PMID- 10087994
OWN - NLM
STAT- MEDLINE
DCOM- 19990503
LR  - 20071114
IS  - 1079-9796 (Print)
IS  - 1079-9796 (Linking)
VI  - 24
IP  - 3
DP  - 1998 Sep
TI  - The spectrum of somatic mutations in the PIG-A gene in paroxysmal nocturnal
      hemoglobinuria includes large deletions and small duplications.
PG  - 370-84
AB  - Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired clonal blood disorder
      characterized by chronic hemolysis with hemoglobinuria and venous thrombosis. PNH
      clones arise through somatic mutations in the X-linked PIG-A gene that occur in
      early hematopoietic stem cells. Here we report 28 previously undescribed
      mutations; we confirm that somatic mutations are spread throughout the entire
      coding region of the PIG-A gene and that the majority are frameshift mutations
      producing a non-functional PIG-A protein (PIG-A(o)). In addition, we found 1
      total deletion of the PIG-A gene, and 2 short nucleotide duplications. Although
      mutations are spread throughout the entire coding region, we observe more
      missense mutations in exon 2 than in the other exons. The increasing number of
      identified missense PIG-A mutations should help elucidate structure-function
      relationships in the PIG-A protein.
FAU - Nafa, K
AU  - Nafa K
AD  - Department of Human Genetics, Memorial Sloan Kettering Cancer Center, NY, New
      York 10021, USA. k-nafa@ski.mskcc.org
FAU - Bessler, M
AU  - Bessler M
FAU - Castro-Malaspina, H
AU  - Castro-Malaspina H
FAU - Jhanwar, S
AU  - Jhanwar S
FAU - Luzzatto, L
AU  - Luzzatto L
LA  - eng
GR  - R0I-HL-56778/HL/NHLBI 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 Cells Mol Dis
JT  - Blood cells, molecules & diseases
JID - 9509932
RN  - 0 (Membrane Proteins)
RN  - 0 (phosphatidylinositol glycan-class A protein)
SB  - IM
MH  - DNA Mutational Analysis
MH  - Female
MH  - Frameshift Mutation
MH  - *Gene Duplication
MH  - Hemoglobinuria, Paroxysmal/*genetics
MH  - Humans
MH  - Male
MH  - Membrane Proteins/*genetics
MH  - *Mutation
MH  - Nucleic Acid Hybridization
MH  - Polymorphism, Single-Stranded Conformational
MH  - Sequence Analysis, DNA
MH  - *Sequence Deletion
MH  - X Chromosome/*genetics
EDAT- 1998/10/29 00:00
MHDA- 1998/10/29 00:01
CRDT- 1998/10/29 00:00
PHST- 1998/10/29 00:00 [pubmed]
PHST- 1998/10/29 00:01 [medline]
PHST- 1998/10/29 00:00 [entrez]
AID - S1079-9796(98)90203-0 [pii]
AID - 10.1006/bcmd.1998.0203 [doi]
PST - ppublish
SO  - Blood Cells Mol Dis. 1998 Sep;24(3):370-84. doi: 10.1006/bcmd.1998.0203.