Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Alleles for the single human nerve growth factor receptor gene (NGFR) on chromosome 17q can be distinguished by two polymorphic restriction sites for XmnI and one for HincII. The combined information content for haplotypes is quite high, making the NGFR locus an excellent genetic marker. Two of these polymorphisms were used to follow the inheritance of NGFR alleles in families with two or more members affected with familial dysautonomia. This rare disease is inherited in an autosomal recessive mode in the Ashkenazic Jewish population. Affected individuals show a severe depletion of NGF-dependent nerve populations from birth. Linkage analysis excluded a role for NGFR in this disease with odds of greater than 10(6):1 against the dysautonomia gene being within 1 centiMorgan of the mutation. In a previous study the gene for the beta subunit of NGF (NGFB) was also excluded in this disease. A possible role for other genes involved in NGF action or those coding for other developmentally determining neuronal factors is indicated.
Mol Biol Med 1986 Dec
PMID:DNA polymorphisms for the nerve growth factor receptor gene exclude its role in familial dysautonomia. 288 91

Steroid 17 alpha-hydroxylase (cytochrome P-450(17)alpha) mediates both 17 alpha-hydroxylase and 17,20-lyase activities. A relatively rare disease, 17 alpha-hydroxylase deficiency is characterized by defects in either or both of these activities. The molecular basis for variability of the defect is not well understood. We have determined the exonic sequence of the mutant P-450(17)alpha gene from one Japanese patient with combined 17 alpha-hydroxylase/17,20-lyase deficiencies. A stop codon (TGA) due to a single point mutation was found at the position of amino acid 17 in exon 1 of the P-450(17)alpha gene. The presence of a stop codon in the N-terminal region of this gene leads to the absence of a functional P-450(17)alpha protein in adrenal cortex and ovary, and consequently hypertension, primary amenorrhea and osteoporosis in this patient.
Mol Cell Endocrinol 1988 Oct
PMID:Combined 17 alpha-hydroxylase/17,20-lyase deficiency due to a stop codon in the N-terminal region of 17 alpha-hydroxylase cytochrome P-450. 326 89

Positional cloning of rare disease genes depends on the availability of highly polymorphic markers near the disease loci. The most abundant class of polymorphic markers in the human genome is CA-repeats. We have developed a strategy for the rapid isolation of highly polymorphic CA-repeats from YAC clones. Total DNA of yeast clones containing partly overlapping YACs is digested with frequent cutter restriction enzymes, blotted and hybridized with a poly(CA/GT) probe under high stringency conditions that enable preferential detection of long CA-repeats. The repeats detected in this way are isolated by PCR using vectorette linkers, sequenced, and appropriate flanking markers are constructed for genotyping. All of the CA-repeats identified using this approach were highly polymorphic. This simple and rapid approach should allow the development of highly polymorphic markers at any genomic region cloned in YACs.
Mol Biotechnol 1995 Apr
PMID:Rapid identification of polymorphic CA-repeats in YAC clones. 762 Sep 80

Among glycolytic enzyme defects, hexokinase (ATP: D-hexose 6-phosphotransferase, EC 2.7.1.1; HK) deficiency is a very rare disease where the predominant clinical effect is nonspherocytic hemolytic anemia. Here we report the characterization at molecular level of the HK type I cDNA from a patient with hemolytic anemia due to hexokinase deficiency. PCR amplification and sequence of the cDNA revealed the presence of a deletion and of a single nucleotide substitution, both in heterozygous form. In particular, the deletion, 96 bp long, concerns nucleotides 577 to 672 in the HK cDNA sequence and was never found in the cDNAs of 14 unrelated normal subjects. The sequence of the HK allele without deletion showed a single nucleotide substitution from T to C at position 1667 which causes the amino acid change from Leu529 to Ser. This heterozygous mutation at nt 1667 was confirmed by direct sequencing of the patient genomic DNA, but when DNAs from 10 normal controls were examined by this technique the substitution at nt 1667 was never found. From these results we concluded that the patient is carrying a point mutation at nt 1667 of one HK allele and a 96 nt deletion in the other allele. In normal subjects two differences from the published cDNA sequence were documented.
Blood Cells Mol Dis 1995
PMID:Hexokinase mutations that produce nonspherocytic hemolytic anemia. 765 56

Malignant mesothelioma in humans is a rare disease, but it has recently received much public attention and concern because of its strong relationship to exposure to asbestos. We have found overexpression of the gene for platelet-derived growth factor (PDGF)-beta in several mesothelioma xenografts in nude mice. Because some mesothelioma cell lines such as VAMT-1 overexpress PDGF-beta and PDGF-beta receptors, it was considered that an autocrine loop involving PDGF-beta and its receptor may contribute to the malignant phenotype of these cells. To investigate this possibility we have developed a hammerhead ribozyme against PDGF-beta mRNA. This c-sis ribozyme was able to cleave an artificial PDGF-beta RNA substrate in a cell-free system. Transduction of this ribozyme, with the aid of a constitutive expression vector, in the VAMT-1 cell line led to a decrease in the PDGF-beta mRNA level. The ribozyme expressed in these cells was functional in cleaving the artificial RNA substrate in vitro. Ribonuclease protection assays using the ribozyme and whole PDGF-beta mRNA showed that this ribozyme was capable of cleaving the whole mRNA in vivo. Transfectant clones containing the wild-type ribozyme showed decreased cell growth, in parallel with the decreases in PDGF-beta expression. The disabled ribozyme was inactive in the cleavage reaction in vitro and in decreasing the cell growth rate in vivo. Our data indicate that in some mesothelioma cells the PDGF-beta autocrine loop may be functional and transduction of the PDGF-beta ribozyme leads to a significant reduction of cell growth. The c-sis ribozyme may be applicable in the treatment of patients with malignant mesothelioma.
Mol Pharmacol 1994 Sep
PMID:Modulation of platelet-derived growth factor-beta mRNA expression and cell growth in a human mesothelioma cell line by a hammerhead ribozyme. 793 23

Congenital nephrogenic diabetes insipidus (NDI) is a rare disease caused most often by mutations in the vasopressin V2 receptor (AVPR2). We studied a family which included a female patient with NDI with symptoms dating from infancy. The patient responded to large doses of desmopressin (dDAVP) which decreased urine volume from 10 to 4 I/day. Neither the parents nor the three sisters were polyuric. The patient was found to be a compound heterozygote for two novel recessive point mutations in the aquaporin-2 (AQP2) gene: L22V in exon 1 and C181W in exon 3. Residue Cys181 in AQP2 is the site for inhibition of water permeation by mercurial compounds and is located near to the NPA motif conserved in all aquaporins. Osmotic water permeability (Pf) in Xenopus oocytes injected with cRNA encoding C181W-AQP2 was not increased over water control, while expression of L22V cRNA increased the Pf to approximately 60% of that for wild-type AQP2. Co-injection of the mutant cRNAs with the wild-type cRNA did not affect the function of the wild-type AQP2. Immunolocalization of AQP2-transfected CHO cells showed that the C181W mutant had an endoplasmic reticulum-like intracellular distribution, whereas L22V and wild-type AQP2 showed endosome and plasma membrane staining. Water permeability assays showed a high Pf in cells expressing wild-type and L22V AQP2. This study indicates that AQP2 mutations can confer partially responsive NDI.
Hum Mol Genet 1997 Oct
PMID:Identification and characterization of aquaporin-2 water channel mutations causing nephrogenic diabetes insipidus with partial vasopressin response. 930 64

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is a rare disease in North China. In the present investigation, DNA samples from 17 patients with G6PD deficiency from Tianjin area in North China were studied for the two G6PD common mutations (R459L and R463H) and two single nucleotide polymorphisms (1311C/T and 1365-13T/C) using a dideoxy fingerprinting method. Five patients were positive for mutation R459L, and six patients were positive for mutation R463H. Further haplotype analyses using three flanking dinucleotide repeat polymorphism loci, DXS1123, DXS1113, and F8C(IVS13), were performed on 14 patient families and 16 control Chinese females. The results indicated that the two common mutations were from different haplotypes. Also, the data suggested a possible allelic association between the two G6PD common mutations and the F8C(IVS13) locus and a different allelic distribution for loci DXS1113 and F8C(IVS13) between Chinese and Caucasian populations.
Biochem Mol Biol Int 1998 Dec
PMID:Analysis of common mutations and associated haplotypes in Chinese patients with glucose-6-phosphate dehydrogenase deficiency. 989 46

The reports of congenital estrogen deficiency - notably, estrogen resistance and aromatase deficiency - have completely changed our knowledge on the role of estrogen on bone in males. Particularly, the bone changes at puberty, which were classically considered androgen-dependent, are now considered to be induced at least in part by estrogen action. Clinical cases of congenital estrogen deficiency have clearly demonstrated that the role of estrogens in epiphyseal closure, skeletal proportions and bone mineralization is crucial not only in women but also in men. In addition progress have been made in the treatment of such a rare disease even though further studies are needed to a definitive understanding of this issue.
Mol Cell Endocrinol 2001 Jun 10
PMID:Role of estrogen on bone in the human male: insights from the natural models of congenital estrogen deficiency. 1140 12

Pulmonary alveolar proteinosis (PAP) is a rare disease characterized by the accumulation of phospholipids and surfactant proteins in the lung. The central role for granulocyte-macrophage colony-stimulating factor (GM-CSF) in surfactant homeostasis has been established in mice lacking the GM-CSF gene, which results in murine pulmonary alveolar proteinosis. No GM-CSF gene defect has been defined in adult patients with idiopathic PAP. Previous studies indicated that the human disease differs from the murine model by the presence of circulating, neutralizing autoantibodies against GM-CSF. Therefore, the final common pathway between the GM-CSF knockout and human PAP appears to be the deficiency of functionally active GM-CSF. In the present study, all patients with idiopathic PAP were found to have systemic and localized antibodies against GM-CSF. Anti-GM-CSF titers were a specific and sensitive marker for PAP. In addition, we present data showing that the absence of active GM-CSF is associated with enhanced levels of macrophage colony-stimulating factor, monocyte chemoattractant protein-1, and interleukin-8. These studies confirm and strengthen previous studies and support the concept that adult idiopathic PAP is an autoimmune disease defined by the presence of anti-GM-CSF. Further, using anti-GM-CSF as an indicator of pulmonary alveolar proteinosis may avoid the use of more invasive means of evaluating patients with pulmonary disease characterized by alveolar infiltrates.
Am J Respir Cell Mol Biol 2002 Oct
PMID:Autoantibodies against granulocyte macrophage colony-stimulating factor are diagnostic for pulmonary alveolar proteinosis. 1235 82

Neuroferritinopathy is a recently recognised genetic disease resulting in a dominantly inherited movement disorder. The condition was mapped by linkage analysis to chromosome 19q13.3 and found to be due to a single adenine insertion in the ferritin light chain (FTL) gene at position 460-461 which is predicted to alter the C terminus of the FTL polypeptide. Clinical features of neuroferritinopathy are highly variable, with chorea, dystonia, and Parkinsonian features predominating in different affected individuals. The most consistent feature is a dystonic dysarthria. Symptoms and abnormal physical signs appear to be restricted to the nervous system and onset is typically in the fourth to sixth decades. Low serum ferritin also characterises this condition. Brain MR imaging of affected patients demonstrates iron deposition in the basal ganglia, progressing over years to cystic degeneration, and brain histochemistry shows abnormal aggregates of ferritin and iron. Now that the molecular basis of the condition is known, therapeutic interventions to reduce or reverse brain iron deposition are being evaluated. This rare disease provides evidence of a central role for iron metabolism in neurodegenerative disorders.
Blood Cells Mol Dis
PMID:Neuroferritinopathy: a window on the role of iron in neurodegeneration. 1254 46


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