PMID- 10590074
OWN - NLM
STAT- MEDLINE
DCOM- 20000110
LR  - 20220129
IS  - 0006-4971 (Print)
IS  - 0006-4971 (Linking)
VI  - 94
IP  - 12
DP  - 1999 Dec 15
TI  - Mutations in ribosomal protein S19 gene and diamond blackfan anemia: wide
      variations in phenotypic expression.
PG  - 4294-306
AB  - Mutations of the ribosomal protein S19 (RPS19) gene were recently identified in
      10 patients with Diamond Blackfan anemia (DBA). To determine the prevalence of
      mutations in this gene in DBA and to begin to define the molecular basis for the 
      observed variable clinical phenotype of this disorder, the genomic sequence of
      the 6 exons and the 5' untranslated region of the RPS19 gene was directly
      assessed in DBA index cases from 172 new families. Mutations affecting the coding
      sequence of RPS19 or splice sites were found in 34 cases (19.7%), whereas
      mutations in noncoding regions were found in 8 patients (4.6%). Mutations
      included nonsense, missense, splice sites, and frameshift mutations. A hot spot
      for missense mutations was identified between codons 52 and 62 of the RPS19 gene 
      in a new sequence consensus motif
      W-[YFW]-[YF]-x-R-[AT]-A-[SA]-x-[AL]-R-[HRK]-[ILV]-Y. No correlation between the
      nature of mutations and the different patterns of clinical expression, including 
      age at presentation, presence of malformations, and therapeutic outcome, could be
      documented. Moreover, RPS19 mutations were also found in some first-degree
      relatives presenting only with isolated high erythrocyte adenosine deaminase
      activity and/or macrocytosis. The lack of a consistent relationship between the
      nature of the mutations and the clinical phenotype implies that yet unidentified 
      factors modulate the phenotypic expression of the primary genetic defect in
      families with RPS19 mutations.
FAU - Willig, T N
AU  - Willig TN
AD  - Life Science Division, Lawrence Berkeley National Laboratory, Berkeley, CA, USA. 
      tnwillig@lbl.gov
FAU - Draptchinskaia, N
AU  - Draptchinskaia N
FAU - Dianzani, I
AU  - Dianzani I
FAU - Ball, S
AU  - Ball S
FAU - Niemeyer, C
AU  - Niemeyer C
FAU - Ramenghi, U
AU  - Ramenghi U
FAU - Orfali, K
AU  - Orfali K
FAU - Gustavsson, P
AU  - Gustavsson P
FAU - Garelli, E
AU  - Garelli E
FAU - Brusco, A
AU  - Brusco A
FAU - Tiemann, C
AU  - Tiemann C
FAU - Perignon, J L
AU  - Perignon JL
FAU - Bouchier, C
AU  - Bouchier C
FAU - Cicchiello, L
AU  - Cicchiello L
FAU - Dahl, N
AU  - Dahl N
FAU - Mohandas, N
AU  - Mohandas N
FAU - Tchernia, G
AU  - Tchernia G
LA  - eng
GR  - E.0619/TI_/Telethon/Italy
GR  - DK26263/DK/NIDDK NIH HHS/United States
GR  - DK32094/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Blood
JT  - Blood
JID - 7603509
RN  - 0 (Ribosomal Proteins)
RN  - 0 (ribosomal protein S19)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Amino Acid Sequence
MH  - Base Sequence
MH  - Child, Preschool
MH  - Fanconi Anemia/*genetics/physiopathology
MH  - Female
MH  - Humans
MH  - Infant
MH  - Male
MH  - Molecular Sequence Data
MH  - *Mutation
MH  - Pedigree
MH  - Ribosomal Proteins/*genetics
EDAT- 1999/12/10 00:00
MHDA- 1999/12/10 00:01
CRDT- 1999/12/10 00:00
PHST- 1999/12/10 00:00 [pubmed]
PHST- 1999/12/10 00:01 [medline]
PHST- 1999/12/10 00:00 [entrez]
AID - S0006-4971(20)36664-7 [pii]
PST - ppublish
SO  - Blood. 1999 Dec 15;94(12):4294-306.