Ten novel Diamond-Blackfan anemia mutations and three polymorphisms within the rps19 gene.
BACKGROUND
A total of 25% of patients presenting with Diamond-Blackfan anemia (DBA) carry mutations in the rps19 gene, which encodes protein RPS19 of the small ribosomal subunit. The other DBA cases carry mutations in other, unknown gene(s).


METHODS
We searched mutations in 48 DBA families or isolated patients based on PCR of exons of the rps19 gene and automatic sequencing. We also studied three novel intronic polymorphisms in 85 persons (most of the patients and their relatives, when the latter could be investigated).


RESULTS
We identified 10 new mutations within the rps19 gene. We found no obvious correlation between the clinical expression and the nature of the mutation. Besides, we found three polymorphisms within the rps19 gene. Polymorphisms a, b and c were (i) a one-base insertion (+c at position +79) in intron 2, (ii) the g-->c substitution at position +89 also in intron 2 and (iii) the g-->a substitution at position +14 in intron 4. Inheritance studies showed that the polymorphisms were transmitted en bloc, thus defining the --- haplotypes (changes absent) and the +++ haplotypes (changes present). The percentages of each haplotype were about 50% in families and isolated persons with DBA, as well as in controls.


CONCLUSIONS
For the 10 novel mutations found in the rps19 gene, there were no obvious genotype-phenotype correlations. The transmission of the polymorphisms was en bloc and the studies did not suggest any clinical correlates at this stage.
Service d'Hématologie, d'Immunlogie et de Cytogénétique, Hôpital de Bicêtre, AP-HP, Faculté de Médecine Paris-Sud, France.
Alexis
A
Proust
Lydie
L
Da Costa
Patricia
P
Rince
Anaely
A
Landois
Hannah
H
Tamary
Rina
R
Zaizov
Gil
G
Tchernia
Jean
J
Delaunay
D029503:Anemia, Diamond-Blackfan / Q000235:genetics*; D004252:DNA Mutational Analysis; D005091:Exons; D005192:Family Health; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007438:Introns; D009154:Mutation; D010375:Pedigree; D010641:Phenotype; D011110:Polymorphism, Genetic; D012269:Ribosomal Proteins / Q000235:genetics*
D012269:Ribosomal Proteins; C040343:ribosomal protein S19