by various cytogenetic methodologies. Cases with the PICALM-MLLT10 fusion gene can involve a diagnostic dilemma for the following reasons: (1) the fusion gene occurs very rarely, (2) the cases do not have a distinct myeloid or lymphoid morphology and cells often appear immature, (3) cases usually have a mixed T-cell and myeloid phenotype, and (4) cases often have a mixed clinical presentation (e.g., mediastinal mass in a patient with AML). A 27-year-old woman was diagnosed with AML with the PICALM-MLLT10 fusion gene. The patient was treated on an AML regimen and achieved a complete remission. Although the reported treatment of these patients varies greatly, outcome remains very poor in the vast majority. Furthermore, central nervous system involvement at diagnosis and relapse are reported in pediatric populations. Routine acute leukemia fluorescence in situ hybridization panels do not include a probe for the PICALM-MLLT10 fusion gene, and therefore diagnosis can be made only when karyotyping is available; that delay can result in initial misdiagnosis and mistreatment. The case report and literature review here (including discussion of the poor prognosis and of management, including CNS prophylaxis) are intended to raise awareness and to inform about PICALM-MLLT10 in acute leukemia.


Assuntos
Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/terapia , Proteínas de Fusão Oncogênica/genética , Adulto , Crise Blástica/genética , Crise Blástica/patologia , Células da Medula Óssea/patologia , Feminino , Humanos , Hibridização in Situ Fluorescente , Cariotipagem , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/patologia
13.
Fertil Steril ; 91(3): 791-7, 2009 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-18555994

RESUMO

OBJECTIVE: To characterize the phenotypic spectrum of males with bilaterally descended testes and a 45,X/46,X,(r)Y karyotype. DESIGN: Retrospective review of patient records; cytogenetic and molecular analysis. SETTING: Tertiary medical center setting. PARTICIPANT(S): Five males, two prepubertal and three postpubertal, with a 45,X/46,X(r)Y karyotype and bilaterally descended testes. INTERVENTION(S): Linear growth evaluation, testicular endocrine and exocrine studies, cytogenetic and molecular analysis on each patient. MAIN OUTCOME MEASURE(S): Clinical phenotype versus genotype. RESULT(S): Both prepubertal males had short stature and low testosterone. All three adults had normal puberty and normal testosterone levels. Two of the adults (one with short stature and one with normal stature) had elevated gonadotropins and azoospermia. The third adult had normal stature, severe oligospermia, normal gonadotropins, and normal serum testosterone. CONCLUSION(S): The phenotypic spectrum of males with a 45,X/46,X(r)Y karyotype and bilaterally descended testes varies greatly from males with short stature and spermatogenic failure to males without short stature and less severely affected spermatogenesis. This broad spectrum of phenotypic findings needs to be taken into account when the clinical geneticist encounters a prenatal diagnosis of a 45,X/46,X(r)Y karyotype. This information will also be helpful for pediatric and reproductive endocrinologists in counseling males with bilaterally descended testes and a 45,X/46,X(r)Y karyotype.


Assuntos
Cromossomos Humanos Y , Disgenesia Gonadal 46 XY/genética , Disgenesia Gonadal Mista/genética , Cromossomos em Anel , Testículo/fisiopatologia , Adulto , Azoospermia/genética , Azoospermia/fisiopatologia , Tamanho Corporal/genética , Criança , Genótipo , Disgenesia Gonadal 46 XY/complicações , Disgenesia Gonadal 46 XY/fisiopatologia , Disgenesia Gonadal Mista/complicações , Disgenesia Gonadal Mista/fisiopatologia , Gonadotropinas/sangue , Humanos , Cariotipagem , Masculino , Oligospermia/genética , Oligospermia/fisiopatologia , Fenótipo , Puberdade , Estudos Retrospectivos , Índice de Gravidade de Doença , Espermatogênese/genética , Testículo/anormalidades , Testículo/metabolismo , Testosterona/sangue
14.
Am J Med Genet A ; 143A(21): 2616-22, 2007 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-17935253

RESUMO

We report on the follow-up of a set of monozygotic (MZ) twins who were concordant for peripheral blood karyotype 45,X/46,XY but discordant for phenotypic sex. One twin is a phenotypically normal male and the other twin has asymetrical gonadal dysgenesis. The female twin has the mos45,X/46,XY karyotype in all four tissues: left testis, right streak, vas deferens, and clitoral skin. The normal male twin has the normal 46,XY karyotype in all three tissues tested: foreskin, scrotal skin, and testis. Follow-up of the twins at age 21, revealed persistence of mos45,X/46,XY karyotype in peripheral blood into adult life. However, the male grew up with normal male stature, reaching an adult height of 182 cm. The female twin received low dose estrogen replacement with complete breast development at age 14 years. She reached an adult height of 156 cm. At 21 years of age the male twin had normal testicular endocrine function, but severe oligospermia. The long-term follow-up of this set of MZ twins indicate that the male twin has the mosaicism confined to peripheral blood and has the normal 46,XY male constitution. This was further confirmed by his normal male stature and normal testicular endocrine function. The 45X cell line is likely due to his receiving these cells passively from his twin sister via placental anastomoses in utero. The exposure to these 45,X cells during development may have had an impact on his spermatogenesis.


Assuntos
Doenças em Gêmeos , Disgenesia Gonadal Mista/genética , Gêmeos Monozigóticos , Adolescente , Adulto , Feminino , Seguimentos , Disgenesia Gonadal Mista/sangue , Humanos , Hibridização In Situ , Cariotipagem , Masculino , Repetições de Microssatélites , Mosaicismo , Fenótipo , Fatores de Tempo
15.
Fertil Steril ; 85(3): 706-13, 2006 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-16500342

RESUMO

OBJECTIVE: To characterize the phenotype, modes of inheritance, karyotype, and molecular basis of patients with idiopathic hypogonadotropic hypogonadism (IHH). DESIGN: Review of medical records, karyotyping, and collation of gene mutation analysis. SETTING: University molecular reproductive endocrinology laboratory. PATIENT(S): Patients with IHH. INTERVENTION(S): Review of medical records, laboratory studies, and molecular studies. MAIN OUTCOME MEASURE(S): Sense of smell, severity of IHH (complete vs. incomplete), associated anomalies, karyotype, mutation analysis, and genotype/phenotype correlations were studied. RESULT(S): Of 315 patients with IHH, 6.3% had one or more affected relatives. Autosomal recessive inheritance was likely in most of these familial cases, but autosomal-dominant and X-linked recessive inheritance patterns were likely in some families. Complete IHH was more commonly found in males (62%), whereas incomplete IHH was more commonly observed in females (54.3%). Anosmia was present in 31.3% of males and 27.9% of females. The karyotype was normal in all 19 females tested, but was abnormal in 3 of 57 (5.3%) of males tested. Although cryptorchidism did not differ among those who were anosmic vs. normosmic, it was approximately four times more common in patients with complete IHH than incomplete IHH (15.3% vs. 3.9%). Approximately 10% of the IHH patients tested had mutations in either the GNRHR or KAL1 gene. CONCLUSION(S): Idiopathic hypogonadotropic hypogonadism is a heterogeneous disorder affecting fertility, in which the number of familial cases is probably underestimated. Further study of genes that regulate hypothalamic-pituitary development and function will likely reveal important information regarding the development of normal puberty in humans.


Assuntos
Hipogonadismo/genética , Síndrome de Kallmann/genética , Adolescente , Criptorquidismo/genética , Proteínas da Matriz Extracelular/genética , Feminino , Humanos , Hipogonadismo/fisiopatologia , Incidência , Síndrome de Kallmann/epidemiologia , Cariotipagem , Masculino , Mutação , Proteínas do Tecido Nervoso/genética , Receptores LHRH/genética , Estudos Retrospectivos , Índice de Gravidade de Doença , Caracteres Sexuais , Distribuição por Sexo
16.
South Med J ; 99(8): 894-7, 2006 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-16929890

RESUMO

The diagnosis of granular acute lymphoblastic leukemia (ALL) can be problematic as the cytoplasmic granules found in many blast cells may mimic those seen in acute myelogenous leukemia (AML). This rare variant of B-cell ALL is more commonly diagnosed in children, but may occur in adults. We report a case of granular B-ALL in a 56-year-old female and review the literature.


Assuntos
Células da Medula Óssea/patologia , Grânulos Citoplasmáticos/patologia , Leucemia-Linfoma Linfoblástico de Células Precursoras/patologia , Biópsia , Diagnóstico Diferencial , Feminino , Citometria de Fluxo , Humanos , Pessoa de Meia-Idade
17.
J Cutan Pathol ; 29(10): 608-12, 2002 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-12453299

RESUMO

BACKGROUND: Extramedullary hematopoiesis is a well-documented manifestation of chronic myeloproliferative disorders, most commonly seen in chronic idiopathic myelofibrosis (agnogenic myeloid metaplasia), but rarely in chronic myelogenous leukemia. It typically occurs in the spleen and liver, but has also been described in skin. Microscopically, foci of extramedullary hematopoiesis consist of erythroid and myeloid precursors intermixed with megakaryocytes. The megakaryocytes may elaborate fibrogenic cytokines, which induce proliferation of fibroblasts. The term 'sclerosing extramedullary hematopoietic tumor' has been applied to this latter entity and its resemblance to a fibrohistiocytic neoplasm has been noted. METHODS: We report the case of a 66-year-old man, whose cutaneous sclerosing extramedullary hematopoietic tumor preceded the diagnosis of chronic myelogenous leukemia.


Assuntos
Hematopoese Extramedular , Leucemia Mielogênica Crônica BCR-ABL Positiva/patologia , Esclerose/patologia , Dermatopatias/patologia , Pele/patologia , Idoso , Biomarcadores Tumorais/metabolismo , Núcleo Celular/patologia , Células Gigantes/metabolismo , Células Gigantes/patologia , Hematopoese Extramedular/fisiologia , Humanos , Imuno-Histoquímica , Leucemia Mielogênica Crônica BCR-ABL Positiva/complicações , Leucemia Mielogênica Crônica BCR-ABL Positiva/metabolismo , Masculino , Esclerose/etiologia , Esclerose/metabolismo , Pele/metabolismo , Dermatopatias/etiologia , Dermatopatias/metabolismo , Fator de von Willebrand/metabolismo
18.
Am J Hum Genet ; 73(5): 1027-40, 2003 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-14526392

RESUMO

Chromosome 22, particularly band 22q11.2, is predisposed to rearrangements due to misalignments of low-copy repeats (LCRs). DiGeorge/velocardiofacial syndrome (DG/VCFS) is a common disorder resulting from microdeletion within the same band. Although both deletion and duplication are expected to occur in equal proportions as reciprocal events caused by LCR-mediated rearrangements, very few microduplications have been identified. We have identified 13 cases of microduplication 22q11.2, primarily by interphase fluorescence in situ hybridization (FISH). The size of the duplications, determined by FISH probes from bacterial artificial chromosomes and P(1) artificial chromosomes, range from 3-4 Mb to 6 Mb, and the exchange points seem to involve an LCR. Molecular analysis based on 15 short tandem repeats confirmed the size of the duplications and indicated that at least 1 of 15 loci has three alleles present. The patients' phenotypes ranged from mild to severe, sharing a tendency for velopharyngeal insufficiency with DG/VCFS but having other distinctive characteristics, as well. Although the present series of patients was ascertained because of some overlapping features with DG/VCF syndromes, the microduplication of 22q11.2 appears to be a new syndrome.


Assuntos
Anormalidades Múltiplas/genética , Anormalidades Múltiplas/fisiopatologia , Cromossomos Humanos Par 22/genética , Análise Citogenética , Duplicação Gênica , Anormalidades Múltiplas/patologia , Adolescente , Criança , Pré-Escolar , Bandeamento Cromossômico , Deleção Cromossômica , Feminino , Genótipo , Humanos , Hibridização in Situ Fluorescente , Lactente , Recém-Nascido , Interfase , Masculino , Repetições de Microssatélites/genética , Fenótipo , Polimorfismo Genético/genética , Síndrome
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