title: Three new BLM gene mutations associated with Bloom syndrome.
abstract: 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.
authors.affiliation: Institut Curie, Centre de Recherche, Orsay, France. mounira.amor@curie.u-psud.fr
authors.forename: Mounira
authors.initials: M
authors.lastname: Amor-Guéret
authors.forename: Catherine
authors.initials: C
authors.lastname: Dubois-d'Enghien
authors.forename: Anthony
authors.initials: A
authors.lastname: Laugé
authors.forename: Rosine
authors.initials: R
authors.lastname: Onclercq-Delic
authors.forename: Abdelhamid
authors.initials: A
authors.lastname: Barakat
authors.forename: Elbekkay
authors.initials: E
authors.lastname: Chadli
authors.forename: Ahmed Aziz
authors.initials: AA
authors.lastname: Bousfiha
authors.forename: Meriem
authors.initials: M
authors.lastname: Benjelloun
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Flori
authors.forename: Bérénice
authors.initials: B
authors.lastname: Doray
authors.forename: Vincent
authors.initials: V
authors.lastname: Laugel
authors.forename: Maria Teresa
authors.initials: MT
authors.lastname: Lourenço
authors.forename: Rui
authors.initials: R
authors.lastname: Gonçalves
authors.forename: Silvia
authors.initials: S
authors.lastname: Sousa
authors.forename: Jérôme
authors.initials: J
authors.lastname: Couturier
authors.forename: Dominique
authors.initials: D
authors.lastname: Stoppa-Lyonnet
mesh_terms: 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
chemical_list: D018389:Codon, Nonsense; C097151:Bloom syndrome protein; D004265:DNA Helicases; D053484:RecQ Helicases