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1.
J Med Genet ; 41(9): 669-78, 2004 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-15342697

RESUMO

INTRODUCTION: Array comparative genomic hybridisation (array CGH) is a powerful method that detects alteration of gene copy number with greater resolution and efficiency than traditional methods. However, its ability to detect disease causing duplications in constitutional genomic DNA has not been shown. We developed an array CGH assay for X linked hypopituitarism, which is associated with duplication of Xq26-q27. METHODS: We generated custom BAC/PAC arrays that spanned the 7.3 Mb critical region at Xq26.1-q27.3, and used them to search for duplications in three previously uncharacterised families with X linked hypopituitarism. RESULTS: Validation experiments clearly identified Xq26-q27 duplications that we had previously mapped by fluorescence in situ hybridisation. Array CGH analysis of novel XH families identified three different Xq26-q27 duplications, which together refine the critical region to a 3.9 Mb interval at Xq27.2-q27.3. Expression analysis of six orthologous mouse genes from this region revealed that the transcription factor Sox3 is expressed at 11.5 and 12.5 days after conception in the infundibulum of the developing pituitary and the presumptive hypothalamus. DISCUSSION: Array CGH is a robust and sensitive method for identifying X chromosome duplications. The existence of different, overlapping Xq duplications in five kindreds indicates that X linked hypopituitarism is caused by increased gene dosage. Interestingly, all X linked hypopituitarism duplications contain SOX3. As mutation of this gene in human beings and mice results in hypopituitarism, we hypothesise that increased dosage of Sox3 causes perturbation of pituitary and hypothalamic development and may be the causative mechanism for X linked hypopituitarism.


Assuntos
Cromossomos Humanos X/genética , Proteínas de Ligação a DNA/genética , Duplicação Gênica , Genes Duplicados/genética , Doenças Genéticas Ligadas ao Cromossomo X/genética , Proteínas de Grupo de Alta Mobilidade/genética , Hipopituitarismo/genética , Fatores de Transcrição/genética , Adolescente , Adulto , Animais , Criança , Pré-Escolar , Feminino , Regulação da Expressão Gênica no Desenvolvimento , Ligação Genética/genética , Genoma Humano , Humanos , Hipotálamo/embriologia , Hipotálamo/metabolismo , Hibridização in Situ Fluorescente , Lactente , Recém-Nascido , Masculino , Camundongos , Hibridização de Ácido Nucleico , Linhagem , Hipófise/embriologia , Hipófise/metabolismo , Reprodutibilidade dos Testes , Fatores de Transcrição SOXB1
2.
Cleft Palate Craniofac J ; 39(2): 233-45, 2002 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-11879083

RESUMO

The Proteus syndrome is a rare congenital hamartomatous condition that is characterized by a wide range of malformations, sometimes involving the face. Common manifestations include partial gigantism, congenital lipomas, and plantar hyperplasia. In this report we describe the craniofacial clinicopathological development in a girl with Proteus syndrome from age 6 to 20 years. The patient had pronounced hemifacial hypertrophy, exostoses in the left parietal region, and enlargement of the inferior alveolar nerve and mandibular canal in the affected region. The dental development of the affected left mandible and maxilla was characterized by extremely premature development and eruption of the primary and permanent teeth and by pronounced idiopathic root resorptions. The multidisciplinary management of the patient and the treatment outcome is reported. A review of the Proteus patients in the literature who exhibited manifestation in the craniofacial region is presented.


Assuntos
Doenças Ósseas/etiologia , Ossos Faciais/patologia , Síndrome de Proteu/complicações , Doenças Dentárias/etiologia , Adolescente , Adulto , Cefalometria , Criança , Exostose/etiologia , Assimetria Facial/etiologia , Feminino , Seguimentos , Humanos , Hipertrofia , Mandíbula/patologia , Nervo Mandibular/patologia , Odontogênese/fisiologia , Ortodontia Corretiva , Osteotomia de Le Fort , Osso Parietal/patologia , Radiografia Panorâmica , Reabsorção da Raiz/etiologia , Erupção Dentária/fisiologia , Resultado do Tratamento
3.
J Clin Endocrinol Metab ; 85(11): 4354-8, 2000 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-11095479

RESUMO

Splenomegaly with sea-blue histiocytes is not associated with dyslipidemia, except in severe cases of hypertriglyceridemia, Tangier disease, or lecithin cholesterol acyltransferase deficiency. We describe two kindreds in which the sea-blue histiocyte syndrome was associated with an apoE variant in the absence of severe dyslipidemia. Both patients presented with mild hypertriglyceridemia and splenomegaly. After splenectomy both patients developed severe hypertriglyceridemia. Pathological evaluation of the spleen revealed the presence of sea-blue histiocytes. A mutation of apoE was demonstrated, with a 3-bp deletion resulting in the loss of a leucine at position 149 in the receptor-binding region of the apoE molecule [apoE (delta149 Leu)]. Although both probands were unrelated, they were of French Canadian ancestry, suggesting the possibility of a founder effect. In summary, we describe two unrelated probands with primary sea-blue histiocytosis who had normal or mildly elevated serum triglyceride concentrations that markedly increased after splenectomy. In addition, we provide evidence linking the syndrome to an inherited dominant mutation in the apoE gene, a 3-bp deletion on the background of an apoE 3 allele that causes a derangement in lipid metabolism and leads to splenomegaly in the absence of severe hypertriglyceridemia.


Assuntos
Apolipoproteínas E/genética , Hipertrigliceridemia/complicações , Lipoproteínas/sangue , Deleção de Sequência , Baço/patologia , Esplenomegalia/genética , Adulto , Alanina Transaminase/sangue , Animais , Sítios de Ligação , Éxons , Humanos , Hipertrigliceridemia/genética , Leucina , Proteína-1 Relacionada a Receptor de Lipoproteína de Baixa Densidade , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias , Coelhos , Receptores de Lipoproteínas/metabolismo , Esplenectomia , Esplenomegalia/patologia , Esplenomegalia/cirurgia , Triglicerídeos/sangue
4.
Genomics ; 69(2): 174-81, 2000 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-11031100

RESUMO

We investigated a family with a duplication, dup(X)q26-q27, that was present in two brothers, their mother, and their maternal grandmother. The brothers carrying the duplication displayed spina bifida and panhypopituitarism, whereas a third healthy brother inherited the normal X chromosome. Preferential inactivation of the X chromosome containing the duplication was evident in healthy carrier females. We determined the boundaries of the Xq26-q27 duplication. Via interphase FISH analysis we narrowed down each of the two breakpoint regions to approximately 300-kb intervals. The proximal breakpoint is located in Xq26.1 between DXS1114 and HPRT and is contained in YAC yWXD599, while the distal breakpoint is located in Xq27.3 between DXS369 and DXS1200 and contained in YAC yWXD758. The duplication comprises about 13 Mb. Evidence from the literature points to a predisposing gene for spina bifida in Xq27. We hypothesize that the spina bifida in the two brothers may be due to interruption of a critical gene in the Xq27 breakpoint region. Several candidate genes were mapped to the Xq27 critical region but none was shown to be disrupted by the duplication event. Recently, M. Lagerström-Fermér et al. (1997, Am. J. Hum. Genet. 60, 910-916) reported on a family with X-linked recessive panhypopituitarism associated with a duplication in Xq26; however, no details were reported on the extent of the duplication. Our study corroborates their hypothesis that X-linked recessive panhypopituitarism is likely to be caused by a gene encoding a dosage-sensitive protein involved in pituitary development. We place the putative gene between DXS1114 and DXS1200, corresponding to the interval defined by the duplication in the present family.


Assuntos
Aberrações Cromossômicas , Hipopituitarismo/genética , Disrafismo Espinal/genética , Cromossomo X , Mapeamento Cromossômico , Cromossomos Artificiais de Levedura , Mecanismo Genético de Compensação de Dose , Etiquetas de Sequências Expressas , Feminino , Ordem dos Genes , Haplótipos/genética , Heterozigoto , Humanos , Masculino , Linhagem
5.
Mayo Clin Proc ; 75(3): 265-72, 2000 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-10725953

RESUMO

An autosomal dominant tumor predisposition syndrome, von Hippel-Lindau disease (VHL) is characterized by the presence of benign and malignant tumors. Hallmark lesions include retinal angiomas, hemangioblastomas of the cerebellum and spinal cord, and renal cell carcinomas. Affected persons may also have angiomatous or cystic lesions of the kidneys, pancreas, and epididymis, as well as adrenal pheochromocytomas. In this article, we discuss the clinical features and diagnostic criteria for this clinically underdiagnosed condition. An update on recent findings regarding the molecular genetics of VHL is provided, including a discussion of the evolving understanding of genotype-phenotype correlations. Understanding the molecular and functional aspects of this condition will lead to the development of strategies for the management and treatment of inherited and sporadic VHL-associated tumors.


Assuntos
Ligases , Proteínas Supressoras de Tumor , Ubiquitina-Proteína Ligases , Doença de von Hippel-Lindau/diagnóstico , Doença de von Hippel-Lindau/genética , Neoplasias das Glândulas Suprarrenais/diagnóstico , Neoplasias das Glândulas Suprarrenais/genética , Neoplasias do Sistema Nervoso Central/diagnóstico , Neoplasias do Sistema Nervoso Central/genética , Diagnóstico Diferencial , Genes Supressores de Tumor , Testes Genéticos , Genótipo , Hemangioblastoma/diagnóstico , Hemangioblastoma/genética , Hemangioma/diagnóstico , Hemangioma/genética , Humanos , Neoplasias Renais/diagnóstico , Neoplasias Renais/genética , Biologia Molecular , Neovascularização Patológica , Fenótipo , Feocromocitoma/diagnóstico , Feocromocitoma/genética , Proteínas/genética , Neoplasias da Retina/diagnóstico , Neoplasias da Retina/genética , Proteína Supressora de Tumor Von Hippel-Lindau
6.
J Clin Invest ; 105(2): 191-8, 2000 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-10642597

RESUMO

Congenital disorders of glycosylation (CDGs) are metabolic deficiencies in glycoprotein biosynthesis that usually cause severe mental and psychomotor retardation. Different forms of CDGs can be recognized by altered isoelectric focusing (IEF) patterns of serum transferrin (Tf). Two patients with these symptoms and similar abnormal Tf IEF patterns were analyzed by metabolic labeling of fibroblasts with ¿2-(3)Hmannose. The patients produced a truncated dolichol-linked precursor oligosaccharide with 5 mannose residues, instead of the normal precursor with 9 mannose residues. Addition of 250 microM mannose to the culture medium corrected the size of the truncated oligosaccharide. Microsomes from fibroblasts of these patients were approximately 95% deficient in dolichol-phosphate-mannose (Dol-P-Man) synthase activity, with an apparent K(m) for GDP-Man approximately 6-fold higher than normal. DPM1, the gene coding for the catalytic subunit of Dol-P-Man synthase, was altered in both patients. One patient had a point mutation, C(274)G, causing an R(92)G change in the coding sequence. The other patient also had the C(274)G mutation and a 13-bp deletion that presumably resulted in an unstable transcript. Defects in DPM1 define a new glycosylation disorder, CDG-Ie.


Assuntos
Defeitos Congênitos da Glicosilação/enzimologia , Defeitos Congênitos da Glicosilação/genética , Manosiltransferases/deficiência , Manosiltransferases/genética , Mutação , Encefalopatias Metabólicas Congênitas/diagnóstico , Encefalopatias Metabólicas Congênitas/enzimologia , Encefalopatias Metabólicas Congênitas/etiologia , Sequência de Carboidratos , Células Cultivadas , Defeitos Congênitos da Glicosilação/complicações , Defeitos Congênitos da Glicosilação/diagnóstico , Análise Mutacional de DNA , Deficiências do Desenvolvimento/diagnóstico , Feminino , Fibroblastos/citologia , Fibroblastos/enzimologia , Glicosídeo Hidrolases/metabolismo , Glicosilação , Humanos , Lactente , Focalização Isoelétrica , Isoenzimas/deficiência , Isoenzimas/genética , Isoenzimas/metabolismo , Masculino , Manose/metabolismo , Manosiltransferases/metabolismo , Microcefalia/diagnóstico , Dados de Sequência Molecular , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Convulsões/diagnóstico , Deleção de Sequência , Transferrina/metabolismo
7.
Cancer Epidemiol Biomarkers Prev ; 8(8): 715-9, 1999 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-10744132

RESUMO

Carcinoid tumors are generally thought to be sporadic, except for a small proportion that occur as a part of multiple endocrine neoplasia syndromes. Data regarding the familial occurrence of carcinoid as well as its potential association with other neoplasms are limited. A chart review was conducted on patients indexed for malignant carcinoid tumor of the gastrointestinal tract seen at the Mayo Clinic between 1988 and 1996. A survey of family history of malignancies and personal history of other tumors was mailed to all eligible patients. Data for 245 patients were analyzed. Observed rates of carcinoids and other malignancies were compared with Surveillance, Epidemiology, and End Results data. Estimates of the cumulative probability for first-degree relatives developing a carcinoid tumor were calculated. Nine (3.7%) patients with carcinoid tumor had at least one first-degree relative with the same malignancy. The rate of carcinoid tumor in first-degree relatives of probands was higher (P < 0.0001) than expected based on the Surveillance, Epidemiology, and End Results population data. Cumulative probability in a first-degree relative for developing a carcinoid was calculated to be 1.5% at age 80. There was an increased risk for developing a carcinoid tumor among first-degree relatives of patients with carcinoid. Neither patients with carcinoid nor their first-degree relatives had an increased incidence of other malignancies.


Assuntos
Tumor Carcinoide/genética , Neoplasias Gastrointestinais/genética , Adolescente , Adulto , Idoso , Tumor Carcinoide/complicações , Saúde da Família , Feminino , Neoplasias Gastrointestinais/epidemiologia , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Linhagem , Medição de Risco
8.
Mayo Clin Proc ; 73(11): 1071-6, 1998 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-9818041

RESUMO

Neurofibromatosis (NF) type 1 (NF-1) is one of the most common of the neurocutaneous conditions, whereas NF type 2 (NF-2) accounts for an extremely small percentage of the total cases of NF. Indeed, most physicians will probably encounter at least one or two patients with NF-1 during the course of their practice. The manifestations can be varied and subtle; thus, the condition can sometimes be difficult to recognize. Nonetheless, the diagnosis of NF-1 is often clinically possible by the time the person is 10 years old. In this article, the diagnostic criteria for the most common types of NF are discussed, the common and some of the serious manifestations of both NF-1 and NF-2 are described, and suggestions for follow-up care are offered. Of importance, physicians must recognize that, although NF-1 and NF-2 share a common name, they are due to mutations in two different genes. Cure is not yet possible; thus, treatment is primarily symptomatic. A multi-disciplinary treatment team is often helpful, particularly for patients with complicated problems.


Assuntos
Neurofibromatoses , Cromossomos Humanos Par 17/genética , Cromossomos Humanos Par 22/genética , Testes Genéticos , Humanos , Neoplasias/genética , Neurofibromatoses/complicações , Neurofibromatoses/diagnóstico , Neurofibromatoses/genética , Neurofibromatoses/terapia , Neurofibromatose 1 , Neurofibromatose 2
9.
Am J Hum Genet ; 63(1): 125-34, 1998 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-9634525

RESUMO

Nijmegen breakage syndrome (NBS) is a rare autosomal recessive disorder characterized by microcephaly, a birdlike face, growth retardation, immunodeficiency, lack of secondary sex characteristics in females, and increased incidence of lymphoid cancers. NBS cells display a phenotype similar to that of cells from ataxia-telangiectasia patients, including chromosomal instability, radiation sensitivity, and aberrant cell-cycle-checkpoint control following exposure to ionizing radiation. A recent study reported genetic linkage of NBS to human chromosome 8q21, with strong linkage disequilibrium detected at marker D8S1811 in eastern European NBS families. We collected a geographically diverse group of NBS families and tested them for linkage, using an expanded panel of markers at 8q21. In this article, we report linkage of NBS to 8q21 in 6/7 of these families, with a maximum LOD score of 3.58. Significant linkage disequilibrium was detected for 8/13 markers tested in the 8q21 region, including D8S1811. In order to further localize the gene for NBS, we generated a radiation-hybrid map of markers at 8q21 and constructed haplotypes based on this map. Examination of disease haplotypes segregating in 11 NBS pedigrees revealed recombination events that place the NBS gene between D8S1757 and D8S270. A common founder haplotype was present on 15/18 disease chromosomes from 9/11 NBS families. Inferred (ancestral) recombination events involving this common haplotype suggest that NBS can be localized further, to an interval flanked by markers D8S273 and D8S88.


Assuntos
Quebra Cromossômica/genética , Cromossomos Humanos Par 8/genética , Mapeamento Cromossômico , Feminino , Efeito Fundador , Genes Recessivos/genética , Ligação Genética/genética , Genótipo , Haplótipos , Humanos , Desequilíbrio de Ligação/genética , Escore Lod , Masculino , Repetições de Microssatélites/genética , Linhagem , Recombinação Genética/genética
10.
Mayo Clin Proc ; 71(12): 1192-5, 1996 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-8945494

RESUMO

DNA testing has become relatively common during the past few years. All humans have an estimated five to eight mutated genes and are at risk for a genetic disorder. Recognition of these facts and development of DNA technology have created substantial interest in DNA testing as a diagnostic and management tool. As with any emerging technology, the applications and limitations must be understood in order to use the new tests wisely. In this review, the basic molecular diagnostic techniques are discussed. In addition, the emerging ethical debate surrounding the use of this new technology is summarized. Caution is necessary when DNA tests are being used, especially in presymptomatic situations.


Assuntos
DNA/análise , Genes/genética , Doenças Genéticas Inatas/diagnóstico , Doenças Genéticas Inatas/genética , Confidencialidade , Doenças Genéticas Inatas/psicologia , Ligação Genética , Humanos , Mutação , Reação em Cadeia da Polimerase , Valor Preditivo dos Testes
11.
Am J Med Genet ; 63(4): 525-8, 1996 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-8826429

RESUMO

Tracheoesophageal fistula (TEF) may occur as an isolated malformation or together with other malformations. To determine the recurrence risk of TEF or associated malformations in children and sibs, and to determine the frequency of associated malformations in index patients, we reviewed the Mayo Clinic records of 204 patients with TEF. Also, questionnaires were sent to patients or relatives. Questions were designed to determine whether the patient and relatives had TEF and/or related organ system (including VACTERL) malformations. The VACTERL association is a disorder characterized by 3 or more of the following: vertebral, anal, cardiac, renal, or radial anomalies, and TEF. One hundred twenty-eight families returned a completed questionnaire, and 140 index patients were ascertained based on complete medical records, questionnaire, and/or autopsy. Forty-one (29.3%) of 140 index patients had TEF with one other VACTERL malformation, and twenty-four (17.1%) of 140 index patients had TEF with at least two other VACTERL malformations. Of the 347 sibs of index patients, 5 (1.4%) had one VACTERL malformation each, including 1 sib with esophageal atresia (EA) without TEF. Of the 41 children of index patients, 1 (2.4%) had TEF plus two other VACTERL malformations; another had one non-TEF VACTERL malformation. From our study, the largest reported population of TEF patients to date, we conclude that: 1) nearly half (46%) of patients with tracheoesophageal fistula will exhibit other VACTERL malformations; 2) the recurrence risk for individuals with TEF to have affected children is 2-3%; and 3) there is an increased risk to relatives of TEF patients to exhibit other VACTERL malformations.


Assuntos
Anormalidades Múltiplas/genética , Fístula Traqueoesofágica/epidemiologia , Fístula Traqueoesofágica/genética , Anormalidades Múltiplas/epidemiologia , Adolescente , Adulto , Criança , Feminino , Cardiopatias Congênitas/complicações , Cardiopatias Congênitas/epidemiologia , Cardiopatias Congênitas/genética , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Linhagem , Inquéritos e Questionários , Fístula Traqueoesofágica/complicações
14.
Am J Med Genet ; 58(2): 143-6, 1995 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-8533805

RESUMO

Whole chromosome uniparental disomy (UPD) for several different chromosomes has been described in individuals with phenotypes that encompass a broad range of abnormalities. We prospectively searched for UPD in 25 cytogenetically normal individuals who had one or more of the following features: nonsyndromic multiple congenital anomalies, short stature, mental retardation, or dysmorphic findings. Using highly polymorphic microsatellite repeats, biparental inheritance of at least one locus on every chromosome was found in every individual and uniparental inheritance was not detected at any locus. If UPD does exist in this clinical setting, its frequency is less than 13.7% (95% confidence interval). Our data indicate that additional studies will be required to determine the true incidence of UPD in this population.


Assuntos
Anormalidades Múltiplas/genética , Aberrações Cromossômicas , Deficiência Intelectual/genética , Impressão Genômica , Heterozigoto , Humanos , Estudos Prospectivos
15.
Clin Genet ; 44(4): 185-9, 1993 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-8261647

RESUMO

Trisomy 16 is the most common trisomy in spontaneous abortions and is usually, if not always, lethal in the nonmosaic state. We report a liveborn infant with trisomy 16 mosaicism first diagnosed by amniocentesis at 20 weeks gestation. At birth, the infant was growth retarded and mildly dysmorphic. At age 14 months she was developmentally normal and had facial asymmetry. Her length, weight and head circumference were normal. Pure trisomy 16 was found in cells from the placenta. A normal female karyotype was found in lymphocytes from the infant. Skin fibroblasts revealed a trisomy 16 karyotype in 6 of 30 cells. Molecular analysis showed maternal uniparental heterodisomy, indicating that the trisomic conceptus arose from a nondisjunction of maternal meiosis. Fibroblasts may be the tissue of choice for detection of low-level trisomy 16 mosaicism.


Assuntos
Aberrações Cromossômicas , Cromossomos Humanos Par 16 , Trissomia , Amniocentese , DNA/análise , Feminino , Humanos , Recém-Nascido , Mosaicismo
16.
Mayo Clin Proc ; 67(7): 658-62, 1992 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-1434900

RESUMO

By identifying structural chromosome anomalies, the clinical cytogenetics laboratory can play a critical role in the diagnosis and treatment of patients with birth defects. Although many new staining techniques have been developed throughout the years to aid in the detection of anomalous chromosomes, some abnormalities still pose a special challenge to cytogeneticists. This difficulty is especially evident in patients with an abnormal chromosome that does not produce a recognizable banding pattern by conventional staining techniques. We describe a recently discovered method of identifying chromosomes by using whole chromosome-specific DNA probes and fluorescent in situ hybridization and provide examples of how this new procedure facilitated the identification of chromosome abnormalities in two patients with multiple birth defects.


Assuntos
Anormalidades Congênitas/genética , Hibridização In Situ/métodos , Deficiência Intelectual/genética , Translocação Genética , Adulto , Cromatina , Cromossomos Humanos Par 12 , Cromossomos Humanos Par 18 , Cromossomos Humanos Par 5 , Cromossomos Humanos Par 9 , Sondas de DNA , Feminino , Corantes Fluorescentes , Humanos , Recém-Nascido , Masculino
17.
Minn Med ; 75(5): 35-7, 1992 May.
Artigo em Inglês | MEDLINE | ID: mdl-1593995

RESUMO

Recent advances in genetics directly affect family physicians. Many diagnostic tests are currently available to screen the fetus for malformations and genetic diseases, and gene therapy is slowly becoming a reality. This article discusses some of the screening techniques available, including chromosome analysis, ultrasound, and DNA studies.


Assuntos
Genética Médica/tendências , Sondas de DNA , Feminino , Testes Genéticos/tendências , Terapia Genética/tendências , Humanos , Recém-Nascido , Papel do Médico , Gravidez , Diagnóstico Pré-Natal/tendências
18.
Am J Med Genet ; 42(5): 706-13, 1992 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-1632443

RESUMO

We report on 2 male propositi, their mothers, and a maternal aunt with a new skeletal dysplasia associated with a unique pattern of digital malformation, variable mild short stature, and mild bowleg with proximal overgrowth of the fibula. The digital malformations comprise a pattern of brachydactyly which includes short, abducted thumbs, short index fingers, and markedly short, abducted great toes. The radiographic findings include hypoplastic thumbs and great toes with short first metacarpals and first metatarsals, absent distal phalanges of the index fingers and second toes, and coalescence of the carpal and tarsal bones. Radiographs of the long bones show mild metaphyseal and epiphyseal irregularity, tibial spurs, and relative elongation of the fibulae. The males are very similarly affected whereas the females show phenotypic variation and are generally less severely affected. The family histories from 2 fairly extensive pedigrees suggest X-linked dominant inheritance.


Assuntos
Doenças do Desenvolvimento Ósseo/genética , Dedos/anormalidades , Genes Dominantes/genética , Ligação Genética , Dedos do Pé/anormalidades , Cromossomo X , Adolescente , Adulto , Doenças do Desenvolvimento Ósseo/diagnóstico por imagem , Criança , Feminino , Dedos/diagnóstico por imagem , Humanos , Masculino , Linhagem , Radiografia , Dedos do Pé/diagnóstico por imagem
19.
Cancer Genet Cytogenet ; 59(1): 12-9, 1992 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-1313329

RESUMO

Consistent cytogenetic abnormalities have been described in many pediatric solid tumors, including Ewing's sarcoma, Wilms' tumor, and neuroblastoma. Similar analysis of pediatric central nervous system (CNS) tumors has been hampered by technical problems. We report chromosome results from 39 pediatric CNS tumors. Abnormalities of chromosome 17 were noted in 3 of 11 primitive neuroectodermal tumors (including i(17q) in 2 tumors), confirming data observed by other investigators. Cells from 2 of 11 primitive neuroectodermal tumors (PNET) exhibited loss or structural abnormalities involving chromosome 11. Loss or distal deletion of chromosome 7q was noted in cells from two PNETs. Because other investigators have shown loss of heterozygosity on 17p in about one-third of PNET, we propose that chromosome regions 7q and 11 are areas worthy of further study in pediatric PNET. Numerical abnormalities were noted in 6 of 21 astrocytomas. Hyperdiploidy was demonstrated in 1 of 4 pilocytic astrocytomas and pseudopolyploidy was demonstrated in 4 of 13 anaplastic astrocytomas. Structural chromosome abnormalities (translocations, deletions) were noted in 4 of 13 anaplastic astrocytomas. Complex structural anomalies were observed in one craniopharyngioma. A rhabdoid tumor of the brain exhibited multiple complex structural rearrangements but did not exhibit the monosomy 22 observed in some rhabdoid tumors. Hypodiploidy and loss of chromosome 22 were noted in a clinically aggressive meningioma, corroborating observations by other investigators.


Assuntos
Astrocitoma/genética , Neoplasias Encefálicas/genética , Aberrações Cromossômicas , Transtornos Cromossômicos , Craniofaringioma/genética , Neoplasias Embrionárias de Células Germinativas/genética , Neoplasias Hipofisárias/genética , Astrocitoma/patologia , Neoplasias Encefálicas/patologia , Criança , Deleção Cromossômica , Cromossomos Humanos Par 11 , Cromossomos Humanos Par 17 , Cromossomos Humanos Par 22 , Craniofaringioma/patologia , Citogenética , Humanos , Cariotipagem , Neoplasias Embrionárias de Células Germinativas/patologia , Neoplasias Hipofisárias/patologia , Células Tumorais Cultivadas
20.
Circulation ; 85(1): 188-95, 1992 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-1728449

RESUMO

BACKGROUND: Maroteaux-Lamy syndrome is a lysosomal storage disease of mucopolysaccharide metabolism (MPS type VI) that may involve the mitral and aortic valves. Affected patients have other skeletal and oropharyngeal malformations that complicate anesthetic and surgical management. METHODS AND RESULTS: The present report describes the clinical, echocardiographic, and pathological findings in four patients with Maroteaux-Lamy syndrome. Two of three siblings underwent successful double-valve replacement for aortic and mitral valve stenoses. The third sibling, whose aortic and mitral valves were thick and fibrotic, died from septicemia after hip surgery. A fourth, unrelated patient also had successful double-valve replacement. CONCLUSIONS: Our experience emphasizes the potential difficulties in preoperative assessment and surgical treatment as well as the unique problems related to airway management in patients with this syndrome.


Assuntos
Estenose da Valva Aórtica/etiologia , Estenose da Valva Mitral/etiologia , Mucopolissacaridose VI/complicações , Adulto , Estenose da Valva Aórtica/diagnóstico por imagem , Estenose da Valva Aórtica/patologia , Ecocardiografia , Ecocardiografia Doppler , Feminino , Próteses Valvulares Cardíacas , Humanos , Masculino , Estenose da Valva Mitral/diagnóstico por imagem , Estenose da Valva Mitral/patologia , Mucopolissacaridose VI/diagnóstico por imagem , Mucopolissacaridose VI/patologia
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