Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:Q00604 (X-linked)
 16,883 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Menkes' kinky-hair syndrome is an X-linked recessive neurodegenerative and connective-tissue disorder, with decreased serum copper and ceruloplasmin-copper oxidase concentrations and tissue-specific increases in copper content. Clinical manifestations can be related to relative copper deficiency and reduced activity of cuproenzymes in multiple organs. An animal model is provided by mice hemizygous for mutant alleles, such as the blotchy allele, at the X-linked mottled locus. This locus may be homologous in mouse and man. The basic defect is unknown but has been thought to reside in the regulation of the function or synthesis of metallothioneins. In the blotchy mouse and in cultured skin fibroblasts derived therefrom, we showed that the mutation specifically affects the metabolism of copper and not other trace metals. Excessive accumulation and abnormal (reduced) exit kinetics were demonstrated for copper but not for the related trace metals cadmium and zinc. While metallothionein-I messenger RNA (mRNA) concentrations were elevated in blotchy fibroblasts, the elevations in metallothionein-I mRNA in response to metallothionein inducers (cadmium, copper) were similar in blotchy and control cells. Further, metallothionein-I mRNA levels were indistinguishable in mutant and control fibroblasts containing equivalent intracellular copper concentrations. Finally, metallothionein-I mRNA content was not elevated in blotchy kidneys at early developmental stages, before storage of excessive copper. The aggregate data suggest that the basic defect in the blotchy mouse--and, by analogy, in Menkes' syndrome--does not reside in defective modulation of metallothionein function and does not cause abnormal regulation of metallothionein synthesis.
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PMID:Regulation of copper metabolism in the mottled mouse. 367 14

A young adult male is described with muscular dystrophy of probable X-linked recessive inheritance. An onset of muscle weakness in late adolescence was preceded by contractures of the neck and elbows dating back to childhood. The distribution of muscle weakness was proximal in the upper limbs and both proximal and distal in the lower. The mixed pattern of muscle involvement in the legs favours the view that cases of Emery-Dreifuss muscular dystrophy with proximal weakness in both the upper and lower limbs and X-linked scapuloperoneal muscular dystrophy represent the same disorder. A muscle biopsy in the present case showed unique appearances.
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PMID:Emery-Dreifuss syndrome. 370 78

We evaluated 46 carriers of X-linked recessive retinitis pigmentosa for the prevalence of fundus changes, refractive errors, central visual impairment, and electroretinographic abnormalities. Of the 46 carriers, 40 (87%) could be identified by characteristic fundus changes and 37 (86%) of 43 by reductions in electroretinographic amplitude. Interestingly, 36 carriers (78%) had a refractive cylindrical correction of +1.50 diopters (D) or greater in at least one eye, while 25 (54%) had a best corrected visual acuity of 20/30 or less in at least one eye. Fundus examination coupled with an electroretinographic recording was diagnostic of the carrier state in virtually all 46 patients. The presence of a refractive cylinder of +1.50 D or greater should appreciably increase the index of suspicion when assessing the possibility of the carrier state in X-linked retinitis pigmentosa.
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PMID:X-linked recessive retinitis pigmentosa. Clinical characteristics of carriers. 375 83

The plasmalogen ratio (defined as area ratio of lysophosphatidylethanolamine to the diacyl form of phosphatidylethanolamine) was investigated in cultured skin fibroblasts from neonatal adrenoleukodystrophy (N = 4) and X-linked recessive (N = 3) in addition to Zellweger syndrome (N = 3) because plasmalogen was reported to be reduced in Zellweger syndrome. The ratio was markedly decreased in all cases of Zellweger syndrome studied and in three of the four cases of neonatal adrenoleukodystrophy, whereas it was normal in the X-linked cases. This is the first documentation of a plasmalogen deficiency in neonatal adrenoleukodystrophy.
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PMID:Plasmalogen deficiency in cultured skin fibroblasts from neonatal adrenoleukodystrophy. 375 77

Much attention has recently been focused upon the role of linkage analysis in genetic counselling, and enthusiasm has led to some misleading claims. While linkage analysis will undoubtedly play an important role for traits where there are extensive pedigrees of cases, it can achieve nothing where each case is the sole appearance of a mutation. The situation for a lethal recessive X-linked trait lies, in probabilistic terms, close to this latter extreme, particularly in the current world of small families. In view of current practice and research, it seems important to have a precise quantitative assessment of the patterns of carriers and cases generated by such an X-linked lethal mutation, with particular reference to the problem of Duchenne muscular dystrophy. In this paper a branching-process analysis is used to provide such an assessment. This approach has the advantage of requiring neither possibly unrealistic equilibrium assumptions nor assumptions about mutation rates. It also allows the effects of a variety of family size distributions to be analysed. It is found that an X-linked recessive lethal mutation produces few cases (if any), and will do so within a very few generations of its occurrence. Within the usual range of modern family size distributions the mean time to appearance is remarkably constant. The mean number of carriers at the time of the first case is small, as is the expected number of future cases. Except where the family size distribution has large variance, a high proportion of cases are the first in their family.
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PMID:The history of a lethal X-linked mutant. 387 Sep 81

Retinitis pigmentosa (RP), the commonest inherited form of blindness, is a heterogeneous condition which usually manifests as an isolated abnormality, but is occasionally a component of various rare syndromes. The basic defect in RP is unknown, but the recent molecular genetic discovery of linkage with a restriction fragment length polymorphism in X-linked RP offers the potential for carrier screening and antenatal diagnosis of this form of the disorder. In this article we present an overview of RP and an analysis of our findings from a questionnaire survey of 130 affected individuals in 63 families in the Cape Province and Natal. The proportions of the different genetic types of RP were generally in accordance with those found in overseas studies, being 14% autosomal dominant, 9,5% autosomal recessive and 6% X-linked recessive. A further 35% of the affected persons had RP together with other syndromic stigmata, while the remaining 35% could not be classified into any specific genetic category.
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PMID:Retinitis pigmentosa in South Africa. 407 41

Eight unrelated children with centronuclear (myotubular) myopathy are described, ranging in age at the time of diagnosis from 5 days to 12 years. Six had an intrauterine onset and 5 were severely asphyxiated at birth. All had facial involvement and 6 had ophthalmoplegia. Detailed study of the parents in 7 of the families suggested an autosomal recessive inheritance or sporadic occurrence in 2 and X-linked inheritance in 5. Classification in this very variable disorder should be based on severity and mode of presentation together with the genetic pattern, allowing three subgroups to be defined: a severe neonatal X-linked recessive type, a less severe infantile or juvenile autosomal recessive type and a milder autosomal dominant type. For genetic counselling, available relatives should be examined for mild degrees of clinical involvement and morphological abnormalities on needle muscle biopsy.
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PMID:Congenital centronuclear (myotubular) myopathy. A clinical, pathological and genetic study in eight children. 407 80

Practical and scientific aspects of prenatal detection of genetic disorders is discussed. The indications for intrauterine detection of familial biochemical and particular chromosomal disorders require assessment of the risks of transabdominal amniocentesis and of the reliability of diagnosis. A high degree of experience in cultivating amniotic fluid cells and in performing diagnostic tests is required. The obstetrician performing the amniocentesis should be responsible for referring the family to a physician who will perform the abortion. A high-risk group for which amniocentesis may be especially important includes families in which 1 parent is a carrier of a chromosomal rearrangement and in which the woman is a known carrier of an X-linked recessive disorder so that sex determination is important. A moderate-risk group includes women who become pregnant after age 40 in which the risk of having a child with a chromosomal aberration is greater than 1%. A low-risk group includes women over 35 and women who have previously borne a child with trisomic Down's syndrome. The experience gained in over 300 patients suggests that transabdominal aminocentesis carries minimal risks to mother and fetus. Analyses of amniotic fluid obtained by amniocentesis have resulted in antenatal diagnoses of Pompe's disease (deficient alpha-1, 4-glucosidase), Tay-Sachs disease (deficient hexosaminidase A), mucopolysaccharidosis (quantitative and qualitative changes in mucopolysaccharides), methylmalonic aciduria (increased methylamlonate), and adrenogenital syndrome (increase 17-ketosteroids and pregnanetriol). There is a lack of consensus on the reliability of several of these diagnoses resulting from the direct analysis of amniotic fluid. Analyses of uncultured amniotic fluid cells have resulted in diagnoses of Pompe's disease (ultrastructural changes) and Tay-Sachs disease. Analyses of cultivated amniotic fluid cells have enabled diagnoses of galactosemia (deficient galactose-1-phosphate uridyl transferase), X-linked uric aciduria (by autoradiography), lysosomal acid phosphatase deficiency, metachromatic leukodystrophy (deficientaryl sulfatase A), mucopolysaccharidosis, cystic fibrosis (metachromatic granules), and Marfan's syndrome (metachromatic granules). Methylmalonic aciduria has been detected in utero by marternal methymalonate excretion. Adrenogenital syndrome has been detected by urinary estriol.
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PMID:Present status of amniocentesis in intrauterine diagnosis of genetic defects. 511 31

An X-linked recessive disease is reported in a large pedigree. The disease is characterised by a triad of dilated cardiomyopathy, neutropenia and skeletal myopathy. The untreated patients, all boys, died in infancy or early childhood from septicemia or cardiac decompensation. Ultrastructural abnormalities were observed in mitochondria in cardiac muscle cells, neutrophil bone marrow cells and to a lesser extent (0-9%) in skeletal muscle cells. Membrane-bound vacuoles were seen in neutrophil bone marrow cells. Intramuscular fat droplets were increased in type I skeletal muscle fibres. An affected patient had intermittent lactic acidemia, borderline low plasma carnitine, the latter decreasing during periods of illness, and low muscle carnitine (27% pretreatment; 35-40% posttreatment). While on treatment with oral carnitine he had less weakness and no cardiac complaints, but his neutropenia was not affected. Respiratory chain abnormalities were observed in this patient's isolated skeletal muscle mitochondria. These were: (1) diminished concentrations of cytochromes c1 + c, b and aa3 to 29, 47 and 64% of the averaged controls, and (2) a lowered P:0 ratio for oxidation of ascorbate + TMPD, with diminished uncoupler stimulated Mg2+-ATPase activity. Muscle AMP deaminase was deficient (5 resp. 17%). Only one previous report (Neustein et al. 1979) on X-linked mitochondrial cardiomyopathy exists, which probably refers to the same entity. Biochemical studies and haematological abnormalities (neutropenia) are reported for the first time.
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PMID:An X-linked mitochondrial disease affecting cardiac muscle, skeletal muscle and neutrophil leucocytes. 614 97

In this report we describe a Dutch family with ten cases of X-linked recessive congenital hydrocephalus with a high perinatal mortality. In three cases necropsy has confirmed the diagnosis. In the best documented case the most striking features are absence of obstruction or stenosis of the aqueduct and congenital malformation of the cerebral cortex. On the basis of our findings and on reviewing the literature, the hypothesis is put forward that the defective gene on the X-chromosome is responsible for a pathological influence on cerebral cortex development and extraventricular CSF pathways. The expressivity of the genetic defect may be variable, causing extreme phenotypic variants (CHC and/or MR) under the influence of the different modifying genetic or environmental factors. Genetic counselling is difficult in families with no X-linked CHC precedent, since the mutant gene rather produces a communicating HC, secondarily complicated by narrowing of the aqueduct, and as at present there is no way of detecting beforehand heterozygote carriers.
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PMID:X-linked congenital hydrocephalus. 628 5


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