PMID- 10533030
OWN - NLM
STAT- MEDLINE
DCOM- 19991130
LR  - 20190905
IS  - 0148-7299 (Print)
IS  - 0148-7299 (Linking)
VI  - 87
IP  - 2
DP  - 1999 Nov 19
TI  - Two distinct phenotypes caused by two different missense mutations in the same
      codon of the VHL gene.
PG  - 163-7
AB  - We have identified a family segregating von Hippel-Lindau (VHL) disease with a
      previously unreported T547A mutation in exon 1 of the VHL gene that causes a
      Tyr112 to Asn missense alteration in the protein. The mutation was identified by 
      nucleotide sequencing and confirmed by restriction enzyme digestion. The mutation
      cosegregated with the disease in all five tested affected individuals from the
      extended family. The family consists of more than 100 at-risk individuals over
      seven generations. To date, we have identified 13 affected individuals of whom
      seven have had renal cell carcinoma and one has had a pheochromocytoma. No other 
      case of a neuroendocrine tumor of the pancreas or adrenal gland
      (pheochromocytoma) was found or recognized retrospectively. Other manifestations 
      in this family include retinal angioma and hemangioblastoma of the central
      nervous system. We also found the T547A mutation in three asymptomatic members of
      the family, ages 12, 19, and 20. Another mutation, T547C, which causes Tyr112 to 
      His, has been seen at the same position and has been associated with VHL type 2A 
      (pheochromocytoma, but no renal cell carcinoma) in two families with a total of
      22 affected individuals [Chen F, Slife L, Kishida T, Mulvihill J, Tisherman SE,
      Zbar B, 1996: J Med Genet 33:716-717]. Thus, different amino acid changes at the 
      same position can cause very distinct clinical phenotypes. It will be interesting
      to elucidate the functional differences that underlie the different phenotypes.
CI  - Copyright 1999 Wiley-Liss, Inc.
FAU - Bradley, J F
AU  - Bradley JF
AD  - Molecular Genetics Laboratory, Sections of Medical Genetics and
      Hematology-Oncology, Children's Mercy Hospital, Kansas City, Missouri 64108, USA.
FAU - Collins, D L
AU  - Collins DL
FAU - Schimke, R N
AU  - Schimke RN
FAU - Parrott, H N
AU  - Parrott HN
FAU - Rothberg, P G
AU  - Rothberg PG
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Am J Med Genet
JT  - American journal of medical genetics
JID - 7708900
RN  - 0 (Codon)
RN  - 0 (Proteins)
RN  - 0 (Tumor Suppressor Proteins)
RN  - EC 2.3.2.27 (Ubiquitin-Protein Ligases)
RN  - EC 2.3.2.27 (Von Hippel-Lindau Tumor Suppressor Protein)
RN  - EC 6.- (Ligases)
RN  - EC 6.3.2.- (VHL protein, human)
SB  - IM
MH  - Adult
MH  - Amino Acid Substitution/genetics
MH  - Base Sequence
MH  - Carcinoma, Renal Cell/genetics
MH  - Child
MH  - Codon/*genetics
MH  - DNA Mutational Analysis
MH  - Exons/genetics
MH  - Female
MH  - Humans
MH  - *Ligases
MH  - Male
MH  - Mutation, Missense/*genetics
MH  - Pedigree
MH  - Phenotype
MH  - Pheochromocytoma/genetics
MH  - Proteins/*genetics
MH  - *Tumor Suppressor Proteins
MH  - *Ubiquitin-Protein Ligases
MH  - Von Hippel-Lindau Tumor Suppressor Protein
MH  - von Hippel-Lindau Disease/*genetics
EDAT- 1999/10/26 00:00
MHDA- 1999/10/26 00:01
CRDT- 1999/10/26 00:00
PHST- 1999/10/26 00:00 [pubmed]
PHST- 1999/10/26 00:01 [medline]
PHST- 1999/10/26 00:00 [entrez]
AID - 10.1002/(SICI)1096-8628(19991119)87:2<163::AID-AJMG7>3.0.CO;2-A [pii]
AID - 10.1002/(sici)1096-8628(19991119)87:2<163::aid-ajmg7>3.0.co;2-a [doi]
PST - ppublish
SO  - Am J Med Genet. 1999 Nov 19;87(2):163-7. doi:
      10.1002/(sici)1096-8628(19991119)87:2<163::aid-ajmg7>3.0.co;2-a.