PMID- 10215410
OWN - NLM
STAT- MEDLINE
DCOM- 19990420
LR  - 20220331
IS  - 1059-7794 (Print)
IS  - 1059-7794 (Linking)
VI  - 11
IP  - 4
DP  - 1998
TI  - A novel missense mutation Ile538Val in the fibroblast growth factor receptor 3 in
      hypochondroplasia. Mutations in brief no. 122. Online.
PG  - 333
AB  - Hypochondroplasia and achondroplasia are skeletal dysplasias, characterized by
      autosomal dominant inheritance and disproportionate short stature, which occurs
      mainly due to growth failure of the extremities. Both dysplasias have been mapped
      to fibroblast growth factor receptor 3 (FGFR3) gene. For hypochondroplasia, two
      point mutations, both responsible for the Asn540Lys substitution in the region
      coding the tyrosine kinase domain have been reported. Here we report an A to G
      transition at position 1651, predicting an Ile538Val substitution in the FGFR3,
      in hypochondroplasia. The substitution is found in a swedish family with three
      affected members. The criteria for hypochondroplasia were disproportionate short 
      stature and radiological evidence of shortened long bones and decrease or absence
      of normal increase in interpedicular distances of the lumbar column. The mutation
      was detected by direct sequencing and restriction enzyme Tai I digestion. The
      base change was not found in the FGFR3 genes of unaffected members of the family 
      nor in seventy-five unrelated unaffected individuals, suggesting that it was not 
      a polymorphism. The Ile538Val substitution is a conservative amino acid change (a
      hydrophobic amino acid incorporated for another hydrophobic amino acid).
      Nevertheless, it is located in the stretch of nine amino acids, which is highly
      conserved among all the human fibroblast growth factor receptors. Considering the
      location of this substitution and the segregation with the phenotype in this
      family, we propose that it is a causative mutation of hypochondroplasia. It is
      difficult to establish whether the Ile538Val substitution is rare in
      hypochondroplasia patients or whether the individuals, who have a moderate degree
      of short stature, rarely seek medical help for the short stature and consequently
      are rarely diagnosed as affected by hypochondroplasia.
FAU - Grigelioniene, G
AU  - Grigelioniene G
AD  - Paediatric Endocrinology Unit, Karolinska Hospital, Stockham, Sweden.
      giedre.grigelioniene@kbh.ki.se
FAU - Hagenas, L
AU  - Hagenas L
FAU - Eklof, O
AU  - Eklof O
FAU - Neumeyer, L
AU  - Neumeyer L
FAU - Haereid, P E
AU  - Haereid PE
FAU - Anvret, M
AU  - Anvret M
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Hum Mutat
JT  - Human mutation
JID - 9215429
RN  - 0 (Receptors, Fibroblast Growth Factor)
RN  - 04Y7590D77 (Isoleucine)
RN  - EC 2.7.10.1 (FGFR3 protein, human)
RN  - EC 2.7.10.1 (Protein-Tyrosine Kinases)
RN  - EC 2.7.10.1 (Receptor, Fibroblast Growth Factor, Type 3)
RN  - HG18B9YRS7 (Valine)
SB  - IM
MH  - Achondroplasia/*genetics
MH  - Amino Acid Sequence
MH  - Amino Acid Substitution/genetics
MH  - Conserved Sequence
MH  - Humans
MH  - Isoleucine/*genetics
MH  - Molecular Sequence Data
MH  - Mutation, Missense/*genetics
MH  - Phenotype
MH  - *Protein-Tyrosine Kinases
MH  - Receptor, Fibroblast Growth Factor, Type 3
MH  - Receptors, Fibroblast Growth Factor/*genetics
MH  - Valine/*genetics
EDAT- 1999/04/24 02:14
MHDA- 2000/06/22 10:00
CRDT- 1999/04/24 02:14
PHST- 1999/04/24 02:14 [pubmed]
PHST- 2000/06/22 10:00 [medline]
PHST- 1999/04/24 02:14 [entrez]
AID - 10.1002/(SICI)1098-1004(1998)11:4<333::AID-HUMU17>3.0.CO;2-J [pii]
AID - 10.1002/(SICI)1098-1004(1998)11:4<333::AID-HUMU18>3.0.CO;2-G [doi]
PST - ppublish
SO  - Hum Mutat. 1998;11(4):333. doi:
      10.1002/(SICI)1098-1004(1998)11:4<333::AID-HUMU18>3.0.CO;2-G.