Pirola B, Bortotto L, Giglio S, Piovan E, Janes A, Guerrini R, Zuffardi O
Biologia Generale e Genetica Medica, Università di Pavia, Italy.
J Med Genet. 1998 Dec;35(12):1031-3. doi: 10.1136/jmg.35.12.1031.
Agenesis of the corpus callosum (ACC) is a relatively common brain abnormality resulting from developmental defects either limited to the structures leading to the proper formation of the corpus callosum or involving the embryo forebrain more generally. ACC is genetically heterogeneous with autosomal dominant, autosomal recessive, and X linked inheritance and has also been reported in subjects with aneuploidies involving several chromosomes. Among them, distal 6q deletions have been consistently reported in association with ACC, suggesting that there is a gene in the deleted region whose haploinsufficiency impairs normal corpus callosum development. We have studied a child with ACC with Probst bundles and a deletion at 6q25 of about 8 cM, from D6S1496 to D6S437. Probst bundles are the axons that should have formed the corpus callosum but, unable to cross the midline owing to absence of the massa commissuralis, they run longitudinally along the medial walls of the lateral ventricles from the frontal to the occipital lobes. Thus, their presence suggests that a gene located in the 6q deleted region is specifically involved in the formation of the massa commissuralis and that its haploinsufficiency leads to primary ACC.
胼胝体发育不全（ACC）是一种相对常见的脑异常，由发育缺陷引起，这些缺陷要么局限于导致胼胝体正常形成的结构，要么更普遍地涉及胚胎前脑。ACC具有遗传异质性，有常染色体显性、常染色体隐性和X连锁遗传，并且在涉及多条染色体非整倍体的个体中也有报道。其中，6q远端缺失一直被报道与ACC相关，这表明缺失区域存在一个基因，其单倍剂量不足会损害胼胝体的正常发育。我们研究了一名患有ACC且伴有普罗布斯特束（Probst bundles）以及6q25约8厘摩（cM）区域（从D6S1496到D6S437）缺失的儿童。普罗布斯特束是本应形成胼胝体的轴突，但由于连合质块缺失而无法穿过中线，它们沿着侧脑室的内侧壁从额叶到枕叶纵向延伸。因此，它们的存在表明位于6q缺失区域的一个基因特别参与连合质块的形成，并且其单倍剂量不足会导致原发性ACC。
