Clinical and Molecular-Cytogenctic Evaluation of a Family With Partial Jacobsen Syndrome Without Thrombocytopenia Caused by an ∼5 Mb Deletion del(11)(q24.3)

Clinical manifestations of Jacobsen syndrome (JBS) depend on the size of the 11qter deletion, which usually varies between similar to 7 and 20 Mb. Typical JBS features include development delay/mental retardation, short stature, congential heart defects, thrombocytopenia, and characteristic dysmorphic facial features. We report on a family in which a 4-year-old girl as well as her mother and maternal uncle present with subtle features of JBS. Notably, neither thrombocytopenia nor congential anomalies were detected in this family. Cytogenetic analyses revealed normal karyo-types. Using fluorescence in situ hybridization (FISH) and whole-genome oligonucleotide array CGH analyses, we identified an similar to 5 Mb deletion of the terminal part of chromosome 11q in all the three affected family members. The deletion breakpoint was mapped between 129,511,419 and 129,519,794 bp. This is the smallest deletion reported in a JBS patient. Interestingly, the FLI1 (friend leukemia virus integration 1) hematopoiesis factor gene located similar to 6.5 Mb from 11qter and usually deleted in patients with JBS, is intact. Our data support previous hypotheses that FLI1 haploinsufficiency is responsible for thrombocytopenia in patients with JBS. (c) 2008 Wiley-Liss, Inc.