RESUMO
Fifty-three pedigrees with the fragile X syndrome have been studied for amplification of the CGG repeat sequence adjacent to the CpG island in the FMR1 gene. Probe StB12.3 allowed direct detection of affected males, carrier females, normal transmitting males, as well as prenatal diagnosis. Comparison of our molecular data with our previous linkage data from 38 families indicates the effectiveness of direct DNA analysis. A total of 325 individuals were studied and no new mutation was found. All daughters of males with a premutation had a premutation. When the mother had a full mutation no children had a premutation. In premutated mothers, the size of the premutation seems to be a determining factor for the transition to the full mutation. All affected males had a full mutation or mosaicism and only 42% of the females with a full mutation were mentally impaired. Analysis of large families over 3 generations illustrated clearly the Sherman paradox. Furthermore, the analysis of these families is in reasonable agreement with the multiallelic model of Morton and Macpherson [Proc Natl Acad Sci USA 89:4215-4217, 1992]. Mosaic cases in the offspring of the mothers with a full mutation suggest a maternal germinal mosaicism. Then an abnormal methylation and a somatic heterogeneity established in very early steps of embryogenesis could explain these cases.
Assuntos
Sondas de DNA , Síndrome do Cromossomo X Frágil/genética , Alelos , Saúde da Família , Feminino , Síndrome do Cromossomo X Frágil/diagnóstico , Ligação Genética , Marcadores Genéticos , Heterozigoto , Humanos , Masculino , Mutação , Linhagem , Gravidez , Diagnóstico Pré-NatalRESUMO
A new automatic EMG analysis and on-line assignment of MUAP into 8 dynamic cluster algorithm classes (P1......P8) were applied to female relatives of patients with Duchenne type dystrophy. Promising results are given. MUAP amplitude and duration differed significantly in the female relatives compared to the control subjects. MUAP distribution patterns found in the carrier population were significantly different from those found in controls; the carrier population exhibited higher percentages of MUAP (than healthy subjects) in the classes where were assigned the great majority of the potentials obtained from patients with Duchenne type dystrophy. All the known carriers and 55.5% of the possible carriers were detected using these methods. Nevertheless, the absolute accuracy of the results cannot yet be considered achieved because no recognizable distribution pattern was observed in carrier's daughters. No correlation was found between CK levels and EMG distribution.
Assuntos
Eletromiografia/métodos , Distrofias Musculares/diagnóstico , Adulto , Fatores Etários , Creatina Quinase/sangue , Feminino , Triagem de Portadores Genéticos/métodos , Humanos , Pessoa de Meia-IdadeRESUMO
A new family is reported of a Bickers-Adams-Edwards syndrome. This family has been studied up to three generations. Two female carriers are known. Among the six male children who are affected, four are severely mentally retarded, have spasticity of the legs, and survived with a mild macrocephaly, and two show a more severe and rapid progression of head enlargement. A partial aqueductal stenosis, with remarkable ventricular dilatation, has been demonstrated by pneumoence-phalography in three boys. A deformity of the thumbs links these six children together. One of them has been treated by a ventriculoperitoneal shunt, when 18 months old, without any improvement in the neurological condition. The mental deficiency is much more severe than could be expected from the degree of hydrocephalus, at least as estimated clinically by the macrocephaly. Hydrocephalus is precocious, and the ventricular dilatation very advanced when seen by PEG studies. Recognition of the female carriers is not possible.
Assuntos
Aqueduto do Mesencéfalo/anormalidades , Hidrocefalia/genética , Deficiência Intelectual/genética , Cromossomos Sexuais , Polegar/anormalidades , Adolescente , Adulto , Pré-Escolar , Feminino , Genes Recessivos , Humanos , Masculino , Linhagem , Fatores Sexuais , SíndromeRESUMO
The authors report a clinical and radiographic course of a 16 years old caucasian girl with a progressive deformation of her skeleton. The primary lesions occur in knees and wrists. This disease was at first considered as a rheumatoid arthritis, then as a dysplasia epiphysialis multiplex, and now as essential deformans osteolysis (with carpal lysis, shortening of the forearm bones, dislocation of the elbows, disparition of the humeral and femoral heads, contracture of hips and knees, posterior tarsal lysis, and kypho-scoliosis). The clinical (particularly ophtalmologic), biological (including inflammatory, phospho-calcic and nephrologic evaluation with mucopolysaccharidosis urinary excretion) and histological (skin, muscle and bone) check-up were normal. They review the different classification established on lesion topography, on association or not with a nephropathy, finally on an dominant or recessive autosomal inheritance. Then the authors think that their case is similar to the ones of Winchester and Hollister. They discuss the etiopathogenic factors, and do not consider their case as a new mucopolysaccharidosis, but rather as a generalized disease of the collagen of bones.
Assuntos
Reabsorção Óssea/diagnóstico por imagem , Osteólise Essencial/diagnóstico por imagem , Adolescente , Artrite Reumatoide/diagnóstico por imagem , Condrodisplasia Punctata/diagnóstico por imagem , Diagnóstico Diferencial , Feminino , Humanos , Osteólise Essencial/metabolismo , Radiografia , SíndromeRESUMO
Hydrocephalus is a frequent complication of spina bifida. We wanted to find out if the risk of isolated hydrocephalus was greater in families with NTD (anencephaly and spina bifida) from 424 families studied between 1975 and 1984 in Brittany. The risk of recurrence of NTD is 1.8% in these families, the risk of hydrocephalus 0.3% which represents a risk three times greater than that of the population at large. This risk seems all the higher if the proband is a spina bifida of the male sex. However, no X-linked heredity can be reasonably assumed in these cases. We conclude that these families present a higher multifactorial risk of having another malformed child.
Assuntos
Anencefalia/genética , Hidrocefalia/genética , Espinha Bífida Oculta/genética , Anencefalia/complicações , Causalidade , Feminino , França , Humanos , Hidrocefalia/epidemiologia , Masculino , Risco , Espinha Bífida Oculta/complicaçõesRESUMO
Among the central nervous system (CNS) dysmyelinating disorders, Pelizaeus-Merzbacher disease (PMD) has been individualized by its X-linked mode of inheritance and the existence of corresponding animal models. Mutations in the major myelin proteolipid (PLP) gene coding for PLP and its splicing variant DM20 protein, have been demonstrated in animal mutants and more recently in PMD affected patients. We have identified, in a two-generation PMD affected family, an insertion/deletion event in the exon IV of the PLP gene, leading to the synthesis of predicted truncated PLP and DM20 proteins with altered carboxyl terminal end. This is the first report of a frameshift mutation in the PLP gene in PMD.