Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

X-linked hypophosphatemia is a genetic bone disease in humans and mice. Two closely linked mutations in mice, Hyp and Gy, cause low plasma phosphate and a rachitic and osteomalacic bone disease. Because of the controversy as to whether Gy is a good model for X-linked hypophosphatemia, the phenotypic severity of these two mutations was compared in both sexes and on two genetic backgrounds. The depression in plasma levels of phosphate was similar in all 10-week-old mutant mice. Male Hyp mice and heterozygous female Hyp mice were affected with similar severity in terms of reduced tail growth, shortened femora, reduced femoral mineral content, and abnormal mineral composition of the femoral matrix. In contrast, male Gy mice did not survive on the C57BL/6J background and were more severely affected than female Gy mice on the B6C3H background. The hybrid B6C3H background ameliorated the bone disease compared with the inbred C57BL/6J background for both mutant strains. There was no evidence of change in the plasma levels of 1,25-dihydroxyvitamin D, duodenal level of vitamin D-dependent calcium-binding protein, or urinary level of calcium in these adult mutant mice. In summary, Gy mice have a sexual dimorphism not present in Hyp mice. These two genes may indicate the presence of multiple gene loci in the human disease, with multiple proteins involved in the pathophysiology of the bone disease.
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PMID:Femoral abnormalities and vitamin D metabolism in X-linked hypophosphatemic (Hyp and Gy) mice. 785 1

The hypothesis that chromosomal region Xq27-28 harbours a gene for manic-depression has been a focus of interest in human genetics. X-linked inheritance of manic depressive illness has been re-examined in 3 multigeneration Israeli kindreds. Extension and re-evaluation of pedigree data, including new individuals, diagnostic follow-up, and analysis with DNA markers, shows greatly diminished support for linkage to Xq28. The peak lod scores in two of the pedigrees have dropped several lod units to clearly negative values at the RCP-F8-G6PD gene cluster. On the other hand, positive lod scores (Zmax = 2.09) are sustained in another pedigree at the same map location. None of the pedigrees show linkage to more proximal markers, including the Xq27 locus DXS98. Our analysis underscores the uncertainties in studying complex disorders.
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PMID:Diminished support for linkage between manic depressive illness and X-chromosome markers in three Israeli pedigrees. 849 Jun 52

A captive colony of collared lemmings (Dicrostonyx groenlandicus) from northern Alaska produced a male-biased sex ratio of 67% males for about three generations. These lemmings have a pair of autosomes fused to the sex chromosomes. Thus, males have two copies of some (formerly autosomal) sex-linked genes: One set is X-linked; the other can be described as Y-linked. Given such a karyotype, deleterious recessive alleles on the autosomal portion of the X chromosome are more resistant to selection than truly autosomal loci because they can be eliminated by homozygosity only in females. The male-bias could have resulted from one or more lethals carried on the formerly autosomal arm of the X chromosome. As inbreeding coefficients approached 0.3, the lethal was apparently homozygous in half of the homogametic (female) zygotes. This phenomenon may explain the excess of males and XY females attributed to meiotic drive in Dicrostonyx torquatus from Siberia. If under the natural mating system, inbreeding depression limits fitness, then fusion of autosomal chromatin to the sex chromosomes could be an adaptation to reduce inbreeding depression in heterogametic individuals.
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PMID:A male-biased natal sex-ratio in inbred collared lemmings, Dicrostonyx groenlandicus. 968 38

The 22 antigens of the Kell blood group system are located on a red blood cell (RBC) membrane glycoprotein that shows sequence homology with a family of metalloendopeptidases. Expression of the Kell system antigens is partially governed by XK, an X-linked gene that encodes the Kx protein; absence of Kx results in reduced Kell antigen expression. Almost total absence of Kell antigens from the RBCs of a German man with no symptoms of neuroacanthocytosis could not be due to the Kell-null phenotype, Ko, because his RBCs had very weak expression of Kx antigen and his three children were Kp(a + b+). Kell antigens were normal on the RBCs of his son but weak on those of his two daughters. An Nla III restriction fragment-length polymorphism within the KEL gene showed the Kpa/Kpa genotype in the propositus. Sequencing of his XK gene showed a single base change within the donor splice consensus sequence of intron 2. A BsaAl restriction fragment-length polymorphism showed the mutation in both of his daughters but not in his son. The extreme depression of the Kell antigens of the propositus must be due to a combination of effects, ie, homozygosity for Kpa and deficiency of Kx protein, each of which is capable of causing some degree of weakening of Kell antigens.
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PMID:A combination of the effects of rare genotypes at the XK and KEL blood group loci results in absence of Kell system antigens from the red blood cells. 891 72

We present the case of a 51-year-old patient with a 31-year history of psychiatric symptoms, craniocervical dystonia, bulbar dysfunction, and parkinsonism. His dystonic movements included blepharospasm, jaw opening and lingual dystonia, and spasmodic retrocollis. Psychiatric symptoms included psychosis and depression, with onset years before the movement disorder. After his death by aspiration, examination of his brain revealed abnormalities limited to the neostriatum. Staining of brain sections, including Holzer, glial fibrillary acidic protein, and immunohistochemical stain for calbindin D28k, revealed the presence of a mosaic pattern of gliosis with neuronal loss (sparing large neurons) within this region. The islands of tissue between stands of gliosis had a normal appearance. This patient represents only the fourth case (and first North American born) with a mosaic pattern of gliosis in the neostriatum. The clinical and pathologic features were similar in all four cases except that our patient was the first with prominent psychiatric symptoms and a more stable, less progressive course. Mosaicism has been described in the X-linked Filipino disorder Lubag. Occurrence in non-Filipino patients, such as ours, suggest that either Lubag can develop in non-Filipino families or that mosaicism is a nonspecific pathologic finding in some patients with idiopathic dystonia. Finally, our case reports the notion that craniocervical dystonia may result from neostriatal dysfunction.
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PMID:Mosaic pattern of gliosis in the neostriatum of a North American man with craniocervical dystonia and parkinsonism. 938 67

A nationwide search for patients with Alport syndrome (AS), a hereditary nephritis with sensorineural hearing loss and occasional ocular anomalies, was performed. As AS is usually transmitted in an X-linked fashion, its form is usually severe in male and mild in female patients. Semi-structured interviews were conducted with 24 patients with AS and their family members from 17 families and 11 pedigrees. The emphasis was on psychosocial stress experienced in everyday life, as well as the influence of AS on family relationships, especially mother-son relationships. Special attention was paid to children's reactions and feelings as well as the coping strategies of the family. Denial was the most common psychological defence found in our study. We found several cases where AS had led to chronic mental suffering. One of the patterns was a combination of maternal depression and an overprotective attitude toward an AS-affected son. In other instances, depressive symptomatology and anxiety were seen in connection with complications and an adverse outcome of the disease. Families with any AS manifestations should be encouraged to discuss openly the past histories of family members, their fears, feelings of guilt, hopes and expectations. The role and empathic attitude of the clinician is crucial in this process. Mildly affected mothers who have sons with AS are especially in need of psychological support. Professional psychological help should be made available but not given routinely.
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PMID:Psychosocial impact of an X-linked hereditary disease: a study of Alport syndrome patients and family members. 1092 41

Hyperimmunoglobulin M (IgM) syndrome is a rare primary immunodeficiency disorder, and the non-X-linked form of this syndrome is even more infrequent. We report the clinical case of a 6-year-old girl. Her disease began at the age of 1 year when she experienced bronchial obstruction. When she was 3 years old she developed severe recurrent respiratory infections of unusual clinical course. Serum IgM was elevated and the other serum immunoglobulins were absent. Cellular immune response was impaired, with severe depression of delayed hypersensitive cutaneous response and of proliferative response to mitogens. The CD40 ligand expression decreased. Chest CT scan showed areas of lung condensation, bronchial dilatation and signs suggesting interstitial pneumonitis. The latter was confirmed by a biopsy showing a high number of Langerhans' cells and an early-stage fibrosis. She was treated with antibiotics, inhaled bronchodilators and corticosteroids, intravenous immunoglobulin, chloroquine and prednisone. Despite the substitution therapy, her clinical course was slow, with respiratory infections and oxygen dependance. The follow-up thoracoscopic biopsy performed after 18 months of immunosuppressant therapy showed a progression of fibrosis and a decrease in the inflammatory infiltrate.
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PMID:Non-X-linked hyperimmunoglobulin M syndrome with chronic interstitial pneumonitis. 1120 40

The McLeod syndrome is an X-linked disorder caused by mutations of the XK gene encoding the XK protein. The syndrome is characterized by absent Kx erythrocyte antigen, weak expression of Kell blood group system antigens, and acanthocytosis. In some allelic variants, elevated creatine kinase, myopathy, neurogenic muscle atrophy, and progressive chorea are found. We describe a family with a novel point mutation in the XK gene consisting of a C to T base transition at nucleotide position 977, introducing a stop codon. Among seven affected males, five manifested with psychiatric disorders such as depression, bipolar disorder, or personality disorder, but only two presented with chorea Positron emission tomography and magnetic resonance volumetry revealed reduced striatal 2-fluoro-2-deoxy-glucose (FDG) uptake and diminished volumes of the caudate nucleus and putamen that correlated with disease duration. In contrast, none of 12 female mutation carriers showed psychiatric or movement disorders. However, a semidominant effect of the mutation was suggested by erythrocyte and blood group mosaicism and reduced striatal FDG uptake without structural abnormalities. Therefore, patients with psychiatric signs or symptoms segregating in an X-linked trait should be examined for acanthocytosis and Kell/Kx blood group serology.
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PMID:McLeod syndrome: a novel mutation, predominant psychiatric manifestations, and distinct striatal imaging findings. 1126 14

Pelizaeus Merzbacher disease is an X-linked dysmyelinating disorder of the CNS, resulting from mutations in the proteolipid protein (PLP) gene. An animal model for this disorder, the myelin-deficient (MD) rat, carries a point mutation in the PLP gene and exhibits a phenotype similar to the fatal, connatal disease, including extensive dysmyelination, tremors, ataxia, and death at approximately postnatal day 21 (P21). We postulated that early death might result from disruption of myelinated neural pathways in the caudal brainstem and altered ventilatory response to oxygen deprivation or hypercapnic stimulus. Using barometric plethysmography to measure respiratory function, we found that the MD rat develops lethal hypoxic depression of breathing at P21, but hypercapnic ventilatory response is normal. Histologic examination of the caudal brainstem in the MD rat at this age showed extensive dysmyelination and downregulation of NMDA and to a lesser extent GABA(A) receptors on neurons in the nucleus tractus solitarius, hypoglossal nucleus, and dorsal motor nucleus of the vagus. Unexpectedly, immunoreactive PLP/DM20 was detected in neurons in the caudal brainstem. Not all biosynthetic functions and structural elements were altered in these neurons, because phosphorylated and nonphosphorylated neurofilament and choline acetyltransferase expression were comparable between MD and wild-type rats. These findings suggest that PLP is expressed in neurons in the developing brainstem and that PLP gene mutation can selectively disrupt central processing of afferent neural input from peripheral chemoreceptors, leaving the central chemosensory system for hypercapnia intact.
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PMID:Proteolipid protein gene mutation induces altered ventilatory response to hypoxia in the myelin-deficient rat. 1265 85

We have identified truncating mutations in the human DLG3 (neuroendocrine dlg) gene in 4 of 329 families with moderate to severe X-linked mental retardation. DLG3 encodes synapse-associated protein 102 (SAP102), a member of the membrane-associated guanylate kinase protein family. Neuronal SAP102 is expressed during early brain development and is localized to the postsynaptic density of excitatory synapses. It is composed of three amino-terminal PDZ domains, an src homology domain, and a carboxyl-terminal guanylate kinase domain. The PDZ domains interact directly with the NR2 subunits of the NMDA glutamate receptor and with other proteins responsible for NMDA receptor localization, immobilization, and signaling. The mutations identified in this study all introduce premature stop codons within or before the third PDZ domain, and it is likely that this impairs the ability of SAP102 to interact with the NMDA receptor and/or other proteins involved in downstream NMDA receptor signaling pathways. NMDA receptors have been implicated in the induction of certain forms of synaptic plasticity, such as long-term potentiation and long-term depression, and these changes in synaptic efficacy have been proposed as neural mechanisms underlying memory and learning. The disruption of NMDA receptor targeting or signaling, as a result of the loss of SAP102, may lead to altered synaptic plasticity and may explain the intellectual impairment observed in individuals with DLG3 mutations.
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PMID:Mutations in the DLG3 gene cause nonsyndromic X-linked mental retardation. 1518 69


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