PMID- 10506123
OWN - NLM
STAT- MEDLINE
DCOM- 19991109
LR  - 20191210
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 274
IP  - 41
DP  - 1999 Oct 8
TI  - Molecular basis for the progeroid variant of Ehlers-Danlos syndrome.
      Identification and characterization of two mutations in galactosyltransferase I
      gene.
PG  - 28841-4
AB  - Progeroid type Ehlers-Danlos (E-D) syndrome was reported to be caused by defects 
      in galactosyltransferase I (EC 2.4.1.133), which is involved in the synthesis of 
      common linkage regions of proteoglycans. Recently, we isolated cDNA of the
      galactosyltransferase I (XGalT-1) (Okajima, T., Yoshida, K., Kondo, T., and
      Furukawa, K. (1999) J. Biol. Chem. 274, 22915-22918). Therefore, we analyzed
      mutations in this gene of a patient with progeroid type E-D syndrome by reverse
      transcription polymerase chain reaction and direct sequencing. Two changes of G
      and T to A and C at 186 and 206, respectively, were detected. Then, we determined
      the genomic DNA sequences encompassing the A186D and L206P mutations, revealing
      that the unaffected parents and two siblings were heterozygous for either one of 
      the two different mutations and normal, while the patient had both of two
      different mutant genes. Enzymatic functions of cDNA clones of XGalT-1 containing 
      the individual mutations were examined, elucidating that L206P clone completely
      lost the activity, while A186D retained approximately 50% or 10% of the activity 
      when analyzed with extracts from cDNA transfectant cells or recombinant soluble
      enzymes, respectively. Moreover, L206P enzyme showed diffuse staining in the
      cytoplasm of transfectant cells, while the wild type or A186D clones showed Golgi
      pattern. These results indicated that the mutations in XGalT-1 were at least one 
      of main molecular basis for progeroid type E-D syndrome.
FAU - Okajima, T
AU  - Okajima T
AD  - Department of Biochemistry II, Nagoya University School of Medicine, Tsurumai,
      Nagoya 466-0065, Japan.
FAU - Fukumoto, S
AU  - Fukumoto S
FAU - Furukawa, K
AU  - Furukawa K
FAU - Urano, T
AU  - Urano T
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - EC 2.4.1.- (Galactosyltransferases)
RN  - EC 2.4.1.133 (xylosylprotein 4-beta-galactosyltransferase)
SB  - IM
MH  - Amino Acid Sequence
MH  - Animals
MH  - CHO Cells
MH  - Cloning, Molecular
MH  - Cricetinae
MH  - DNA Mutational Analysis
MH  - Ehlers-Danlos Syndrome/*genetics
MH  - Fluorescent Antibody Technique
MH  - Galactosyltransferases/chemistry/*genetics
MH  - Heterozygote
MH  - Humans
MH  - L Cells
MH  - Male
MH  - Mice
MH  - Molecular Sequence Data
MH  - Mutation
MH  - Progeria/*genetics
MH  - Sequence Alignment
MH  - Transfection
EDAT- 1999/10/03 00:00
MHDA- 1999/10/03 00:01
CRDT- 1999/10/03 00:00
PHST- 1999/10/03 00:00 [pubmed]
PHST- 1999/10/03 00:01 [medline]
PHST- 1999/10/03 00:00 [entrez]
AID - 10.1074/jbc.274.41.28841 [doi]
PST - ppublish
SO  - J Biol Chem. 1999 Oct 8;274(41):28841-4. doi: 10.1074/jbc.274.41.28841.