RESUMO
Nonsyndromic hearing impairment is one of the most heterogeneous hereditary conditions, with more than 40 loci mapped on the human genome, however, only a limited number of genes implicated in hearing loss have been identified. We previously reported linkage to chromosome 7p15 for autosomal dominant hearing impairment segregating in an extended Dutch family (DFNA5). Here, we report a further refinement of the DFNA5 candidate region and the isolation of a gene from this region that is expressed in the cochlea. In intron 7 of this gene, we identified an insertion/deletion mutation that does not affect intron-exon boundaries, but deletes five G-triplets at the 3' end of the intron. The mutation co-segregated with deafness in the family and causes skipping of exon 8, resulting in premature termination of the open reading frame. As no physiological function could be assigned, the gene was designated DFNA5.
Assuntos
Proteínas de Transporte/genética , Perda Auditiva de Alta Frequência/genética , Mutação , Adolescente , Sequência de Aminoácidos , Animais , Criança , Pré-Escolar , Mapeamento Cromossômico , Feminino , Ligação Genética , Perda Auditiva de Alta Frequência/fisiopatologia , Humanos , Masculino , Camundongos , Dados de Sequência Molecular , Fases de Leitura Aberta , Linhagem , Presbiacusia/genética , Presbiacusia/fisiopatologia , Receptores de Estrogênio/química , Receptores de Estrogênio/genética , Alinhamento de SequênciaRESUMO
We report the prenatal diagnosis of a karyotype 46,XY,rec(6)dup p, inv(6) (p23q27) mat detected by fluorescence in situ hybridization using chromosome 6pter and 6qter specific DNA markers. This partial duplication-deletion (6p12-->pter; 6q27-->qter) emanated from a balanced pericentric inversion 46,XX inv(6) (p23q27)pat present in the mother. The phenotypes of two relatives with the same unbalanced anomaly are described. This report illustrates the sensitivity and specificity of fluorescence in situ hybridization (FISH) and its benefit in rapid and unequivocal prenatal diagnosis of subtle chromosomal rearrangements.
Assuntos
Inversão Cromossômica , Cromossomos Humanos Par 6 , Monossomia , Diagnóstico Pré-Natal , Trissomia , Anormalidades Múltiplas/diagnóstico , Anormalidades Múltiplas/genética , Aborto Terapêutico , Aberrações Cromossômicas/diagnóstico , Aberrações Cromossômicas/genética , Transtornos Cromossômicos , Ossos Faciais/anormalidades , Feminino , Doenças Fetais/diagnóstico , Doenças Fetais/genética , Humanos , Hibridização in Situ Fluorescente , Recém-Nascido , Deficiência Intelectual/genética , Rim/anormalidades , Masculino , Mosaicismo , Linhagem , Gravidez , Primeiro Trimestre da Gravidez , Segundo Trimestre da Gravidez , Gravidez em Diabéticas , Crânio/anormalidadesRESUMO
Pancreatic and salivary isoenzymes of amylase were determined in serum from 70 subjects. Thin-layer gel/isoelectric focusing was used to separate the isoenzymes. Because other studies (J. Lab. Clin. Med. 90: 141-151, 1977) show that the major isoamylases have isoelectric points between 5.8 and 7.2, we focused the sera on polyacrylamide gel plates with a pH gradient from 5.5 to 8.5. The separated amylase fractions were made visible by direct incubation with a commercially available dye-starch polymer. Isoelectric focusing proved to be convenient, precise, and reproducible, and it can be used as a routine analysis to detect even slight changes in serum amylase distributions. We found that the isoamylase distribution is age dependent, whereas total amylase activity shows no correlation with age.
Assuntos
Amilases/sangue , Isoenzimas/sangue , alfa-Amilases/sangue , Doença Aguda , Adolescente , Adulto , Fatores Etários , Idoso , Criança , Pré-Escolar , Cromatografia em Camada Fina , Eletroforese em Gel de Poliacrilamida , Humanos , Concentração de Íons de Hidrogênio , Lactente , Focalização Isoelétrica , Pessoa de Meia-Idade , Suco Pancreático/enzimologia , Pancreatite/enzimologia , Parotidite/enzimologia , Saliva/enzimologiaRESUMO
Aneuploidy detection for chromosome 21 by fluorescence in situ hybridization (FISH) to interphase nuclei using a probe specific for the alphoid DNA sequences D21Z1/D13Z1 should be avoided. An extreme heteromorphism, resulting in misdiagnosis if interphase FISH is the only test employed, may be far more frequent (4/101) than expected.
Assuntos
Aneuploidia , Cromossomos Humanos Par 21 , Humanos , Hibridização in Situ Fluorescente , Interfase/genéticaRESUMO
X-linked liver glycogenosis (XLG) is a glycogen storage disorder resulting from deficient activity of phosphorylase kinase (PHK). PHK consists of four different subunits: alpha, beta, gamma, and delta. Several genes encoding PHK subunits have been cloned and localized, but only the muscle alpha-subunit (PHKA) gene has been assigned to the X chromosome, in the region Xq12----q13. However, we have previously excluded the muscle PHKA gene as a candidate gene for the XLG mutation, as linkage analysis indicated that the mutation responsible for XLG is located in Xp22 and not in Xq12----q13. We report here the chromosomal localization by in situ hybridization of a liver PHKA gene to the distal region of chromosome Xp. Strong hybridization signals were observed on the distal part of the short arm of a chromosome identified as the X chromosome by cohybridization with an X chromosome-specific centromeric probe. The localization of this gene in the same chromosomal region as the disease gene responsible for XLG suggests that the liver PHKA gene is a highly likely candidate gene for the XLG mutation.
Assuntos
Mapeamento Cromossômico , Fígado/enzimologia , Fosforilase Quinase/genética , Cromossomo X , Sondas de DNA , Fluorescência , Humanos , Microscopia de Fluorescência , Hibridização de Ácido NucleicoRESUMO
Prolyl oligopeptidase is a large monomeric proline specific serine endopeptidase, the activity of which correlates well with different stages of depression. We have subregionally mapped human lymphocytic prolyl oligopeptidase (PREP) by FISH using a cosmid probe. The probe mapped to the long arm of chromosome 6, and the signal clustered in band q22.