RESUMO
In this study, 103 unrelated South-American patients with mucopolysaccharidosis type II (MPS II) were investigated aiming at the identification of iduronate-2-sulfatase (IDS) disease causing mutations and the possibility of some insights on the genotype-phenotype correlation The strategy used for genotyping involved the identification of the previously reported inversion/disruption of the IDS gene by PCR and screening for other mutations by PCR/SSCP. The exons with altered mobility on SSCP were sequenced, as well as all the exons of patients with no SSCP alteration. By using this strategy, we were able to find the pathogenic mutation in all patients. Alterations such as inversion/disruption and partial/total deletions of the IDS gene were found in 20/103 (19%) patients. Small insertions/deletions/indels (<22 bp) and point mutations were identified in 83/103 (88%) patients, including 30 novel mutations; except for a higher frequency of small duplications in relation to small deletions, the frequencies of major and minor alterations found in our sample are in accordance with those described in the literature.
Assuntos
Éxons , Iduronato Sulfatase/genética , Mucopolissacaridose II/genética , Mutação , Adulto , Feminino , Estudos de Associação Genética , Técnicas de Genotipagem , Humanos , Mucopolissacaridose II/diagnóstico , Mucopolissacaridose II/patologia , Análise de Sequência de DNA , Índice de Gravidade de Doença , América do SulRESUMO
Although the effect of maternal age as a risk factor for Down syndrome (DS) is well known, the role of paternal age in the cause of DS has not been clearly established. To investigate this phenomenon we conducted a case-control study between July 1989 and February 1990. The cases were 318 children and teenagers with DS studied at the Specialized Educational Institutions of Lima City, Perú. They were paired with 1,196 control individuals that were selected from the birth records of 2 general hospitals of the city. For each case we tried to obtain 4 controls, paired by their date of birth, sex, and maternal age. The means of paternal age in the 2 groups were compared, first globally and then by groups of maternal age (< 21 years, 21-29 years, 30-34 years, 35-39 years and > 39 years). None of the comparisons gave a statistically significant difference between the 2 groups, using either the Student t-test or the Mann-Whitney U-test. The results obtained in this study give no evidence that paternal age can be considered a risk factor for the conception of a child with DS.
Assuntos
Síndrome de Down/epidemiologia , Idade Paterna , Adulto , Estudos de Casos e Controles , Feminino , Humanos , Recém-Nascido , Masculino , Idade Materna , Pessoa de Meia-Idade , Peru/epidemiologia , Gravidez , Fatores de RiscoRESUMO
The aim of this work is to reevaluate the hypothesis of the existence of a possible genetic control of nondisjunction of chromosome 21. The population under study was the families trisomy (TLI) as diagnosed in the Medical Genetic Unit of LUZ from 1971 to 1988. The control population was the families of 418 individuals with no apparent genetic pathology (CON), approximately matched in age with the patients. The frequency of consanguineous unions in parents (UCPM), maternal grandparents (UCAM) and paternal grandparents (UCAP) of both patients and controls was determined. The results indicated that UCPM was significantly greater in TLI than CON while the UCAM and UCAP were more frequent in CON. The coefficient of consanguinity in parents of TLI was three times greater than in parents of CON. The results of this investigation suggest that the consanguinity should be considered another risk factor for the nondisjunction of chromosome 21 and it is independent of maternal age and support the hypothesis that there exists an autosomal recessive gene that, in the homologous state, results in a predisposition toward nondisjunction of chromosome 21 in the first mitotic division.
Assuntos
Consanguinidade , Síndrome de Down/genética , Genealogia e Heráldica , Humanos , Idade Materna , Fatores de RiscoRESUMO
We report a boy with a de novo terminal deletion of chromosome 4q, (q31----qter) and compare him to 17 previously reported cases with the same anomaly. This case contributes further to the delineation of the del(4)(q31) phenotype, which seems to be clinically recognizable.