RESUMO
A C4 DNA polymorphism that can subdivide C4 allotypes and major histocompatibility complex-linked complement gene cluster allele combinations (complotypes) that are not distinguishable by standard electrophoretic means was used to assess further the distribution and linkage association of C4 variants. Segregation of the DNA polymorphism in family studies allowed assignment of particular variants to particular major histocompatibility complex haplotypes. These studies revealed that some complotypes were exclusively correlated with a particular C4 DNA variant, whereas others were not and could be subdivided according to which particular C4 DNA variant was observed. When complotypes that could be subdivided at the DNA level were considered in relation to flanking major histocompatibility complex markers, it was apparent that complotypes associated with major histocompatibility complex "extended haplotypes" had an exclusive correlation with a particular C4 DNA variant. This finding supports the hypothesis that "extended haplotypes" are unique associations of major histocompatibility complex allele combinations and are genetically similar, stably inherited units.
Assuntos
Complemento C4/genética , Antígenos HLA/genética , Antígenos HLA-D/genética , Antígenos HLA-DR/genética , Alelos , Boston , Ligação Genética , Antígenos HLA-B , Haplótipos , Humanos , Técnicas In Vitro , Minnesota , Polimorfismo Genético , População BrancaRESUMO
A young woman with features resembling de Lange syndrome had a normal banded karyotype. Similar phenotypes were present in a maternal aunt and uncle. Utilizing high-resolution banding, the propositus was found to have a chromosomal abnormality characterized by dup(4p)del(9p). Using the same banding technique, her mother and two of her siblings were identified as having balanced reciprocal translocations. Chromosome studies with high-resolution banding should be performed in these instances even in the presence of a normal banded karyotype. Determining a chromosomal basis for the phenotype may lead to a significant reproductive risk in individuals with balanced chromosomal rearrangements and may afford them with the opportunity to pursue prenatal diagnosis.
Assuntos
Aberrações Cromossômicas/genética , Cromossomos Humanos 6-12 e X , Síndrome de Cornélia de Lange/genética , Deficiência Intelectual/genética , Adolescente , Adulto , Pré-Escolar , Bandeamento Cromossômico , Transtornos Cromossômicos , Feminino , Aconselhamento Genético , Humanos , Cariotipagem , Masculino , LinhagemAssuntos
Hiperplasia Suprarrenal Congênita/genética , Complexo Principal de Histocompatibilidade , Esteroide Hidroxilases/deficiência , Complemento C2/genética , Complemento C4/genética , Fator B do Complemento/genética , Feminino , Marcadores Genéticos , Teste de Histocompatibilidade , Humanos , Lactoilglutationa Liase/genética , Escore Lod , Masculino , Sódio/metabolismoRESUMO
The fragile-X syndrome, an X-linked form of mental retardation, is estimated to affect one in every 1,000 to 2,000 live-born male infants. Most commonly, fragile-X syndrome has been detected only after patients clearly demonstrate developmental delay, and frequently detection occurs only if the family history is consistent with X-linked mental retardation. Macro-orchidism is a finding commonly associated with the fragile-X syndrome. It has been suggested that the sparsity of reports of macro-orchidism among prepubertal boys with the fragile-X syndrome might be due to lack of careful measurement of the tests rather than to initiation of the enlargement at puberty. A 5-month-old infant with fragile-X syndrome, ascertained through testicular enlargement noted by actual measurement of testicular size as part of his physical examination, is reported.
Assuntos
Síndrome do Cromossomo X Frágil/diagnóstico , Aberrações dos Cromossomos Sexuais/diagnóstico , Testículo/patologia , Adulto , Desenvolvimento Infantil , Citodiagnóstico , Feminino , Humanos , Lactente , Deficiência Intelectual/genética , MasculinoRESUMO
Polymorphisms of the proteins encoded by genes that lie within the major histocompatibility complex (MHC) have served as useful markers for organ transplantation and in genetic analysis of a large number of MHC-linked diseases. To extend the range of MHC polymorphic markers, we used a complementary-DNA probe specific for the fourth component of human complement (C4) to identify a new variant within the MHC. Polymorphic variants at the DNA level were detected among subjects with identical phenotypes of the corresponding protein. C4 genomic polymorphisms are inherited with the segment of the short arm of chromosome 6 that carries the HLA-DR and complement loci. The autosomal codominant mode of inheritance of this genetic marker and its utility for evaluation of 21-hydroxylase-deficiency congenital adrenal hyperplasia, one of the many MHC-linked diseases, were established.
Assuntos
Complemento C4/genética , DNA/genética , Marcadores Genéticos , Complexo Principal de Histocompatibilidade , Polimorfismo Genético , Hiperplasia Suprarrenal Congênita/genética , Cromossomos Humanos 6-12 e X , Ligação Genética , Variação Genética , HumanosRESUMO
Anthropometric methods were used to examine 18 males 18 to 69 years old with the Fragile-X syndrome. Thirteen of 15 subjects had macroorchidism. The average height of the individuals with the Fragile-X was less than that of published standards. Seventeen of the 18 subjects had absolute or relative macrocephaly, and two-thirds of the subjects were dolichocephalic. For the group as a whole, facial and ear lengths were increased, and facial breadth, hand length, and foot length were decreased. It is suggested that relationships between various measurements of an individual may be more important than any single measurements for conveying the characteristic appearance of an individual with the Fragile-X syndrome.
Assuntos
Antropometria , Síndrome do Cromossomo X Frágil/patologia , Deficiência Intelectual/patologia , Aberrações dos Cromossomos Sexuais/patologia , Adolescente , Adulto , Idoso , Estatura , Cefalometria , Pé/anatomia & histologia , Mãos/anatomia & histologia , Humanos , Masculino , Pessoa de Meia-Idade , Testículo/anormalidadesRESUMO
A number of patients with retinoblastoma have a deletion of chromosome 13. Comparison of the deleted segments from different individuals reveals that all deletions involve chromosome band 13q14. This observation has lead to the hypothesis that in this region is a gene of genes important in the etiology of retinoblastoma. As a first step toward understanding those genes, the authors successfully isolated five DNA fragments from chromosome 13 using recombinant DNA techniques. The DNA fragments from chromosome 13 will be useful in identifying DNA polymorphic sites that are linked to the retinoblastoma locus tentatively assigned to 13q14. Such DNA polymorphisms will be important in the genetic counselling of families with retinoblastoma. These chromosome 13q14 fragments also may be useful in searching for microdeletions of 13q14.
Assuntos
Cromossomos Humanos 13-15 , DNA de Neoplasias/isolamento & purificação , Neoplasias Oculares/genética , Retinoblastoma/genética , Animais , Autorradiografia , Deleção Cromossômica , Mapeamento Cromossômico , Clonagem Molecular/métodos , Cricetinae , Enzimas de Restrição do DNA/genética , DNA Recombinante/isolamento & purificação , Humanos , Células Híbridas , Cariotipagem , Camundongos , Polimorfismo Genético , RoedoresRESUMO
HLA, complement, and glyoxalase I alleles were studied in 29 families in which at least one member has classical 21-hydroxylase-deficiency congenital adrenal hyperplasia. A rare complement allele, C4B*31, was found in over 20% of the haplotypes defined in these families and was always part of the complement haplotype BF*F, C2*C, C4A*Q0, C4B*31 (abbreviated FCO,31). The haplotype containing this rare set of complement alleles always carried the rare HLA allele, HLA-Bw47, usually carried HLA-A3, and almost always had the alleles HLA-Cw6, HLA-DR7, and the glyoxalase I (GLO) allele GLO1. Thus over 20% of the haplotypes in the population studied contained all or almost all of the rare extended haplotype HLA-(A3), Bw47, Cw6,DR7, FCO,31, GLO 1. 3 other haplotypes were each found twice in unrelated patients concordant for their disease phenotype and ethnic background. Extended MHC haplotypes may be markers for different genetic mutations causing 21-hydroxylase deficiency.
Assuntos
Hiperplasia Suprarrenal Congênita/genética , Complexo Principal de Histocompatibilidade , Oxigenases de Função Mista/deficiência , Alelos , Cromossomos Humanos 6-12 e X , Etnicidade , Feminino , Frequência do Gene , Genes MHC da Classe II , Genótipo , Antígenos HLA/genética , Humanos , Lactoilglutationa Liase/genética , Masculino , Oxigenases de Função Mista/genéticaAssuntos
Aberrações Cromossômicas/diagnóstico , DNA Recombinante , Deficiência Intelectual/genética , Transtornos Cromossômicos , Fragilidade Cromossômica , Mapeamento Cromossômico , Cromossomos Humanos 13-15 , Feminino , Síndrome do Cromossomo X Frágil/diagnóstico , Heterozigoto , Humanos , Masculino , Biologia Molecular , Síndrome de Prader-Willi/genética , Testículo/anormalidades , Cromossomo XAssuntos
Testes Genéticos , Programas Médicos Regionais/organização & administração , Erros Inatos do Metabolismo dos Aminoácidos/genética , Hipotireoidismo Congênito , Síndrome do Cromossomo X Frágil/genética , Galactosemias/genética , Humanos , Hipotireoidismo/genética , Recém-Nascido , Deficiência Intelectual/genética , New EnglandRESUMO
Esterase D was quantitatively measured in the red blood cells from three patients from three separate kindreds who had abnormalities of chromosome 13. The esterase D activity was proportional to the number of copies of the q14 region of chromosome 13 present. These findings confirm published data localizing the esterase D gene to chromosome band 13q14, a region which is important in the etiology of retinoblastoma. Fifty-one additional retinoblastoma patients not known to have any chromosomal defect also underwent esterase D determination. In none of these patients did the esterase D measurement detect a 13q14 deletion. The normal esterase D levels in this series of 51 retinoblastoma patients suggest that deletion of an esterase D locus is infrequent in retinoblastoma patients. It must be noted that patients who are mosaics, with a 13q14 deletion in only a fraction of all somatic cells, could possibly have normal red blood cell esterase D levels. Further study is necessary to determine if esterase D determination of all retinoblastoma patients is a worthwhile clinical tool.
Assuntos
Carboxilesterase , Hidrolases de Éster Carboxílico/genética , Deleção Cromossômica , Cromossomos Humanos 13-15/ultraestrutura , Neoplasias Oculares/genética , Retinoblastoma/genética , Adolescente , Adulto , Hidrolases de Éster Carboxílico/sangue , Criança , Pré-Escolar , Neoplasias Oculares/enzimologia , Feminino , Humanos , Lactente , Isoenzimas/sangue , Isoenzimas/genética , Masculino , Pessoa de Meia-Idade , Retinoblastoma/enzimologia , TrissomiaAssuntos
Transtorno Autístico/genética , Síndrome do Cromossomo X Frágil/complicações , Aberrações dos Cromossomos Sexuais/complicações , Transtorno Autístico/etiologia , Criança , Síndrome do Cromossomo X Frágil/genética , Genes Recessivos , Humanos , Deficiência Intelectual/etiologia , Deficiência Intelectual/genética , MasculinoAssuntos
Doença de Hirschsprung/genética , Adulto , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Linhagem , Estenose Pilórica/genética , RiscoAssuntos
Cromossomos Humanos 6-12 e X , Mapeamento Cromossômico , Genes , Ligação Genética , HumanosRESUMO
Wilms tumor developed in five cousins in a family. Two with bilateral tumors have died, but three with unilateral lesions have survived. None of the patients had associated chromosome defects, aniridia, hemihypertrophy, or other anomalies. The pattern of Wilms tumor in the family is consistent with several postulated mechanisms of inheritance of the neoplasm, and shows that relatives within affected families may be at risk.