PMID- 10417275
OWN - NLM
STAT- MEDLINE
DCOM- 19990820
LR  - 20200824
IS  - 0002-9297 (Print)
IS  - 1537-6605 (Electronic)
IS  - 0002-9297 (Linking)
VI  - 65
IP  - 2
DP  - 1999 Aug
TI  - Identification of a mutation cluster in mevalonate kinase deficiency, including a 
      new mutation in a patient of Mennonite ancestry.
PG  - 327-35
AB  - 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 approximately 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.
FAU - Hinson, D D
AU  - Hinson DD
AD  - Institute of Metabolic Disease, Baylor University Medical Center, Dallas, TX, 
      USA.
FAU - Ross, R M
AU  - Ross RM
FAU - Krisans, S
AU  - Krisans S
FAU - Shaw, J L
AU  - Shaw JL
FAU - Kozich, V
AU  - Kozich V
FAU - Rolland, M O
AU  - Rolland MO
FAU - Divry, P
AU  - Divry P
FAU - Mancini, J
AU  - Mancini J
FAU - Hoffmann, G F
AU  - Hoffmann GF
FAU - Gibson, K M
AU  - Gibson KM
LA  - eng
SI  - OMIM/251170
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Am J Hum Genet
JT  - American journal of human genetics
JID - 0370475
RN  - 0 (Recombinant Fusion Proteins)
RN  - EC 2.7.1.- (Phosphotransferases (Alcohol Group Acceptor))
RN  - EC 2.7.1.36 (mevalonate kinase)
SB  - IM
MH  - Alleles
MH  - Amino Acid Sequence
MH  - Amino Acid Substitution
MH  - Cells, Cultured
MH  - Christianity
MH  - DNA Mutational Analysis
MH  - Escherichia coli/genetics
MH  - Female
MH  - Fibroblasts/enzymology/metabolism
MH  - Humans
MH  - Lymphocytes/enzymology/metabolism
MH  - Male
MH  - Metabolism, Inborn Errors/enzymology/*genetics
MH  - Molecular Sequence Data
MH  - Mutation/genetics
MH  - Nuclear Family
MH  - Pedigree
MH  - Phosphotransferases (Alcohol Group Acceptor)/*deficiency/*genetics/isolation & 
      purification/metabolism
MH  - Recombinant Fusion Proteins/biosynthesis/genetics/isolation & 
      purification/metabolism
MH  - Sequence Alignment
PMC - PMC1377931
EDAT- 1999/07/27 10:00
MHDA- 2000/03/21 09:00
CRDT- 1999/07/27 10:00
PHST- 1999/07/27 10:00 [pubmed]
PHST- 2000/03/21 09:00 [medline]
PHST- 1999/07/27 10:00 [entrez]
AID - S0002-9297(07)62049-7 [pii]
AID - 10.1086/302489 [doi]
PST - ppublish
SO  - Am J Hum Genet. 1999 Aug;65(2):327-35. doi: 10.1086/302489.