Daw S C, Taylor C, Kraman M, Call K, Mao J, Schuffenhauer S, Meitinger T, Lipson T, Goodship J, Scambler P
Molecular Medicine Unit, Institute of Child Health, London, UK.
Nat Genet. 1996 Aug;13(4):458-60. doi: 10.1038/ng0896-458.
DiGeorge (DGS, MIM 188400) and velocardiofacial (VCFS, MIM 192430) syndromes may present many clinical problems including cardiac defects, hypoparathyroidism, T-cell immunodeficiency and facial dysmorphism. They are frequently associated with deletions within 22q11.2, but a number of cases have no detectable molecular defect of this region. A number of single case reports with deletions of 10p suggest genetic heterogeneity of DGS. Here we compare the regions of hemizygosity in four patients with terminal deletions of 10p (one patient diagnosed as having hypoparathyroidism and three as DGS) and one patient with a large interstitial deletion (diagnosed as VCFS). Fluorescence in situ hybridization (FISH) analysis demonstrates that these patients have overlapping deletions at the 10p13/10p14 boundary. A YAC contig spanning the shortest region of deletion overlap (SRO) has been assembled, and allows the size of SRO to be approximated to 2 Mb. As with deletions of 22q11, phenotypes vary considerably between affected patients. These results strongly support the hypothesis that haploinsufficiency of a gene or genes within 10p (the DGSII locus) can cause the DGS/VCFS spectrum of malformation.
迪格奥尔格综合征（DGS，MIM 188400）和腭心面综合征（VCFS，MIM 192430）可能会引发许多临床问题，包括心脏缺陷、甲状旁腺功能减退、T细胞免疫缺陷和面部畸形。它们常与22q11.2区域的缺失相关，但也有许多病例在该区域未检测到分子缺陷。一些关于10p缺失的单病例报告提示迪格奥尔格综合征存在基因异质性。在此，我们比较了4例10p末端缺失患者（1例诊断为甲状旁腺功能减退，3例诊断为迪格奥尔格综合征）和1例大片段中间缺失患者（诊断为腭心面综合征）的半合子区域。荧光原位杂交（FISH）分析表明，这些患者在10p13/10p14边界存在重叠缺失。已构建了一个跨越缺失重叠最短区域（SRO）的酵母人工染色体（YAC）重叠群，据此可将SRO的大小估算为2 Mb。与22q11缺失一样，受影响患者的表型差异很大。这些结果有力地支持了这样一种假说，即10p（迪格奥尔格综合征II型基因座）内一个或多个基因的单倍剂量不足可导致迪格奥尔格综合征/腭心面综合征谱系的畸形。
