Topçu M, Gartioux C, Ribierre F, Yalçinkaya C, Tokus E, Oztekin N, Beckmann J S, Ozguc M, Seboun E
Department of Pediatric Neurology, Hacettepe University Hospital and Institute of Neurological Sciences, Sihhiye, Turkey.
Am J Hum Genet. 2000 Feb;66(2):733-9. doi: 10.1086/302758.
The leukodystrophies form a complex group of orphan genetic disorders that primarily affect myelin, the main constituent of the brain white matter. Among the leukodystrophies of undetermined etiology, a new clinical entity called "vacuoliting megalencephalic leukoencephalopathy" (VL) was recently recognized. VL is characterized by diffuse swelling of the white matter, large subcortical cysts, and megalencephaly with infantile onset. Family studies in several ethnic groups have suggested an autosomal recessive mode of inheritance. We mapped the VL gene to chromosome 22qtel, within a 3-cM linkage interval between markers D22S1161 and n66c4 (maximum LOD score 10.12 at recombination fraction.0, for marker n66c4; maximum multipoint LOD score 17 for this interval) by genome scan of 13 Turkish families. Linkage analysis under the genetic-heterogeneity hypothesis showed no genetic heterogeneity. No abnormalities were found in three tested candidate genes (fibulin-1 and glutathione S-transferases 1 and 2).
脑白质营养不良是一组复杂的罕见遗传性疾病，主要影响髓磷脂，而髓磷脂是脑白质的主要成分。在病因不明的脑白质营养不良中，一种名为“空泡性巨脑性白质脑病”（VL）的新临床实体最近被确认。VL的特征是白质弥漫性肿胀、大脑皮质下大囊肿以及婴儿期发病的巨脑症。对多个种族群体的家族研究表明其遗传方式为常染色体隐性遗传。通过对13个土耳其家庭进行基因组扫描，我们将VL基因定位到22号染色体长臂末端，位于标记D22S1161和n66c4之间3厘摩的连锁区间内（标记n66c4在重组率为0时的最大对数优势分数为10.12；该区间的最大多点对数优势分数为17）。在遗传异质性假设下进行的连锁分析显示不存在遗传异质性。在三个经过检测的候选基因（纤连蛋白-1以及谷胱甘肽S-转移酶1和2）中未发现异常。
