Sirotkin H, Morrow B, DasGupta R, Goldberg R, Patanjali S R, Shi G, Cannizzaro L, Shprintzen R, Weissman S M, Kucherlapati R
Department of Molecular Genetics, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
Hum Mol Genet. 1996 May;5(5):617-24. doi: 10.1093/hmg/5.5.617.
Velo-cardio-facial syndrome (VCFS) and DiGeorge syndrome (DGS) are developmental disorders characterized by a spectrum of phenotypes including velopharyngeal insufficiency, conotruncal heart defects and facial dysmorphology among others. Eighty to eighty-five percent of VCFS/DGS patients are hemizygous for a portion of chromosome 22. It is likely that the genes encoded by this region play a role in the etiology of the phenotypes associated with the disorders. Using a cDNA selection protocol, we isolated a novel clathrin heavy chain cDNA (CLTD) from the VCFS/DGS minimally deleted interval. The cDNA encodes a protein of 1638 amino acids. CLTD shares significant homology, but is not identical to the ubiquitously expressed clathrin heavy chain gene. The CLTD gene also shows a unique pattern of expression, having its maximal level of expression in skeletal muscle. Velopharyngeal insufficiency and muscle weakness are common features of VCFS patients. Based on the location and expression pattern of CLTD, we suggest hemizygosity at this locus may play a role in the etiology of one of the VCFS-associated phenotypes.
腭心面综合征（VCFS）和迪格奥尔格综合征（DGS）是发育障碍疾病，其特征为一系列表型，包括腭咽闭合不全、圆锥动脉干心脏缺陷和面部畸形等。80%至85%的VCFS/DGS患者22号染色体的一部分存在半合子状态。该区域编码的基因可能在与这些疾病相关的表型病因中起作用。我们使用一种cDNA筛选方案，从VCFS/DGS最小缺失区间分离出一个新的网格蛋白重链cDNA（CLTD）。该cDNA编码一种含1638个氨基酸的蛋白质。CLTD具有显著的同源性，但与普遍表达的网格蛋白重链基因并不相同。CLTD基因还表现出独特的表达模式，在骨骼肌中表达水平最高。腭咽闭合不全和肌肉无力是VCFS患者的常见特征。基于CLTD的定位和表达模式，我们认为该基因座的半合子状态可能在一种与VCFS相关的表型病因中起作用。
