Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0022716 (Menkes)
 1,057 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Fibroblast cultures from 12 unrelated patients with classical Menkes disease were analyzed for mutations in the MNK gene, by reverse transcription-PCR (RT-PCR) and chemical cleavage mismatch detection. Mutations were observed in 10 patients, and in each case a different mutation was present. All of the mutations would be predicted to have adverse effects on protein expression. Mutations that resulted in splicing abnormalities, detected by RT-PCR alone, were observed in six patients and included two splice-site changes, a nonsense mutation, a missense mutation, a small duplication, and a small deletion. Chemical cleavage analysis of the remaining six patients revealed the presence of one nonsense mutation, two adjacent 5-bp deletions, and one missense mutation. A valine/leucine polymorphism was also observed. These findings, combined with the prior observation of deletions in 15%-20% of Menkes patients, suggest that Southern blot hybridization and RT-PCR will identify mutations in the majority of patients.
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PMID:Diverse mutations in patients with Menkes disease often lead to exon skipping. 797 50

Maple syrup urine disease (MSUD) was first described in 1954 by Menkes et al. as a progressive neurologic degenerative disorder. In 1960, Dancis et al. established that the metabolic block in MSUD is at the decarboxylation of branched-chain alpha-ketoacids derived from leucine, isoleucine, and valine. The multienzyme complex affected in MSUD, the mitrochondrial branched-chain alpha-ketoacid (BCKD) dehydrogenase complex was purified in 1978 to homogeneity in Reed's laboratory. This led to the later cloning of cDNAs and genes for subunits of the human BCKD complex. Genetic heterogeneity in MSUD is now explained by the various mutations that occur in the E1 alpha, E1 beta, E2, and E3 loci of the BCKD complex. Recently, we found that bacterial chaperonins GroEL and GroES promote folding and assembly of E1 decarboxylase component of the BCKD complex in Escherichia coli. Pulse-chase labeling in this system showed that a subset of E1 alpha mutations, notably the homozygous Y393N-alpha in Mennonite MSUD patients, impedes the assembly of the mutant E1 alpha subunit with normal E1 beta. The assembly defect is associated with a rapid degradation of the normal E1 beta subunit in MSUD cells. Retrovirus-mediated transduction of lymphoblasts from a Mennonite MSUD patient with a normal E1 alpha cDNA resulted in a complete restoration of BCKD activity. This was accompanied by a stabilization of the normal E1 beta subunit through assembly with recombinant E1 alpha. The results demonstrated the feasibility of stable correction of E1 alpha-deficient (type IA) MSUD and provided a basis for the development of gene therapy.
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PMID:Maple syrup urine disease: it has come a long way. 954 32

An isoleucine/valine polymorphism was observed at codon 1464 of the ATP7A gene, which is thought to encode a copper transporting adenosine triphosphatase (ATPase). The frequency of Val1464 was estimated to be 5.7% in the Japanese population. This polymorphism may be useful in genetic studies of Menkes disease.
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PMID:An Ile/Val polymorphism at codon 1464 of the ATP7A gene. 1057 Sep 20

Classical Menkes disease is a neurodegenerative disorder caused by mutations in the copper-transporting ATPase ATP7A gene which, when untreated, is usually fatal in early childhood. A mild form of Menkes disease was originally reported in 1981 and clinical progress of the patient at 10 years described subsequently. The causative mutation is c.4085C>T in exon 21, causing an alanine to valine substitution in the highly conserved TM7 domain at the C-terminal end of the Menkes protein. Here we report his status at 34 years of age. Intellectual impairment is mild. Ataxia has nearly resolved but motor retardation, dysarthria and an extreme slow speech rate remain. In contrast to patients with the occipital horn syndrome, there have been no connective tissue complications of his mild Menkes disease. He has been under long-term copper therapy for more than 30 years and he continues to enjoy a good quality of life.
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PMID:The mild form of menkes disease: a 34 year progress report on the original case. 2343 May 51

Clinical finding of cutis laxa, characterized by wrinkled, redundant, sagging, nonelastic skin, is of growing significance due to its occurrence in several different inborn errors of metabolism (IEM). Metabolic cutis laxa results from Menkes syndrome, caused by a defect in the ATPase copper transporting alpha (ATP7A) gene; congenital disorders of glycosylation due to mutations in subunit 7 of the component of oligomeric Golgi (COG7)-congenital disorders of glycosylation (CDG) complex; combined disorder of N- and O-linked glycosylation, due to mutations in ATPase H+ transporting V0 subunit a2 (ATP6VOA2) gene; pyrroline-5-carboxylate reductase 1 deficiency; pyrroline-5-carboxylate synthase deficiency; macrocephaly, alopecia, cutis laxa, and scoliosis (MACS) syndrome, due to Ras and Rab interactor 2 (RIN2) mutations; transaldolase deficiency caused by mutations in the transaldolase 1 (TALDO1) gene; Gerodermia osteodysplastica due to mutations in the golgin, RAB6-interacting (GORAB or SCYL1BP1) gene; and mitogen-activated pathway (MAP) kinase defects, caused by mutations in several genes [protein tyrosine phosphatase, non-receptor-type 11 (PTPN11), RAF, NF, HRas proto-oncogene, GTPase (HRAS), B-Raf proto-oncogene, serine/threonine kinase (BRAF), MEK1/2, KRAS proto-oncogene, GTPase (KRAS), SOS Ras/Rho guanine nucleotide exchange factor 2 (SOS2), leucine rich repeat scaffold protein (SHOC2), NRAS proto-oncogene, GTPase (NRAS), and Raf-1 proto-oncogene, serine/threonine kinase (RAF1)], which regulate the Ras-MAPK cascade. Here, we further expand the list of inborn errors of metabolism associated with cutis laxa by describing the clinical presentation of a 17-month-old girl with Leigh-like syndrome due to enoyl coenzyme A hydratase, short chain, 1, mitochondria (ECHS1) deficiency, a mitochondrial matrix enzyme that catalyzes the second step of the beta-oxidation spiral of fatty acids and plays an important role in amino acid catabolism, particularly valine.
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PMID:Unique presentation of cutis laxa with Leigh-like syndrome due to ECHS1 deficiency. 2840 71