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Identification of a mutation cluster in mevalonate kinase deficiency, including a new mutation in a patient of Mennonite ancestry

Mevalonate kinase (MKase) deficiency (MKD) is a rare autosomal recessive disorder in the pathway of cholesterol and nonsterol isoprenoid biosynthesis. Thus far, two disease-causing missense alleles have been identified, N301T and A334T. We report four additional mutations associated with MKD: L264F,...

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Main Authors: Hinson, Debra D. (Author) , Ross, Richard M. (Author) , Krisans, Skaidrite (Author) , Shaw, Joanne L. (Author) , Kozich, Viktor (Author) , Rolland, Marie-Odile (Author) , Divry, Priscille (Author) , Mancini, Josette (Author) , Hoffmann, Georg F. (Author) , Gibson, K. Michael (Author)
Format: Article (Journal)
Language:English
Published: August 1999
In: The American journal of human genetics
Year: 1999, Volume: 65, Issue: 2, Pages: 327-335
ISSN:1537-6605
DOI:10.1086/302489
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1086/302489
Verlag, lizenzpflichtig, Volltext: https://www.sciencedirect.com/science/article/pii/S0002929707620497
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Author Notes:Debra D. Hinson, Richard M. Ross, Skaidrite Krisans, Joanne L. Shaw, Viktor Kozich, Marie-Odile Rolland, Priscille Divry, Josette Mancini, Georg F. Hoffmann, K. Michael Gibson
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Summary:Mevalonate kinase (MKase) deficiency (MKD) is a rare autosomal recessive disorder in the pathway of cholesterol and nonsterol isoprenoid biosynthesis. Thus far, two disease-causing missense alleles have been identified, N301T and A334T. We report four additional mutations associated with MKD: L264F, T243I, L265P, and I268T, the last found in a patient of Mennonite ancestry. Electrophoretic analysis of bacterially expressed wild-type and mutant MKase indicated that I268T and T243I mutants produced normal or somewhat reduced amounts of MKase protein; conversely, L264F and L265P mutations resulted in considerably decreased, or absent, MKase protein. Immunoblot analysis of MKase from all patients suggested that the MKase polypeptide was grossly intact and produced in amounts comparable to control levels. Three mutations resulted in significantly diminished MKase enzyme activity (<2%), whereas the I268T allele yielded ∼20% residual enzyme activity. Our results should allow more-accurate identification of carriers and indicate a mutation “cluster” within amino acids 240-270 of the mature MKase polypeptide.
Item Description:Online verfügbar: 9. Januar 2008
Gesehen am 26.02.2026
Physical Description:Online Resource
ISSN:1537-6605
DOI:10.1086/302489

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