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A comparison of the mutation spectra of Menkes disease and Wilson disease.
Hum Genet. 2004 Jan; 114(2):165-72.HG

Abstract

The genes for two copper-transporting ATPases, ATP7A and ATP7B, are defective in the heritable disorders of copper imbalance, Menkes disease (MNK) and Wilson disease (WND), respectively. A comparison of the two proteins shows extensive conservation in the signature domains, with amino acid identities outside of the conserved domains being limited. The mutation spectra of MNK and WND were compared to confirm and refine further regions critical for normal function. Mutations were found to be relatively widespread; however, the majority was concentrated within defined functional domains and membrane-spanning segments, reinforcing the importance of these regions for protein function. Of the total published point mutations in ATP7A, 23.0% are splice-site, 20.7% nonsense, 17.2% missense, and 39.1% small insertions/deletions. There is a high prevalence (58.2%) of missense mutations in ATP7B. For the other mutations in ATP7B, 7.4% are splice-site, 7.4% nonsense, and 27.0% small insertions/deletions. A region of possible importance is the intervening sequence between the last copper-binding domain and the first transmembrane helix, as this region has a high percentage of MNK mutations. Similarly, the region containing the ATP-binding domain has 24.6% of all WND mutations. The study of mutation locations is useful for defining critical regions or residues and for efficient molecular diagnosis.

Authors+Show Affiliations

Department of Medical Genetics, 8-39 Medical Sciences Building, University of Alberta, Edmonton, Alberta T6G 2H7, Canada.No affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

14579150

Citation

Hsi, Gloria, and Diane W. Cox. "A Comparison of the Mutation Spectra of Menkes Disease and Wilson Disease." Human Genetics, vol. 114, no. 2, 2004, pp. 165-72.
Hsi G, Cox DW. A comparison of the mutation spectra of Menkes disease and Wilson disease. Hum Genet. 2004;114(2):165-72.
Hsi, G., & Cox, D. W. (2004). A comparison of the mutation spectra of Menkes disease and Wilson disease. Human Genetics, 114(2), 165-72.
Hsi G, Cox DW. A Comparison of the Mutation Spectra of Menkes Disease and Wilson Disease. Hum Genet. 2004;114(2):165-72. PubMed PMID: 14579150.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - A comparison of the mutation spectra of Menkes disease and Wilson disease. AU - Hsi,Gloria, AU - Cox,Diane W, Y1 - 2003/10/25/ PY - 2003/05/29/received PY - 2003/09/22/accepted PY - 2003/10/28/pubmed PY - 2004/4/13/medline PY - 2003/10/28/entrez SP - 165 EP - 72 JF - Human genetics JO - Hum Genet VL - 114 IS - 2 N2 - The genes for two copper-transporting ATPases, ATP7A and ATP7B, are defective in the heritable disorders of copper imbalance, Menkes disease (MNK) and Wilson disease (WND), respectively. A comparison of the two proteins shows extensive conservation in the signature domains, with amino acid identities outside of the conserved domains being limited. The mutation spectra of MNK and WND were compared to confirm and refine further regions critical for normal function. Mutations were found to be relatively widespread; however, the majority was concentrated within defined functional domains and membrane-spanning segments, reinforcing the importance of these regions for protein function. Of the total published point mutations in ATP7A, 23.0% are splice-site, 20.7% nonsense, 17.2% missense, and 39.1% small insertions/deletions. There is a high prevalence (58.2%) of missense mutations in ATP7B. For the other mutations in ATP7B, 7.4% are splice-site, 7.4% nonsense, and 27.0% small insertions/deletions. A region of possible importance is the intervening sequence between the last copper-binding domain and the first transmembrane helix, as this region has a high percentage of MNK mutations. Similarly, the region containing the ATP-binding domain has 24.6% of all WND mutations. The study of mutation locations is useful for defining critical regions or residues and for efficient molecular diagnosis. SN - 0340-6717 UR - https://www.unboundmedicine.com/medline/citation/14579150/A_comparison_of_the_mutation_spectra_of_Menkes_disease_and_Wilson_disease_ L2 - https://dx.doi.org/10.1007/s00439-003-1045-y DB - PRIME DP - Unbound Medicine ER -