Assuntos
Neuropatias Hereditárias Sensoriais e Autônomas/genética , Peptídeos e Proteínas de Sinalização Intracelular/genética , Mutação , Proteínas Serina-Treonina Quinases/genética , Adulto , Idade de Início , Sequência de Bases , Criança , Análise Mutacional de DNA , Feminino , Humanos , Masculino , México , Pessoa de Meia-Idade , Antígenos de Histocompatibilidade Menor , Linhagem , Proteína Quinase 1 Deficiente de Lisina WNK , Adulto JovemRESUMO
BACKGROUND: Steroid sulphatase (STS) deficiency has been described in a diversity of ethnic populations. The phenotype of STS deficiency, X-linked ichthyosis (XLI), is a genodermatosis characterized by dark scaly skin. About 90% of patients with XLI have complete deletion of the entire STS gene and flanking sequences. The variable number tandem repeats, on either side of the STS gene, appear to play an important role in these interstitial deletions due to nonallelic homologous recombination (NAHR). It is difficult to establish if this NAHR occurs between two chromosomes, between sister chromatids or between the same chromatid. OBJECTIVES: To identify the parental origin of the affected X-chromosome in seven unrelated sporadic cases of XLI. METHODS: Amplification of the regions from DXS89 to DXS1134 (telomeric-centromeric) including the 5' and 3' ends of the STS gene was performed through polymerase chain reaction. GeneScan analysis was performed using the DXS987, DXS8051 and DXS1060 markers located on the short arm of the X-chromosome. Fluorescence in situ hybridization analysis was performed with a digoxigenin-labelled cDNA STS probe. RESULTS: STS gene deletion in patients with XLI involved the sequences DXS1139 and DXF22S1. In five families segregation analysis showed paternal transmission of the affected X-chromosome in the XLI carrier. It was not possible to determine the parental origin of the affected X-chromosome in two families. CONCLUSIONS: These data strongly suggest that STS gene deletion occurred in the male meiosis probably due to an intrachromosomal event, recombination between S232 sequences on the same DNA molecule, or during the process of DNA replication.
Assuntos
Cromossomos Humanos X , Doenças Genéticas Ligadas ao Cromossomo X/genética , Ligação Genética/genética , Ictiose Ligada ao Cromossomo X/genética , Transmissão Vertical de Doenças Infecciosas/prevenção & controle , Feminino , Deleção de Genes , Humanos , Masculino , Recombinação GenéticaRESUMO
BACKGROUND: X-linked ichthyosis (XLI), an inborn error of metabolism, is due to steroid sulphatase (STS) deficiency. Most patients with XLI harbour complete deletion of the STS gene and flanking sequences. The presence of low copy number repeats on either side of the STS gene seems to have a major role in the high frequency of these deletions. Some patients with XLI with terminal deletions of Xp22.3 involving marker DXS1139 and the STS gene show mental retardation (MR); VCX3A is the only gene located on this critical region. OBJECTIVES: To analyse the VCX3A, VCX, VCX2 and VCX3B genes in 80 unrelated Mexican patients with XLI with normal intelligence. METHODS: STS activity was measured in the leucocytes using 7-[3H]-dehydroepiandrosterone sulphate as a substrate. Amplification of the regions from telomeric DXS89 to centromeric DXS1134 including both extremes of the STS and the VCX3A, VCX, VCX2 and VCX3B genes was performed using polymerase chain reaction. RESULTS: No STS activity was detected in the patients with XLI (0.00 pmol mg(-1) protein h(-1)). We observed two different deletion patterns: the first group included 62 patients with deletion of VCX3A and VCX genes. The second group included 18 patients with breakpoints at several regions on either side of the STS gene not including the VCX3A gene. CONCLUSIONS: These data indicate that more complex mechanisms, apart from possible VCX3A gene participation, are occurring in the genesis of MR in XLI, at least in the sample of Mexican patients analysed.
Assuntos
Ictiose Ligada ao Cromossomo X , Ictiose Ligada ao Cromossomo X/genética , Deficiência Intelectual/genética , Proteínas Nucleares/genética , Deleção de Genes , Humanos , Ictiose Ligada ao Cromossomo X/enzimologia , Masculino , México/etnologia , Reação em Cadeia da Polimerase/métodos , Resultado do TratamentoAssuntos
Mutação da Fase de Leitura/genética , Gota/genética , Hiperuricemia/genética , Transportadores de Ânions Orgânicos/genética , Proteínas de Transporte de Cátions Orgânicos/genética , Ácido Úrico/sangue , Adulto , Artrite Gotosa/sangue , Artrite Gotosa/genética , Gota/sangue , Homozigoto , Humanos , Hiperuricemia/sangue , Masculino , Mutagênese Insercional/genéticaAssuntos
Síndrome de Goldenhar/diagnóstico , Ictiose Ligada ao Cromossomo X/diagnóstico , Anormalidades Múltiplas/diagnóstico , Adulto , Criança , Feminino , Seguimentos , Síndrome de Goldenhar/complicações , Humanos , Ictiose Ligada ao Cromossomo X/complicações , Masculino , México , Linhagem , Medição de RiscoRESUMO
X-linked ichthyosis is an inherited disorder due to steroid sulfatase deficiency. It is clinically characterized by dark, adhesive, and regular scales of the skin. Most X-linked ichthyosis patients present large deletions of the STS gene and flanking markers; a minority show a point mutation or partial deletion of the STS gene. In this study we analyzed the STS gene in a family with simultaneous occurrence of X-linked ichthyosis and ichthyosis vulgaris. X-linked ichthyosis diagnosis was confirmed through steroid sulfatase assay in leukocytes using 7-[3H]-dehydroepiandrosterone sulfate as a substrate. Exons 1, 2, 5, and 6-10, and the 5' flanking markers DXS1130, DXS1139, and DXS996 of the STS gene were analyzed by polymerase chain reaction. X-linked ichthyosis patients of the family (n = 4 males) had undetectable levels of STS activity (0.00 pmol per mg protein per h). The DNA analysis showed that only exons 6-10 and the 5' flanking markers of the STS gene were present. We report the first partial deletion of the STS gene spanning exons 1-5 in X-linked ichthyosis patients.
Assuntos
Arilsulfatases/genética , Éxons/genética , Deleção de Genes , Ictiose Ligada ao Cromossomo X/genética , Humanos , Ictiose Vulgar/complicações , Ictiose Ligada ao Cromossomo X/complicações , Masculino , Esteril-SulfataseRESUMO
BACKGROUND: X-linked ichthyosis (XLI) is an inherited disorder due to steroid sulfatase deficiency (STS). Most XLI patients (>90%) have complete deletion of the STS gene and flanking sequences. The presence of low copy number repeats (G1.3 and CRI-S232) on either side of the STS gene seems to play a role in the high frequency of these interstitial deletions. In the present study, we analyzed 80 Mexican patients with XLI and complete deletion of the STS gene. MATERIALS AND METHODS: STS activity was measured in the leukocytes using 7-[(3)H]-dehydroepiandrosterone sulfate as a substrate. Amplification of the regions telomeric-DXS89, DXS996, DXS1139, DXS1130, 5' STS, 3' STS, DXS1131, DXS1133, DXS237, DXS1132, DXF22S1, DXS278, DXS1134-centromeric was performed through PCR. RESULTS: No STS activity was detected in the XLI patients (0.00 pmoles/mg protein/h). We observed 3 different patterns of deletion. The first two groups included 25 and 32 patients, respectively, in which homologous sequences were involved. These subjects showed the 5' STS deletion at the sequence DXS1139, corresponding to the probe CRI-S232A2. The group of 32 patients presented the 3' STS rupture site at the sequence DXF22S1 (probe G1.3) and the remaining 25 patients had the 3' STS breakpoint at the sequence DXS278 (probe CRI-S232B2). The third group included 23 patients with the breakpoints at several regions on either side of the STS gene. No implication of the homologous sequences were observed in this group. CONCLUSION: These data indicate that more complex mechanisms, apart from homologous recombination, are occurring in the genesis of the breakpoints of the STS gene of XLI Mexican patients.
Assuntos
Arilsulfatases/genética , Deleção de Genes , Ictiose Ligada ao Cromossomo X/genética , Arilsulfatases/deficiência , Humanos , Ictiose Ligada ao Cromossomo X/enzimologia , México , Esteril-SulfataseRESUMO
X-linked ichthyosis is an inherited disease due to steroid sulfatase deficiency. Onset is at birth or early after birth with dark, regular, and adherent scales of skin. Approximately 85%-90% of X-linked ichthyosis patients have large deletions of the STS gene and flanking sequences. Three patients have been identified with partial deletions of the gene. Two deletions have been found at the 3' extreme and the other one implicating exons 2-5. This study describes a novel partial deletion of the STS gene in an X-linked ichthyosis patient. The subject was classified through steroid sulfatase assay in leukocytes using 7-[3H]-dehydroepiandrosterone sulfate as a substrate. Exons 1, 2, 5, and 7-10, and 3' flanking sequences DXS1131, DXS1133, DXS237, DXS1132, DXF22S1, and DXS278 of the STS gene were analyzed through polymerase chain reaction. The DNA analysis showed that exon 1 and 3' flanking sequences from DXS237 to DXS278 were present. In this study we report the fourth partial deletion of the STS gene and the first spanning exons 2-10 in X-linked ichthyosis patients.
Assuntos
Arilsulfatases/genética , Ictiose Ligada ao Cromossomo X/genética , Adolescente , Sequência de Bases , Primers do DNA , Éxons , Deleção de Genes , Humanos , Masculino , Mutação Puntual , Reação em Cadeia da Polimerase , Esteril-SulfataseAssuntos
Ictiose Vulgar/genética , Ictiose Ligada ao Cromossomo X/genética , Arilsulfatases/genética , Arilsulfatases/metabolismo , Diagnóstico Diferencial , Feminino , Humanos , Ictiose Vulgar/diagnóstico , Ictiose Vulgar/epidemiologia , Ictiose Ligada ao Cromossomo X/diagnóstico , Ictiose Ligada ao Cromossomo X/epidemiologia , Masculino , México/epidemiologia , Reação em Cadeia da Polimerase , Prevalência , Esteril-SulfataseRESUMO
X-linked ichthyosis is an inherited disease with dark, regular and adherent scales as clinical characteristics. It is caused by a deficiency of the steroid sulphatase enzyme. Steroid sulphatase assay is a relative easy tool that enables correct diagnosis of X-linked ichthyosis patients and carriers. A large number of X-linked ichthyosis patients correspond to non-familial cases that seem to represent de novo mutations. In this study, we examined the X-linked ichthyosis carrier state of the mothers of 42 non-familial cases to determine whether their children corresponded to de novo mutations. To classify patients and carriers, a steroid sulphatase assay was performed in leukocytes using 7-[3H]-dehydroepiandrosterone sulphate as substrate. In 36 mothers (85%) we found steroid sulphatase activity compatible with the carrier state of X-linked ichthyosis. This data suggest that most of the mothers of these patients present the primary gene defect, excluding de novo mutations in the patients.