menkes kinky hair syndrome

Summary

Summary: An inherited disorder of copper metabolism transmitted as an X-linked trait and characterized by the infantile onset of HYPOTHERMIA, feeding difficulties, hypotonia, SEIZURES, bony deformities, pili torti (twisted hair), and severely impaired intellectual development. Defective copper transport across plasma and endoplasmic reticulum membranes results in copper being unavailable for the synthesis of several copper containing enzymes, including PROTEIN-LYSINE 6-OXIDASE; CERULOPLASMIN; and SUPEROXIDE DISMUTASE. Pathologic changes include defects in arterial elastin, neuronal loss, and gliosis. (From Menkes, Textbook of Child Neurology, 5th ed, p125)

Top Publications

  1. Wang Y, Zhu S, Weisman G, Gitlin J, Petris M. Conditional knockout of the Menkes disease copper transporter demonstrates its critical role in embryogenesis. PLoS ONE. 2012;7:e43039 pubmed publisher
    ..These studies demonstrate the essential role of the Atp7a gene in mouse embryonic development and establish a powerful model for understanding the tissue-specific roles of ATP7A in copper metabolism and disease. ..
  2. Gu Y, Kodama H, Murata Y, Mochizuki D, Yanagawa Y, Ushijima H, et al. ATP7A gene mutations in 16 patients with Menkes disease and a patient with occipital horn syndrome. Am J Med Genet. 2001;99:217-22 pubmed
    ..DNA sequencing analysis of the exons and 5'-upstream region of the ATP7A gene in 20 normal individuals and the 19 affected males identified 25 polymorphisms. ..
  3. Tumer Z, Birk Møller L, Horn N. Screening of 383 unrelated patients affected with Menkes disease and finding of 57 gross deletions in ATP7A. Hum Mutat. 2003;22:457-64 pubmed
    ..9% of the Menkes disease patients. Except for a few cases, gross gene deletions result in the classical form of Menkes disease with death in early childhood. ..
  4. Bissig K, Wunderli Ye H, Duda P, Solioz M. Structure-function analysis of purified Enterococcus hirae CopB copper ATPase: effect of Menkes/Wilson disease mutation homologues. Biochem J. 2001;357:217-23 pubmed
    ..Our results reveal that Cys-396 and His-480 of CopB are key residues for ATPase function, and similar roles are suggested for Cys-1000 and His-1069 of Menkes and Wilson ATPases respectively. ..
  5. Kodama H, Sato E, Yanagawa Y, Ozawa H, Kozuma T. Biochemical indicator for evaluation of connective tissue abnormalities in Menkes' disease. J Pediatr. 2003;142:726-8 pubmed
    ..The urinary deoxypyridinoline level was significantly low in the patients with Menkes' disease, indicating that it is a good marker of lysyl oxidase activity, which is related to the connective tissue abnormalities. ..
  6. Voskoboinik I, Camakaris J. Menkes copper-translocating P-type ATPase (ATP7A): biochemical and cell biology properties, and role in Menkes disease. J Bioenerg Biomembr. 2002;34:363-71 pubmed
    ..The effect of these mutations on the catalytic cycle and the cell biology of the Menkes protein, as well as predictions of the effect of particular mutant MNKs on observed Menkes disease symptoms will also be discussed. ..
  7. Vulpe C, Levinson B, Whitney S, Packman S, Gitschier J. Isolation of a candidate gene for Menkes disease and evidence that it encodes a copper-transporting ATPase. Nat Genet. 1993;3:7-13 pubmed
    ..The gene is transcribed in all cell types tested except liver, consistent with the expression of the Menkes defect. ..
  8. Kodama H, Sato E, Gu Y, Shiga K, Fujisawa C, Kozuma T. Effect of copper and diethyldithiocarbamate combination therapy on the macular mouse, an animal model of Menkes disease. J Inherit Metab Dis. 2005;28:971-8 pubmed
  9. Das S, Levinson B, Whitney S, Vulpe C, Packman S, Gitschier J. Diverse mutations in patients with Menkes disease often lead to exon skipping. Am J Hum Genet. 1994;55:883-9 pubmed
    ..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. ..

More Information

Publications76

  1. Qian Y, Tiffany Castiglioni E, Welsh J, Harris E. Copper efflux from murine microvascular cells requires expression of the menkes disease Cu-ATPase. J Nutr. 1998;128:1276-82 pubmed
    ..This study provides strong evidence that a Cu-ATPase in the BBB controls the penetration of Cu into the brain and that lesions to the Cu-ATPase in CVE cells are a primary cause of low brain Cu levels in Menkes disease. ..
  2. Kennerson M, Nicholson G, Kaler S, Kowalski B, Mercer J, Tang J, et al. Missense mutations in the copper transporter gene ATP7A cause X-linked distal hereditary motor neuropathy. Am J Hum Genet. 2010;86:343-52 pubmed publisher
    ..This previously unrecognized genotype-phenotype correlation suggests an important role of the ATP7A copper transporter in motor-neuron maintenance and function. ..
  3. Kaler S. ATP7A-related copper transport diseases-emerging concepts and future trends. Nat Rev Neurol. 2011;7:15-29 pubmed publisher
    ..Collectively, these insights refine our knowledge of the neurology of ATP7A-related copper transport diseases and pave the way for further progress in understanding ATP7A function. ..
  4. Gourdon P, Liu X, Skjørringe T, Morth J, Møller L, Pedersen B, et al. Crystal structure of a copper-transporting PIB-type ATPase. Nature. 2011;475:59-64 pubmed publisher
    ..The structure also provides a framework to analyse missense mutations in the human ATP7A and ATP7B proteins associated with Menkes' and Wilson's diseases. ..
  5. Møller L, Tumer Z, Lund C, Petersen C, Cole T, Hanusch R, et al. Similar splice-site mutations of the ATP7A gene lead to different phenotypes: classical Menkes disease or occipital horn syndrome. Am J Hum Genet. 2000;66:1211-20 pubmed
    ..These findings indicate that the presence of barely detectable amounts of correctly spliced ATP7A transcript is sufficient to permit the development of the milder OHS phenotype, as opposed to classic MD. ..
  6. Bacopoulou F, Henderson L, Philip S. Menkes disease mimicking non-accidental injury. Arch Dis Child. 2006;91:919 pubmed
  7. Watanabe A, Shimizu N. Identification of three novel mutations in Japanese patients with Menkes disease and mutation screening by denaturing high performance liquid chromatography. Pediatr Int. 2005;47:1-6 pubmed
    ..In this study, a mutation analysis in Japanese patients with Menkes disease was performed, as was a mutation screening by denaturing high performance liquid chromatography (DHPLC)...
  8. Qi M, Byers P. Constitutive skipping of alternatively spliced exon 10 in the ATP7A gene abolishes Golgi localization of the menkes protein and produces the occipital horn syndrome. Hum Mol Genet. 1998;7:465-9 pubmed
    ..These findings indicate that endoplasmic reticulum localization only of a variant ATP7A protein is insufficient to effect normal copper transport...
  9. Kirodian B, Gogtay N, Udani V, Kshirsagar N. Treatment of Menkes disease with parenteral copper histidine. Indian Pediatr. 2002;39:183-5 pubmed
  10. Bull P, Thomas G, Rommens J, Forbes J, Cox D. The Wilson disease gene is a putative copper transporting P-type ATPase similar to the Menkes gene. Nat Genet. 1993;5:327-37 pubmed
    ..Two WD patients were found to be homozygous for a seven base deletion within the coding region of Wc1. Wc1 is proposed as the gene for WD...
  11. Mercer J, Grimes A, Ambrosini L, Lockhart P, Paynter J, Dierick H, et al. Mutations in the murine homologue of the Menkes gene in dappled and blotchy mice. Nat Genet. 1994;6:374-8 pubmed
    ..Tissues of the blotchy mouse contained two larger sizes of MNK mRNA demonstrating a likely defect in RNA splicing. Thus, the mottled locus is homologous to the human MNK locus and dappled and blotchy are allelic mutations in this gene...
  12. Kaler S, Gallo L, Proud V, Percy A, Mark Y, Segal N, et al. Occipital horn syndrome and a mild Menkes phenotype associated with splice site mutations at the MNK locus. Nat Genet. 1994;8:195-202 pubmed
    ..In both mutations, maintenance of some normal splicing is demonstrable by RT-PCR, cDNA sequencing and ribonuclease protection...
  13. Gu Y, Kodama H, Sato E, Mochizuki D, Yanagawa Y, Takayanagi M, et al. Prenatal diagnosis of Menkes disease by genetic analysis and copper measurement. Brain Dev. 2002;24:715-8 pubmed
    ..As his early treatment with parenteral copper-histidine prevented the neurological disorders effectively, prenatal diagnosis is very important...
  14. Lenartowicz M, Sasuła K, Zawadowska B. Alterations in kidney morphology in mice with mosaic mutation. Folia Histochem Cytobiol. 2001;39:275-81 pubmed
    ..Pathological changes were observed in the cortex and in the medulla of the kidneys in both groups of mutants and control males injected with cupric chloride (50 microg of CuCl2 per each individual)...
  15. Mercer J, Livingston J, Hall B, Paynter J, Begy C, Chandrasekharappa S, et al. Isolation of a partial candidate gene for Menkes disease by positional cloning. Nat Genet. 1993;3:20-5 pubmed
    ..Partial sequence of the cDNA shows a unique open reading frame containing putative metal binding motifs which have been found in heavy metal resistance genes in bacteria. This gene is a strong candidate for the Menkes disease gene...
  16. Sheela S, Latha M, Liu P, Lem K, Kaler S. Copper-replacement treatment for symptomatic Menkes disease: ethical considerations. Clin Genet. 2005;68:278-83 pubmed
    ..The ethical issues encountered in providing possibly futile treatment in this difficult disorder seem relevant to other pediatric medical conditions as well...
  17. Yamaguchi Y, Heiny M, Suzuki M, Gitlin J. Biochemical characterization and intracellular localization of the Menkes disease protein. Proc Natl Acad Sci U S A. 1996;93:14030-5 pubmed
  18. Tumer Z, Lund C, Tolshave J, Vural B, Tønnesen T, Horn N. Identification of point mutations in 41 unrelated patients affected with Menkes disease. Am J Hum Genet. 1997;60:63-71 pubmed
    ..The present findings not only help us in understanding the underlying genetic defect but are invaluable data especially for carrier detection and prenatal diagnosis of this lethal disorder...
  19. Bahi Buisson N, Kaminska A, Nabbout R, Barnerias C, Desguerre I, de Lonlay P, et al. Epilepsy in Menkes disease: analysis of clinical stages. Epilepsia. 2006;47:380-6 pubmed
    ..Epilepsy is one of the main features of Menkes disease (MD), although it is not described in depth. To determine the spectrum of epilepsy, we studied its main characteristics...
  20. Grange D, Kaler S, Albers G, Petterchak J, Thorpe C, Demello D. Severe bilateral panlobular emphysema and pulmonary arterial hypoplasia: unusual manifestations of Menkes disease. Am J Med Genet A. 2005;139A:151-5 pubmed
  21. Kim B, Smith K, Petris M. A copper treatable Menkes disease mutation associated with defective trafficking of a functional Menkes copper ATPase. J Med Genet. 2003;40:290-5 pubmed
  22. De Bie P, Muller P, Wijmenga C, Klomp L. Molecular pathogenesis of Wilson and Menkes disease: correlation of mutations with molecular defects and disease phenotypes. J Med Genet. 2007;44:673-88 pubmed
    ..As both disorders are characterised by an extensive clinical heterogeneity, we will discus how the underlying genetic defects correlate with the molecular functions of ATP7A and ATP7B and with the clinical expression of these disorders...
  23. La Fontaine S, Mercer J. Trafficking of the copper-ATPases, ATP7A and ATP7B: role in copper homeostasis. Arch Biochem Biophys. 2007;463:149-67 pubmed
  24. Tumer Z, Møller L. Menkes disease. Eur J Hum Genet. 2010;18:511-8 pubmed publisher
    ..Severely affected MD patients die usually before the third year of life. A cure for the disease does not exist, but very early copper-histidine treatment may correct some of the neurological symptoms...
  25. Gu Y, Kodama H, Shiga K, Nakata S, Yanagawa Y, Ozawa H. A survey of Japanese patients with Menkes disease from 1990 to 2003: incidence and early signs before typical symptomatic onset, pointing the way to earlier diagnosis. J Inherit Metab Dis. 2005;28:473-8 pubmed
    ..We also found that many signs had been noted before the patient was brought to a hospital with typical symptoms. These signs may be a clue to early diagnosis of MNK...
  26. Kodama H, Meguro Y, Abe T, Rayner M, Suzuki K, Kobayashi S, et al. Genetic expression of Menkes disease in cultured astrocytes of the macular mouse. J Inherit Metab Dis. 1991;14:896-901 pubmed
    ..These results show that the underlying genetic defect of the macular mouse is expressed in the astrocytes. A similar situation may exist in Menkes disease and cause a failure of copper transport to neurones...
  27. Schlief M, Craig A, Gitlin J. NMDA receptor activation mediates copper homeostasis in hippocampal neurons. J Neurosci. 2005;25:239-46 pubmed
  28. Møller L, Bukrinsky J, Mølgaard A, Paulsen M, Lund C, Tumer Z, et al. Identification and analysis of 21 novel disease-causing amino acid substitutions in the conserved part of ATP7A. Hum Mutat. 2005;26:84-93 pubmed
    ..These findings suggest that although a disease-causing mutation may indicate a functional significance of the affected residue, this is not always the case...
  29. Grimes A, Hearn C, Lockhart P, Newgreen D, Mercer J. Molecular basis of the brindled mouse mutant (Mo(br)): a murine model of Menkes disease. Hum Mol Genet. 1997;6:1037-42 pubmed
    ..In the kidney, immunohistochemistry demonstrated Mnk in the proximal and distal tubules, the distribution is identical in mutant and normal. This distribution is consistent with Mnk being involved in copper resorption from the urine...
  30. Petris M, Mercer J, Culvenor J, Lockhart P, Gleeson P, Camakaris J. Ligand-regulated transport of the Menkes copper P-type ATPase efflux pump from the Golgi apparatus to the plasma membrane: a novel mechanism of regulated trafficking. EMBO J. 1996;15:6084-95 pubmed
  31. Sazinsky M, Mandal A, ARGUELLO J, Rosenzweig A. Structure of the ATP binding domain from the Archaeoglobus fulgidus Cu+-ATPase. J Biol Chem. 2006;281:11161-6 pubmed
    ..Finally, the CopA ATPBD structure provides a basis for understanding the likely structural and functional effects of various mutations that lead to Wilson and Menkes diseases...
  32. Francis M, Jones E, Levy E, Ponnambalam S, Chelly J, Monaco A. A Golgi localization signal identified in the Menkes recombinant protein. Hum Mol Genet. 1998;7:1245-52 pubmed
    ..Therefore, the protein sequence encoded by exon 10 may be responsible for this differential localization and both isoforms may be required for comprehensive transport of copper within the cell...
  33. Ozawa H, Kodama H, Kawaguchi H, Mochizuki T, Kobayashi M, Igarashi T. Renal function in patients with Menkes disease. Eur J Pediatr. 2003;162:51-2 pubmed
  34. Sirleto P, Surace C, Santos H, Bertini E, Tomaiuolo A, Lombardo A, et al. Lyonization effects of the t(X;16) translocation on the phenotypic expression in a rare female with Menkes disease. Pediatr Res. 2009;65:347-51 pubmed publisher
  35. Donsante A, Tang J, Godwin S, Holmes C, Goldstein D, Bassuk A, et al. Differences in ATP7A gene expression underlie intrafamilial variability in Menkes disease/occipital horn syndrome. J Med Genet. 2007;44:492-7 pubmed
    ..We report two unrelated families featuring affected members with unusually disparate clinical and biochemical phenotypes and explore the underlying molecular mechanisms...
  36. Kim B, Smith K, Meagher C, Petris M. A conditional mutation affecting localization of the Menkes disease copper ATPase. Suppression by copper supplementation. J Biol Chem. 2002;277:44079-84 pubmed
    ..Our findings provide a molecular framework for understanding how mutations that affect the proper folding of the MNK transporter in Menkes patients may be responsive to parenteral copper therapy...
  37. Petris M, Strausak D, Mercer J. The Menkes copper transporter is required for the activation of tyrosinase. Hum Mol Genet. 2000;9:2845-51 pubmed
    ..This study also contributes to our understanding of the molecular basis of pigmentation in mammalian cells...
  38. Matsuo M, Tasaki R, Kodama H, Hamasaki Y. Screening for Menkes disease using the urine HVA/VMA ratio. J Inherit Metab Dis. 2005;28:89-93 pubmed
    ..Urine HVA/VMA ratios ranged from 4.1 to 69.7 among 15 patients with Menkes disease, whereas only 0.18% of controls had ratios greater than 4.0. Thus, the urine HVA/VMA ratio is a useful screening method for Menkes disease...
  39. Reed V, Boyd Y. Mutation analysis provides additional proof that mottled is the mouse homologue of Menkes' disease. Hum Mol Genet. 1997;6:417-23 pubmed
    ..Thus we provide further proof that mottled mutants will provide excellent models for MD as well as OHS...
  40. Poulsen L, Horn N, Heilstrup H, Lund C, Tumer Z, Møller L. X-linked recessive Menkes disease: identification of partial gene deletions in affected males. Clin Genet. 2002;62:449-57 pubmed
    ..We demonstrate characterization of partial gene deletions in five patients, and in three of these we were able to determine the breakpoint sequences...
  41. Kodama H, Murata Y. Molecular genetics and pathophysiology of Menkes disease. Pediatr Int. 1999;41:430-5 pubmed
    ..Thus, the objective in treatment of Menkes disease and occipital horn syndrome is to deliver copper to the intracellular compartments where cuproenzymes are synthesized...
  42. Kodama H, Murata Y, Kobayashi M. Clinical manifestations and treatment of Menkes disease and its variants. Pediatr Int. 1999;41:423-9 pubmed
    ..Moreover, early treatment cannot improve non-neurological problems, such as connective tissue laxity. Therefore, alternative therapies for Menkes disease and occipital horn syndrome should be studied...
  43. Murata Y, Kodama H, Mori Y, Kobayashi M, Abe T. Mottled gene expression and copper distribution in the macular mouse, an animal model for Menkes disease. J Inherit Metab Dis. 1998;21:199-202 pubmed
  44. Kodama H, Fujisawa C, Bhadhprasit W. Inherited copper transport disorders: biochemical mechanisms, diagnosis, and treatment. Curr Drug Metab. 2012;13:237-50 pubmed
    ..Patients with Wilson's disease may be at risk of developing hepatocellular carcinoma. Understanding the link between Wilson's disease and hepatocellular carcinoma will be beneficial for disease treatment and prevention...
  45. Kaler S, Tang J, Donsante A, Kaneski C. Translational read-through of a nonsense mutation in ATP7A impacts treatment outcome in Menkes disease. Ann Neurol. 2009;65:108-13 pubmed publisher
  46. Suzuki Kurasaki M, Okabe M, Kurasaki M. Copper-metallothionein in the kidney of macular mice: a model for Menkes disease. J Histochem Cytochem. 1997;45:1493-501 pubmed
    ..We also compared the histochemical localization of Cu-MT in Macular mice and Long-Evans cinnamon rats, a model for Wilson's disease. The significance of this comparison is discussed...
  47. Agertt F, Crippa A, Lorenzoni P, Scola R, Bruck I, Paola L, et al. Menkes' disease: case report. Arq Neuropsiquiatr. 2007;65:157-60 pubmed
    ..The clinical, laboratorial, genetic, muscle biopsy and neurophysiological findings in Menkes disease are discussed...
  48. Lalioti V, Muruais G, Tsuchiya Y, Pulido D, Sandoval I. Molecular mechanisms of copper homeostasis. Front Biosci (Landmark Ed). 2009;14:4878-903 pubmed
    ..In mammalians liver is the major captor, distributor and excreter of Cu. Mutations in the P-type ATPases that interfere with their functioning and traffic are cause of the life-threatening Wilson (ATP7B) and Menkes (ATP7A) diseases...
  49. Lenartowicz M, Starzyński R, Wieczerzak K, Krzeptowski W, Lipiński P, Styrna J. Alterations in the expression of the Atp7a gene in the early postnatal development of the mosaic mutant mice (Atp7a mo-ms) - An animal model for Menkes disease. Gene Expr Patterns. 2011;11:41-7 pubmed publisher
    ..We speculate that disturbance in the expression of the Atp7a gene and, consequently, change in the copper concentration of the organs, may contribute to the early fatal outcome of mosaic males...
  50. Kodama H, Fujisawa C, Bhadhprasit W. Pathology, clinical features and treatments of congenital copper metabolic disorders--focus on neurologic aspects. Brain Dev. 2011;33:243-51 pubmed publisher
    ..Neurologic worsening in patients treated with tetrathiomolybdate has been reported to be lower than rates of neurologic worsening when treating with other chelating agents...
  51. Xu G, Yamano T, Shimada M. Copper distribution in fetus and placenta of the macular mutant mouse as a model of Menkes kinky hair disease. Biol Neonate. 1994;66:302-10 pubmed
    ..The others showed no copper deposit in both the placenta and liver, thus indicating that the former were hemizygous for the mutation and the latter were normal littermates.(ABSTRACT TRUNCATED AT 250 WORDS)..
  52. Levinson B, Packman S, Gitschier J. Deletion of the promoter region in the Atp7a gene of the mottled dappled mouse. Nat Genet. 1997;16:224-5 pubmed
  53. Tang J, Robertson S, Lem K, Godwin S, Kaler S. Functional copper transport explains neurologic sparing in occipital horn syndrome. Genet Med. 2006;8:711-8 pubmed
    ..Our objective was to characterize a novel occipital horn syndrome mutation (N1304S) not associated with aberrant splicing and to determine whether functional copper transport was associated with this allele...
  54. Tumer Z, Møller L, Horn N. Mutation spectrum of ATP7A, the gene defective in Menkes disease. Adv Exp Med Biol. 1999;448:83-95 pubmed
    ..The mutations will be compared briefly with those described in the animal model mottled mouse, and in Wilson disease, the autosomal recessive disorder of copper metabolism...
  55. Packman S, Palmiter R, Karin M, O TOOLE C. Metallothionein messenger RNA regulation in the mottled mouse and Menkes kinky hair syndrome. J Clin Invest. 1987;79:1338-42 pubmed
    b>Menkes kinky hair syndrome is an X-linked neurodegenerative disorder, causing tissue-specific increases in copper and metallothionein content. A mouse model is provided by hemizygotes for mutant alleles at the X-linked mottled locus...
  56. Desai V, Donsante A, Swoboda K, Martensen M, Thompson J, Kaler S. Favorably skewed X-inactivation accounts for neurological sparing in female carriers of Menkes disease. Clin Genet. 2011;79:176-82 pubmed publisher
  57. Yamaguchi Y, Heiny M, Gitlin J. Isolation and characterization of a human liver cDNA as a candidate gene for Wilson disease. Biochem Biophys Res Commun. 1993;197:271-7 pubmed
    ..These data suggest that this cDNA is a candidate gene for Wilson disease and that the protein encoded at this locus is a member of the P-type ATPase family...
  58. Møller L, Mogensen M, Horn N. Molecular diagnosis of Menkes disease: genotype-phenotype correlation. Biochimie. 2009;91:1273-7 pubmed publisher
    ..A clear phenotype-genotype correlation is however difficult to establish, clearly illustrated by the presence of inter- and even intra-familial variability...
  59. Kaler S, Holmes C, Goldstein D, Tang J, Godwin S, Donsante A, et al. Neonatal diagnosis and treatment of Menkes disease. N Engl J Med. 2008;358:605-14 pubmed publisher
  60. Murata Y, Kodama H, Abe T, Ishida N, Nishimura M, Levinson B, et al. Mutation analysis and expression of the mottled gene in the macular mouse model of Menkes disease. Pediatr Res. 1997;42:436-42 pubmed
    ..The distribution of expression of mottled is correlated with cells and tissues showing histopathology or abnormal copper sequestration in macular and other mutants...
  61. Mototani Y, Miyoshi I, Okamura T, Moriya T, Meng Y, Yuan Pei X, et al. Phenotypic and genetic characterization of the Atp7a(Mo-Tohm) mottled mouse: a new murine model of Menkes disease. Genomics. 2006;87:191-9 pubmed
    ..This mutant mouse is the most severe model of human Menkes disease in mottled mice established to date and one of the useful models for understanding the gene function of Menkes disease...
  62. Tanzi R, Petrukhin K, Chernov I, Pellequer J, Wasco W, Ross B, et al. The Wilson disease gene is a copper transporting ATPase with homology to the Menkes disease gene. Nat Genet. 1993;5:344-50 pubmed
  63. Lenartowicz M, Windak R, Tylko G, Kowal M, Styrna J. Effects of copper supplementation on the structure and content of elements in kidneys of mosaic mutant mice. Biol Trace Elem Res. 2010;136:204-20 pubmed publisher
    ..We suggest that copper excess may impair the activity of Na(+)/K(+) ATP-ase in renal tubules of ms/- males. The content of Mg, P, and Cl in kidneys in mutants was also changed after copper administration...
  64. Kaler S, Liew C, Donsante A, Hicks J, Sato S, Greenfield J. Molecular correlates of epilepsy in early diagnosed and treated Menkes disease. J Inherit Metab Dis. 2010;33:583-9 pubmed publisher
    ..Subjects with ATP7A mutations that retain some function seem particularly well protected by early intervention against the possibility of epilepsy...
  65. Chelly J, Tumer Z, Tønnesen T, Petterson A, Ishikawa Brush Y, Tommerup N, et al. Isolation of a candidate gene for Menkes disease that encodes a potential heavy metal binding protein. Nat Genet. 1993;3:14-9 pubmed
    ..These findings should lead to more accurate prenatal diagnosis of this severe disease and a better understanding of the cellular homeostasis of essential heavy metals...
  66. Madsen E, Morcos P, Mendelsohn B, Gitlin J. In vivo correction of a Menkes disease model using antisense oligonucleotides. Proc Natl Acad Sci U S A. 2008;105:3909-14 pubmed publisher
  67. Kodama H, Abe T, Takama M, Takahashi I, Kodama M, Nishimura M. Histochemical localization of copper in the intestine and kidney of macular mice: light and electron microscopic study. J Histochem Cytochem. 1993;41:1529-35 pubmed
    ..These findings indicate that Cu is concentrated in the organelle-free cytoplasm of the affected cells of macular mice. This suggests that the Menkes' mutation affects Cu transport from the cytosol to the organelles in the cell...