Mutations in the PIG-A gene causing paroxysmal nocturnal hemoglobinuria are mainly of the frameshift type.
Blood
; 86(12): 4650-5, 1995 Dec 15.
Article
in En
| MEDLINE
| ID: mdl-8541557
ABSTRACT
Paroxysmal nocturnal hemoglobinuria is an acquired hemolytic anemia associated with somatic mutations in the X-linked gene PIG-A, which encodes a protein involved in the biosynthesis of glycosyl phosphatidylinositol anchors. To further elucidate the molecular basis of paroxysmal nocturnal hemoglobinuria, we have worked out a systematic and relatively rapid methodology to scan for mutations in the entire coding region of the PIG-A gene. By this methodology, we have identified 15 different somatic mutations in 12 patients. The mutations were spread throughout the entire PIG-A-coding region. Of the mutations, 10 caused frameshifts, 6 caused small deletions, 3 caused small insertions, and 1 caused deletion-insertion. Five single base pair substitutions caused three missense mutations, one nonsense mutation, and one defect in the donor splice site of intron 4. In each of 3 patients, two independent mutations were identified. The predominance of frameshift mutations may reflect selection for somatic mutations giving rise to clones with a completely nonfunctional PIG-A protein.
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Collection:
01-internacional
Database:
MEDLINE
Main subject:
Frameshift Mutation
/
Hemoglobinuria, Paroxysmal
/
Membrane Proteins
Limits:
Female
/
Humans
/
Male
Language:
En
Journal:
Blood
Year:
1995
Document type:
Article
Affiliation country:
Reino Unido