PMID- 10480354
OWN - NLM
STAT- MEDLINE
DCOM- 19990923
LR  - 20190722
IS  - 0340-6717 (Print)
IS  - 0340-6717 (Linking)
VI  - 105
IP  - 1-2
DP  - 1999 Jul-Aug
TI  - Mutation analysis of hereditary multiple exostoses in the Chinese.
PG  - 45-50
AB  - Hereditary multiple exostoses (EXT; MIM 133700) is an autosomal dominant bone
      disorder. It is genetically heterogeneous with at least three chromosomal loci:
      EXT1 on 8q24.1, EXT2 on 11p11, and EXT3 on 19p. EXT1 and EXT2, the two genes
      responsible for EXT1 and EXT2, respectively, have been cloned. Recently, three
      other members of the EXT gene family, named the EXT-like genes (EXTL: EXTL1,
      EXTL2, and EXTL3), have been isolated. EXT1, EXT2, and the three EXTLs are
      homologous with one another. We have identified the intron-exon boundaries of
      EXTL1 and EXTL3 and analyzed EXT1, EXT2, EXTL1, and EXTL3, in 36 Chinese families
      with EXT, to identify underlying disease-related mutations in the Chinese
      population. Of the 36 families, five and 12 family groups have mutations in EXT1 
      and EXT2, respectively. No disease-related mutation has been found in either
      EXTL1 or EXTL2, although one polymorphism has been detected in EXTL1. Of the 15
      different mutations (three families share a common mutation in EXT2), 12 are
      novel. Most of the mutations are either frameshift or nonsense mutations (12/15).
      These mutations lead directly or indirectly to premature stop codons, and the
      mutations generate truncated proteins. This finding is consistent with the
      hypothesis that the development of EXT is mainly attributable to loss of gene
      function. Missense mutations are rare in our families, but these mutations may
      reflect some functionally crucial regions of these proteins. EXT1 is the most
      frequent single cause of EXT in the Caucasian population in Europe and North
      America. It accounts for about 40% of cases of EXT. Our study of 36 EXT Chinese
      families has found that EXT1 seems much less common in the Chinese population,
      although the frequency of the EXT2 mutation is similar in the Caucasian and
      Chinese populations. Our findings suggest a possibly different genetic spectrum
      of this disease in different populations.
FAU - Xu, L
AU  - Xu L
AD  - National Laboratory of Medical Genetics, Hunan Medical University, Changsha, PR
      China.
FAU - Xia, J
AU  - Xia J
FAU - Jiang, H
AU  - Jiang H
FAU - Zhou, J
AU  - Zhou J
FAU - Li, H
AU  - Li H
FAU - Wang, D
AU  - Wang D
FAU - Pan, Q
AU  - Pan Q
FAU - Long, Z
AU  - Long Z
FAU - Fan, C
AU  - Fan C
FAU - Deng, H X
AU  - Deng HX
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - Germany
TA  - Hum Genet
JT  - Human genetics
JID - 7613873
RN  - 0 (EXTL3 protein, human)
RN  - 0 (Membrane Proteins)
RN  - 0 (Proteins)
RN  - 0 (Tumor Suppressor Proteins)
RN  - EC 2.4.1.- (EXTL1 protein, human)
RN  - EC 2.4.1.- (EXTL2 protein, human)
RN  - EC 2.4.1.- (N-Acetylglucosaminyltransferases)
RN  - EC 2.4.1.- (N-Acetylhexosaminyltransferases)
RN  - EC 2.4.1.224 (exostosin-1)
RN  - EC 2.4.1.224 (exostosin-2)
SB  - IM
MH  - China
MH  - DNA Mutational Analysis
MH  - Exons
MH  - Exostoses, Multiple Hereditary/*genetics
MH  - Frameshift Mutation
MH  - Humans
MH  - Introns
MH  - *Membrane Proteins
MH  - Models, Genetic
MH  - *Mutation
MH  - Mutation, Missense
MH  - *N-Acetylglucosaminyltransferases
MH  - N-Acetylhexosaminyltransferases/genetics
MH  - Polymorphism, Genetic
MH  - Polymorphism, Single-Stranded Conformational
MH  - Proteins/*genetics
MH  - *Tumor Suppressor Proteins
EDAT- 1999/09/10 00:00
MHDA- 1999/09/10 00:01
CRDT- 1999/09/10 00:00
PHST- 1999/09/10 00:00 [pubmed]
PHST- 1999/09/10 00:01 [medline]
PHST- 1999/09/10 00:00 [entrez]
AID - 10.1007/s004399900058 [doi]
PST - ppublish
SO  - Hum Genet. 1999 Jul-Aug;105(1-2):45-50. doi: 10.1007/s004399900058.