Twenty-one novel mutations in the GLB1 gene identified in a large group of GM1-gangliosidosis and Morquio B patients: possible common origin for the prevalent p.R59H mutation among gypsies.
Twenty-one novel mutations in the GLB1 gene identified in a large group of GM1-gangliosidosis and Morquio B patients: possible common origin for the prevalent p.R59H mutation among gypsies.
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DOI：
10.1002/humu.9451
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发表时间：
2006-10-01
期刊：
影响因子：
3.9
通讯作者：
Grinberg, Daniel
中科院分区：
文献类型：
--
作者：
Santamaria, Raul;Chabas, Amparo;Grinberg, Daniel
GM1-神经节苷脂贮积症和 Morquio B 病是罕见的溶酶体贮积症，由 GLB1 基因突变导致的 β-半乳糖苷酶缺乏引起。根据发病年龄和症状严重程度，已确定了 GM1-神经节苷脂贮积症的三种主要临床形式：婴儿型、晚期婴儿/青少年型和成人型。我们对 30 名 GM1 神经节苷脂沉积症患者和 5 名 Morquio B 患者（主要是西班牙裔）进行了突变分析，并鉴定了所有致病突变。发现了 30 种不同的突变，其中 21 种是新的。除两名成人和一名青少年患者外，所有 GM1 神经节苷脂沉积症患者均受到婴儿型的影响。为所有患者提供临床结果。我们报告了新突变 p.T420K 和 p.L264S 分别与成年型和幼年型的关联。此外，新突变 p.Y83C 与 Morquio B 病相关。在 30 名 GM1 神经节苷脂沉积症患者中，6 名是吉普赛裔（罗马人）。此外，这六名吉普赛患者不仅具有相同的突变（p.R59H），而且具有共同的单倍型。这一观察结果表明该组中可能存在奠基者效应，并表明 p.R59H 突变的筛查可能适合吉普赛血统的 GM1 神经节苷脂病患者。这是首次对一大群伊比利亚 GM1 神经节苷脂沉积症和 Morquio B 患者进行详尽的突变分析。
GM1-gangliosidosis and Morquio B disease are rare lysosomal storage disorders caused by beta-galactosidase deficiency due to mutations in the GLB1 gene. Three major clinical forms of GM1-gangliosidosis have been established on the basis of age of onset and severity of symptoms: infantile, late infantile/juvenile, and adult. We performed mutation analysis on 30 GM1-gangliosidosis and five Morquio B patients, mainly of Spanish origin, and all the causative mutations were identified. Thirty different mutations were found, 21 of which were novel. With the exception of two adults and one juvenile patient, all the GM1-gangliosidosis patients were affected by the infantile form. Clinical findings are presented for all patients. We report the association of the novel mutations p.T420K and p.L264S with the adult form and the juvenile form, respectively. In addition, the novel mutation p.Y83C was associated with Morquio B disease. Among the 30 GM1-gangliosidosis patients, 6 were of Gypsy origin (Roma). Moreover, those six Gypsy patients shared not only the same mutation (p.R59H) but also a common haplotype. This observation indicates a possible founder effect in this group and suggests that screening of the p.R59H mutation may be appropriate in GM1-gangliosidosis patients of Gypsy origin. This is the first exhaustive mutational analysis performed in a large group of Iberian GM1-gangliosidosis and Morquio B patients.