Galactosialidosis: review and analysis of CTSA gene mutations.
Galactosialidosis: review and analysis of CTSA gene mutations.
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DOI：
10.1186/1750-1172-8-114
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发表时间：
2013-08-02
影响因子：
3.7
通讯作者：
Morrone A
中科院分区：
文献类型：
--
作者：
Caciotti A;Catarzi S;Tonin R;Lugli L;Perez CR;Michelakakis H;Mavridou I;Donati MA;Guerrini R;d'Azzo A;Morrone A
编码保护性蛋白/组织蛋白酶A或PPCA的CTSA基因的突变导致β-半乳糖苷酶（GLB1）和神经氨酸酶1 （NEU1）的继发性缺乏，导致溶酶体储存障碍半乳糖胞苷病（GS）。文献中很少报道GS的临床病例，大多数属于青少年/成年组患者。通过分析GenBank数据库中可用的三种PPCA/CTSA亚型，讨论了该基因突变的正确命名。表型-基因型相关性已通过计算分析和回顾先前报道的单氨基酸取代进行评估。我们报告了4例罕见的婴儿型GS的临床和突变分析。我们发现了三个新的核苷酸变化，其中两个导致错义突变，C . 347a >G (p.His116Arg), C . 775t >C (p.Cys259Arg)，第三个，C . 1216c >T，导致p.Gln406*停止密码子，这是一种首次在GS中发现的突变。c.114delG突变的意大利奠基人效应可以根据本文和文献中报道的携带该突变的仅有三名患者的起源提出。在早期的报道中，突变命名是根据所有CTSA同种异构体（三种不同的同种异构体）来选择的，因此产生了很多混乱。为了帮助医生解释检测到的突变，我们标记了CTSA突变的正确命名法。本文讨论了由CTSA的多功能引起的病理复杂性，以及与CTSA基因长度相关的非常低的突变数量（总共只有23个）。此外，所有报告的错义突变的计算机功能预测使我们能够密切预测婴儿早期，婴儿晚期和少年表型，也揭示了少年表型的不同严重程度。
Mutations in the CTSA gene, that encodes the protective protein/cathepsin A or PPCA, lead to the secondary deficiency of β-galactosidase (GLB1) and neuraminidase 1 (NEU1), causing the lysosomal storage disorder galactosialidosis (GS). Few clinical cases of GS have been reported in the literature, the majority of them belonging to the juvenile/adult group of patients. The correct nomenclature of mutations for this gene is discussed through the analysis of the three PPCA/CTSA isoforms available in the GenBank database. Phenotype-genotype correlation has been assessed by computational analysis and review of previously reported single amino acid substitutions. We report the clinical and mutational analyses of four cases with the rare infantile form of GS. We identified three novel nucleotide changes, two of them resulting in the missense mutations, c.347A>G (p.His116Arg), c.775T>C (p.Cys259Arg), and the third, c.1216C>T, resulting in the p.Gln406* stop codon, a type of mutation identified for the first time in GS. An Italian founder effect of the c.114delG mutation can be suggested according to the origin of the only three patients carrying this mutation reported here and in the literature. In early reports mutations nomenclature was selected according to all CTSA isoforms (three different isoforms), thus generating a lot of confusion. In order to assist physicians in the interpretation of detected mutations, we mark the correct nomenclature for CTSA mutations. The complexity of pathology caused by the multifunctions of CTSA, and the very low numbers of mutations (only 23 overall) in relation to the length of the CTSA gene are discussed. In addition, the in silico functional predictions of all reported missense mutations allowed us to closely predict the early infantile, late infantile and juvenile phenotypes, also disclosing different degrees of severity in the juvenile phenotype.
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影响因子：
4.4
作者：
Vacic, Vladimir;Oldfield, Christopher J.;Dunker, A. Keith
通讯作者：
Dunker, A. Keith
DOI：
10.1073/pnas.79.15.4535
发表时间：
1982-01-01
期刊：
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA-BIOLOGICAL SCIENCES
影响因子：
--
作者：
DAZZO, A;HOOGEVEEN, A;GALJAARD, H
通讯作者：
GALJAARD, H
影响因子：
11.4
作者：
Cuervo, AM;Mann, L;Dice, JF
通讯作者：
Dice, JF
影响因子：
0.8
作者：
Durante, Alessandro;Traini, Mariaemilia;Spoladore, Roberto
通讯作者：
Spoladore, Roberto
影响因子：
15.9
作者：
SHIMMOTO, M;FUKUHARA, Y;SUZUKI, Y
通讯作者：
SUZUKI, Y