Joutel A, Ducros A, Alamowitch S, Cruaud C, Domenga V, Maréchal E, Vahedi K, Chabriat H, Bousser M G, Tournier-Lasserve E
INSERM U25, Paris, France.
Genomics. 1996 Dec 1;38(2):192-8. doi: 10.1006/geno.1996.0615.
CADASIL, a recently identified autosomal dominant condition characterized by the recurrence of subcortical infarcts leading to dementia, was previously mapped to chromosome 19p13.1 within a 2-cM interval, D19S226-D19S199. No recombination event was observed with D19S841, a highly polymorphic microsatellite marker isolated from a cosmid mapped to this region. We recently identified within this cosmid a conserved sequence that we used to screen a fetal brain cDNA library and isolated an ubiquitous and abundantly transcribed gene. We did not detect any mutation of this gene in CADASIL patients, suggesting that it is not implicated in this disorder. Interestingly, this gene encodes a putative protein homologous to several thiamine pyrophosphate-binding proteins previously identified in bacteria, yeast, and plants. The proteins with the highest degree of similarity were the acetolactate synthase enzymes which, in prokaryotes, are involved in the branched chain amino acid biosynthetic pathway, raising fascinating questions on the yet unknown function of this gene in mammals.
伴有皮质下梗死和白质脑病的常染色体显性遗传性脑动脉病（CADASIL）是一种最近才被确认的常染色体显性疾病，其特征是皮质下梗死反复发作并导致痴呆，此前已被定位到19号染色体短臂1区3带（19p13.1）的一个2厘摩（cM）区间内，即D19S226 - D19S199。从定位到该区域的一个黏粒中分离出的高度多态性微卫星标记D19S841，未观察到重组事件。我们最近在这个黏粒中鉴定出一个保守序列，并用它筛选胎儿脑cDNA文库，分离出一个广泛存在且转录丰富的基因。我们在CADASIL患者中未检测到该基因的任何突变，这表明它与这种疾病无关。有趣的是，该基因编码一种推定的蛋白质，与先前在细菌、酵母和植物中鉴定出的几种硫胺焦磷酸结合蛋白同源。相似度最高的蛋白质是乙酰乳酸合酶，在原核生物中，它参与支链氨基酸生物合成途径，这就引发了关于该基因在哺乳动物中尚未明确的功能的有趣问题。
