Bernaciak Joanna, Szczałuba Krzysztof, Derwińska Katarzyna, Wiśniowiecka-Kowalnik Barbara, Bocian Ewa, Sasiadek Maria Małgorzata, Makowska Izabela, Stankiewicz Paweł, Smigiel Robert
Department of Medical Genetics, Institute of Mother and Child, Warsaw, Poland.
Am J Med Genet A. 2008 Oct 1;146A(19):2449-54. doi: 10.1002/ajmg.a.32490.
Clinical manifestations of Jacobsen syndrome (JBS) depend on the size of the 11qter deletion, which usually varies between approximately 7 and 20 Mb. Typical JBS features include developmental delay/mental retardation, short stature, congenital 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 congenital anomalies were detected in this family. Cytogenetic analyses revealed normal karyotypes. Using fluorescence in situ hybridization (FISH) and whole-genome oligonucleotide array CGH analyses, we identified an approximately 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 approximately 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.
雅各布森综合征（JBS）的临床表现取决于11q末端缺失的大小，其通常在约7至20兆碱基之间变化。典型的JBS特征包括发育迟缓/智力障碍、身材矮小、先天性心脏缺陷、血小板减少以及特征性的面部畸形特征。我们报告了一个家庭，其中一名4岁女孩以及她的母亲和舅舅表现出JBS的细微特征。值得注意的是，该家庭中未检测到血小板减少或先天性异常。细胞遗传学分析显示核型正常。使用荧光原位杂交（FISH）和全基因组寡核苷酸阵列比较基因组杂交（CGH）分析，我们在所有三名受影响的家庭成员中鉴定出11号染色体q末端约5兆碱基的缺失。缺失断点定位于129,511,419和129,519,794碱基对之间。这是JBS患者中报道的最小缺失。有趣的是，位于距11q末端约6.5兆碱基处且通常在JBS患者中缺失的FLI1（Friend白血病病毒整合1）造血因子基因是完整的。我们的数据支持先前的假设，即FLI1单倍体不足是JBS患者血小板减少的原因。
