Three new BLM gene mutations associated with Bloom syndrome.
Bloom's syndrome (BS) is a rare autosomal recessive disease predisposing patients to all types of cancers affecting the general population. BS cells display a high level of genetic instability, including a 10-fold increase in the rate of sister chromatid exchanges, currently the only objective criterion for BS diagnosis. We have developed a method for screening the BLM gene for mutations based on direct genomic DNA sequencing. A questionnaire based on clinical information, cytogenetic features, and family history was addressed to physicians prescribing BS genetic screening, with the aim of confirming or guiding diagnosis. We report here four BLM gene mutations, three of which have not been described before. Three of the mutations are frameshift mutations, and the fourth is a nonsense mutation. All these mutations introduce a stop codon, and may therefore be considered to have deleterious biological effect. This approach should make it possible to identify new mutations and to correlate them with clinical information.
Amor-Guéret
Mounira
M
Institut Curie, Centre de Recherche, Orsay, France. mounira.amor@curie.u-psud.fr
Dubois-d'Enghien
Catherine
C
Laugé
Anthony
A
Onclercq-Delic
Rosine
R
Barakat
Abdelhamid
A
Chadli
Elbekkay
E
Bousfiha
Ahmed Aziz
AA
Benjelloun
Meriem
M
Flori
Elisabeth
E
Doray
Bérénice
B
Laugel
Vincent
V
Lourenço
Maria Teresa
MT
Gonçalves
Rui
R
Sousa
Silvia
S
Couturier
Jérôme
J
Stoppa-Lyonnet
Dominique
D
D000328:Adult; D001816:Bloom Syndrome / Q000175:diagnosis* / Q000235:genetics* / Q000503:physiopathology; D002648:Child; D002675:Child, Preschool; D018389:Codon, Nonsense; D004265:DNA Helicases / Q000235:genetics*; D004252:DNA Mutational Analysis / Q000379:methods*; D005260:Female; D016368:Frameshift Mutation; D005820:Genetic Testing; D016678:Genome; D006801:Humans; D007223:Infant; D008297:Male; D009154:Mutation; D053484:RecQ Helicases; D017422:Sequence Analysis, DNA
D018389:Codon, Nonsense; C097151:Bloom syndrome protein; D004265:DNA Helicases; D053484:RecQ Helicases