The isochromosome i(7)(q10) carrying c.258+2t>c mutation of the SBDS gene does not promote development of myeloid malignancies in patients with Shwachman syndrome.
Leukemia
; 23(4): 708-11, 2009 Apr.
Article
de En
| MEDLINE
| ID: mdl-19148133
ABSTRACT
Shwachman-Diamond syndrome (SDS) is an autosomal recessive disorder, characterized by exocrine pancreatic insufficiency, skeletal abnormalities and bone marrow (BM) dysfunction with an increased risk to develop myelodysplastic syndrome and/or acute myeloid leukaemia (MDS/AML). SDS is caused, in nearly 90% of cases, by two common mutations (that is, c.183_184TA>CT and c.258+2T>C) in exon 2 of the SBDS gene, localized on chromosome 7. Clonal chromosome anomalies are often found in the BM of SDS patients; the most frequent is an isochromosome for long arms of chromosome 7, i(7)(q10). We studied eight patients with SDS carrying the i(7)(q10) who were compound heterozygotes for SBDS mutations. By assessing the parental origin of the i(7)(q10) using microsatellite analysis, we inferred from the results which mutation was present in double dose in the isochromosome. We demonstrate that in all cases the i(7)(q10) carries a double dose of the c.258+2T>C, and we suggest that, as the c.258+2T>C mutation still allows the production of some amount of normal protein, this may contribute to the low incidence of MDS/AML in this subset of SDS patients.
Texte intégral:
1
Collection:
01-internacional
Base de données:
MEDLINE
Sujet principal:
Syndromes myélodysplasiques
/
Chromosomes humains de la paire 7
/
Protéines
/
Isochromosomes
/
Mutation
Type d'étude:
Etiology_studies
Limites:
Adolescent
/
Adult
/
Child
/
Child, preschool
/
Humans
/
Infant
Langue:
En
Journal:
Leukemia
Sujet du journal:
HEMATOLOGIA
/
NEOPLASIAS
Année:
2009
Type de document:
Article
Pays d'affiliation:
Italie