Grossi Serena, Regis Stefano, Rosano Camillo, Corsolini Fabio, Uziel Graziella, Sessa Maria, Di Rocco Maja, Parenti Giancarlo, Deodato Federica, Leuzzi Vincenzo, Biancheri Roberta, Filocamo Mirella
Laboratorio Diagnosi Pre-Postnatale Malattie Metaboliche, Genova, Italy.
Hum Mutat. 2008 Nov;29(11):E220-30. doi: 10.1002/humu.20851.
Metachromatic leukodystrophy (MLD), the demyelinating disorder resulting from impaired sulfatide catabolism, is caused by allelic mutations of the Arylsulfatase A (ARSA) locus except for extremely rare cases of Saposin-B (Sap-B) deficiency. We characterized twenty-one unrelated Italian patients among which seventeen were due to ARSA activity deficiency and 4 others resulted from Saposin-B defect. Overall, we found 20 different mutant ARSA alleles and 2 different Sap-B alleles. The eleven new ARSA alleles (c.53C>A; c.88G>C; c.372G>A; c.409_411delCCC; c.634G>C; [c.650G>A;c.1108C>T]; c.845A>G; c.906G>C; c.919G>T; c.1102-3C>G; c.1126T>A) were functionally characterized and the novel amino acid changes were also modelled into the three-dimensional structure. The present study is aimed at providing a broader picture of the molecular basis of MLD in the Italian population. It also emphasizes the importance of a comprehensive evaluation in MLD diagnosis including biochemical, enzymatic and molecular investigations.
异染性脑白质营养不良（MLD）是一种因硫脂分解代谢受损导致的脱髓鞘疾病，除极罕见的鞘脂激活蛋白B（Sap - B）缺乏病例外，均由芳基硫酸酯酶A（ARSA）基因座的等位基因突变引起。我们对21名无亲缘关系的意大利患者进行了特征分析，其中17名是由于ARSA活性缺乏，另外4名是由鞘脂激活蛋白B缺陷导致的。总体而言，我们发现了20种不同的突变ARSA等位基因和2种不同的鞘脂激活蛋白B等位基因。对11种新的ARSA等位基因（c.53C>A；c.88G>C；c.372G>A；c.409_411delCCC；c.634G>C；[c.650G>A；c.1108C>T]；c.845A>G；c.906G>C；c.919G>T；c.1102 - 3C>G；c.1126T>A）进行了功能特征分析，并将新的氨基酸变化也构建到三维结构中。本研究旨在更全面地了解意大利人群中MLD的分子基础。它还强调了在MLD诊断中进行综合评估的重要性，包括生化、酶学和分子研究。
