Assuntos
Códon sem Sentido , Ictiose Ligada ao Cromossomo X/genética , Esteril-Sulfatase/genética , Criança , Análise Mutacional de DNA , Bases de Dados de Proteínas , Predisposição Genética para Doença , Hereditariedade , Humanos , Ictiose Ligada ao Cromossomo X/diagnóstico , Ictiose Ligada ao Cromossomo X/enzimologia , Masculino , Modelos Moleculares , Linhagem , Fenótipo , Conformação Proteica , Esteril-Sulfatase/química , Esteril-Sulfatase/metabolismo , Relação Estrutura-AtividadeRESUMO
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 TratamentoRESUMO
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 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.
Assuntos
Arilsulfatases/sangue , Ictiose Ligada ao Cromossomo X/diagnóstico , Ictiose Ligada ao Cromossomo X/genética , Mutação , Arilsulfatases/deficiência , Arilsulfatases/genética , Feminino , Humanos , Ictiose Ligada ao Cromossomo X/enzimologia , Masculino , Linhagem , Esteril-SulfataseRESUMO
The present study analyzes the frequency of molecular deletions in the steroid sulfatase (STS) encoding gene in a sample of 50 Mexican subjects with biochemical diagnosis of X-linked ichthyosis (XLI). To establish the correct diagnosis, STS activity was determined in leukocytes using 7-(3)H-dehydroepiandrosterone sulfate as the substrate. No amplification of the 3' and 5' ends of the STS gene by PCR was detected in the DNA of 49 patients, whereas only one sample of 50 presented a normal amplification. This report shows a very high frequency of deletions in the human STS encoding gene in a representative sample of the Mexican population, and it defines the characteristics of XLI in patients whose STS gene has a complete deletion as a major molecular defect.
Assuntos
Arilsulfatases/genética , Deleção de Genes , Ictiose Ligada ao Cromossomo X/genética , Frequência do Gene , Humanos , Ictiose Ligada ao Cromossomo X/enzimologia , México , Reação em Cadeia da Polimerase , Esteril-SulfataseRESUMO
Nas ictioses recessivas ligadas ao x (IRLX) ocorre deficiência ou ausência de atividade da enzima colesterol-sulfatase (arilsulfatase C). A descamaçäo da camada córnea é retardada, determinando quadro clínico característico. Com base em um caso clínico de IRLX, säo discutidos os aspectos clínicos, bioquímicos e genéticos dessa forma de ictiose