PMID- 10364516
OWN - NLM
STAT- MEDLINE
DCOM- 19990805
LR  - 20200824
IS  - 0002-9297 (Print)
IS  - 0002-9297 (Linking)
VI  - 65
IP  - 1
DP  - 1999 Jul
TI  - X-linked dyskeratosis congenita is predominantly caused by missense mutations in 
      the DKC1 gene.
PG  - 50-8
AB  - Dyskeratosis congenita is a rare inherited bone marrow-failure syndrome
      characterized by abnormal skin pigmentation, nail dystrophy, and mucosal
      leukoplakia. More than 80% of patients develop bone-marrow failure, and this is
      the major cause of premature death. The X-linked form of the disease (MIM 305000)
      has been shown to be caused by mutations in the DKC1 gene. The gene encodes a
      514-amino-acid protein, dyskerin, that is homologous to Saccharomyces cerevisiae 
      Cbf5p and rat Nap57 proteins. By analogy to the homologues in other species,
      dyskerin is predicted to be a nucleolar protein with a role in both the
      biogenesis of ribosomes and, in particular, the pseudouridylation of rRNA
      precursors. We have determined the genomic structure of the DKC1 gene; it
      consists of 15 exons spanning a region of 15 kb. This has enabled us to screen
      for mutations in the genomic DNA, by using SSCP analysis. Mutations were detected
      in 21 of 37 additional families with dyskeratosis congenita that were analyzed.
      These mutations consisted of 11 different single-nucleotide substitutions, which 
      resulted in 10 missense mutations and 1 putative splicing mutation within an
      intron. The missense change A353V was observed in 10 different families and was
      shown to be a recurring de novo event. Two polymorphisms were also detected, one 
      of which resulted in the insertion of an additional lysine in the
      carboxy-terminal polylysine domain. It is apparent that X-linked dyskeratosis
      congenita is predominantly caused by missense mutations; the precise effect on
      the function of dyskerin remains to be determined.
FAU - Knight, S W
AU  - Knight SW
AD  - Department of Haematology, Imperial College School of Medicine, Hammersmith
      Hospital, London, United Kingdom.
FAU - Heiss, N S
AU  - Heiss NS
FAU - Vulliamy, T J
AU  - Vulliamy TJ
FAU - Greschner, S
AU  - Greschner S
FAU - Stavrides, G
AU  - Stavrides G
FAU - Pai, G S
AU  - Pai GS
FAU - Lestringant, G
AU  - Lestringant G
FAU - Varma, N
AU  - Varma N
FAU - Mason, P J
AU  - Mason PJ
FAU - Dokal, I
AU  - Dokal I
FAU - Poustka, A
AU  - Poustka A
LA  - eng
SI  - GENBANK/AJ010395
SI  - GENBANK/AJ010396
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 (Cell Cycle Proteins)
RN  - 0 (DKC1 protein, human)
RN  - 0 (Microtubule-Associated Proteins)
RN  - 0 (Nuclear Proteins)
RN  - 0 (RNA-Binding Proteins)
RN  - 0 (Ribonucleoproteins, Small Nuclear)
RN  - 0 (Saccharomyces cerevisiae Proteins)
RN  - EC 4.2.1.- (Hydro-Lyases)
RN  - EC 4.2.1.70 (CBF5 protein, S cerevisiae)
SB  - IM
MH  - Amino Acid Sequence
MH  - Cell Cycle Proteins/chemistry/*genetics
MH  - Dyskeratosis Congenita/*genetics
MH  - Female
MH  - Humans
MH  - *Hydro-Lyases
MH  - Male
MH  - Microtubule-Associated Proteins/chemistry
MH  - Models, Genetic
MH  - Molecular Sequence Data
MH  - *Mutation, Missense
MH  - Nuclear Proteins/chemistry/*genetics
MH  - Pedigree
MH  - Polymorphism, Genetic
MH  - Polymorphism, Single-Stranded Conformational
MH  - RNA-Binding Proteins/chemistry
MH  - *Ribonucleoproteins, Small Nuclear
MH  - *Saccharomyces cerevisiae Proteins
MH  - Sequence Homology, Amino Acid
MH  - *X Chromosome
PMC - PMC1378074
EDAT- 1999/06/12 10:00
MHDA- 2000/03/21 09:00
CRDT- 1999/06/12 10:00
PHST- 1999/06/12 10:00 [pubmed]
PHST- 2000/03/21 09:00 [medline]
PHST- 1999/06/12 10:00 [entrez]
AID - S0002-9297(07)63727-6 [pii]
AID - 10.1086/302446 [doi]
PST - ppublish
SO  - Am J Hum Genet. 1999 Jul;65(1):50-8. doi: 10.1086/302446.