Frints S G, Schrander-Stumpel C T, Schoenmakers E F, Engelen J J, Reekers A B, Van den Neucker A M, Smeets E, Devlieger H, Fryns J P
Division of Molecular Cell Biology/Genetics, Maastricht University, The Netherlands.
Genet Couns. 1998;9(1):5-14.
We report 3 patients with a 7q terminal deletion. The first, a 7 weeks old female, with a de novo 7q36-->qter deletion, was microcephalic and had a partial hypoplasia of the corpus callosum on the MRI-scan of the brain. The second, a 3 months old male, showed microcephaly, disproportionate growth retardation, truncal obesity and facial dysmorfism giving the clinical impression of a "microcephalic primordial dwarfism (osteodysplastic type)". At the age of 6 months he had developed a single maxillary central incisor suggesting a minimal form of holoprosencephaly (HPE). Additional FISH-studies showed a 7q36.1-->qter deletion, as the unbalanced product of a t(5;7)(q35.2;q36.1)pat. The de novo 7q36-->qter deletion in the third patient, a 5 years old female, was associated with borderline intelligence, mild microcephaly, small midface, choanal narrowing and a single maxillary central incisor as a minimal form of HPE. CT- and MRI-scan of the brain were normal. In these 3 patients extensive FISH analysis was performed to investigate the possible involvement of the HPE gene region on chromosome 7q36. The target gene for HPE, the Sonic hedgehog gene (SHH) as well as several other genes important for normal brain development (En2;HOX1,HTR5A) were found to be deleted in all three patients. Our findings stress the importance of 7q36 microdeletion studies in patients with even minimal signs of HPE, as relative microcephaly with small midface (choanal narrowing), agenesis/hypoplasia of the corpus callosum/septum pellucidum, thalamic fusion or a single maxillary central incisor.
我们报告了3例7号染色体长臂末端缺失的患者。第一例是一名7周大的女性，患有新发的7q36→qter缺失，头小畸形，脑部MRI扫描显示胼胝体部分发育不全。第二例是一名3个月大的男性，表现为头小畸形、生长发育不成比例迟缓、躯干肥胖和面部畸形，临床印象为“头小畸形原始侏儒症（骨发育异常型）”。6个月大时，他长出了一颗上颌中切牙，提示为最轻微形式的前脑无裂畸形（HPE）。额外的荧光原位杂交（FISH）研究显示存在7q36.1→qter缺失，是父源t(5;7)(q35.2;q36.1)不平衡产物。第三例患者是一名5岁女性，新发的7q36→qter缺失与边缘智力、轻度头小畸形、中面部小、后鼻孔狭窄以及作为最轻微形式HPE的一颗上颌中切牙有关。脑部CT和MRI扫描正常。对这3例患者进行了广泛的FISH分析，以研究7号染色体长臂36区HPE基因区域可能受累情况。发现所有3例患者中，HPE的靶基因音猬因子基因（SHH）以及其他几个对正常脑发育重要的基因（En2；HOX1、HTR5A）均缺失。我们的研究结果强调了在即使有最轻微HPE体征的患者中进行7q36微缺失研究的重要性，这些体征包括相对头小畸形伴中面部小（后鼻孔狭窄）、胼胝体/透明隔发育不全/缺失、丘脑融合或一颗上颌中切牙。
