黏多糖贮积症Ⅳ A型患者GALNS基因突变的研究进展

doi:10.3969/j.issn.1004-616x.2022.04.012

摘要/Abstract

摘要： 黏多糖贮积症Ⅳ A型是一种由N-乙酰半乳糖胺-6-硫酸酯酶(GALNS)缺乏引起的常染色体隐性遗传病。基因突变导致GALNS缺陷使6-硫酸软骨素和硫酸角蛋白两种黏多糖在溶酶体内聚集，引起溶酶体功能障碍并破坏细胞功能。对疾病的早期准确诊断是优化患者管理的关键，可以显著提高患者生活质量，延长生存时间。然而，黏多糖贮积症Ⅳ A型患者的临床特征与其他疾病重叠，GALNS突变多种多样，且临床表型各有不同，因此黏多糖贮积症Ⅳ A型患者的早期诊断十分困难。本文通过综述GALNS突变类型和频率、常见突变位点地理分布、基因型与临床表型关系，旨在为黏多糖贮积症Ⅳ A型的早期诊治提供参考。

关键词: 黏多糖贮积症Ⅳ A型, N-乙酰半乳糖胺-6-硫酸酯酶, 基因突变, 基因型, 临床表型

中图分类号:

R725.9

张进, 冉红, 曾宪海, 张鹏, 邱书奇. 黏多糖贮积症Ⅳ A型患者GALNS基因突变的研究进展[J]. 癌变·畸变·突变, 2022, 34(4): 314-317.

参考文献

[1] KHAN S, ALMÉCIGA-DÍAZ C J, SAWAMOTO K, et al.Mucopolysaccharidosis IVA and glycosaminoglycans[J].Mol Genet Metab, 2017, 120(1/2):78-95.
[2] PERACHA H, SAWAMOTO K, AVERILL L, et al.Molecular genetics and metabolism, special edition:diagnosis, diagnosis and prognosis of Mucopolysaccharidosis IVA[J].Mol Genet Metab, 2018, 125(1/2):18-37.
[3] OLARTE-AVELLANEDA S, RODRÍGUEZ-LÓPEZ A, ALMÉCIGADÍAZ C J, et al.Computational analysis of human Nacetylgalactosamine-6-sulfate sulfatase enzyme:an update in genotype-phenotype correlation for Morquio A[J].Mol Biol Rep, 2014, 41(11):7073-7088.
[4] TOMATSU S, OKAMURA K, MAEDA H, et al.Keratan sulphate levels in mucopolysaccharidoses and mucolipidoses[J].J Inherit Metab Dis, 2005, 28(2):187-202.
[5] LIN H Y, LEE C L, CHANG C Y, et al.Survival and diagnostic age of 175 Taiwanese patients with mucopolysaccharidoses (1985-2019)[J].Orphanet J Rare Dis, 2020, 15(1):314.
[6] GALIMBERTI C, MADEO A, DI ROCCO M, et al.Mucopolysaccharidoses:early diagnostic signs in infants and children[J].Ital J Pediatr, 2018, 44(Sup 2):133.
[7] COSMA M P, PEPE S, ANNUNZIATA I, et al.The multiple sulfatase deficiency gene encodes an essential and limiting factor for the activity of sulfatases[J].Cell, 2003, 113(4):445-456.
[8] TOMATSU S, YASUDA E, PATEL P, et al.Morquio A syndrome:diagnosis and current and future therapies[J].Pediatr Endocrinol Rev, 2014, 12 Sup 1(1):141-151.
[9] SAWAMOTO K, GONZÁLEZ J V Á, PIECHNIK M, et al.Mucopolysaccharidosis IVA:diagnosis, treatment, and management[J].Int J Mol Sci, 2020, 21(4):1517.
[10] 中华医学会儿科学分会内分泌遗传代谢学组,中国医师协会医学遗传医师分会临床生化遗传专业委员会,中国医师协会青春期医学专业委员会临床遗传学组.黏多糖贮积症ⅣA型诊治共识[J].中华儿科杂志, 2021, 59(5):361-367.
[11] GLÖSSL J, TRUPPE W, KRESSE H.Purification and properties of N-acetylgalactosamine 6-sulphate sulphatase from human placenta[J].Biochem J, 1979, 181(1):37-46.
[12] TOMATSU S, FUKUDA S, MASUE M, et al.Morquio disease:isolation, characterization and expression of full-length cDNA for human N-acetylgalactosamine-6-sulfate sulfatase[J].Biochem Biophys Res Commun, 1991, 181(2):677-683.
[13] HENDRIKSZ C J, HARMATZ P, BECK M, et al.Review of clinical presentation and diagnosis of mucopolysaccharidosis IVA[J].Mol Genet Metab, 2013, 110(1/2):54-64.
[14] SUKEGAWA K, NAKAMURA H, KATO Z, et al.Biochemical and structural analysis of missense mutations in Nacetylgalactosamine-6-sulfate sulfatase causing mucopolysaccharidosis IVA phenotypes[J].Hum Mol Genet, 2000, 9(9):1283-1290.
[15] RIVERA-COLÓN Y, SCHUTSKY E K, KITA A Z, et al.The structure of human GALNS reveals the molecular basis for mucopolysaccharidosis IV A[J].J Mol Biol, 2012, 423(5):736-751.
[16] PSHEZHETSKY A V, ASHMARINA M.Lysosomal multienzyme complex:biochemistry, genetics, and molecular pathophysiology[J].2001, 69:81-114.
[17] 郑文彬,胡静,赵笛辰,等.罕见黏多糖贮积症ⅣA型致病基因GALNS突变谱和骨骼表型[J].中华骨质疏松和骨矿盐疾病杂志, 2021, 14(2):114-125.
[18] MORRONE A, CACIOTTI A, ATWOOD R, et al.Morquio A syndrome-associated mutations:a review of alterations in the GALNS gene and a new locus-specific database[J].Hum Mutat, 2014, 35(11):1271-1279.
[19] ZANETTI A, D'AVANZO F, ALSAYED M, et al.Molecular basis of mucopolysaccharidosis IVA (Morquio A syndrome):a review and classification of GALNS gene variants and reporting of 68 novel variants[J].Hum Mutat, 2021, 42(11):1384-1398.
[20] LEADLEY R M, LANG S, MISSO K, et al.A systematic review of the prevalence of Morquio A syndrome:challenges for study reporting in rare diseases[J].Orphanet J Rare Dis, 2014, 9:173.
[21] LEONG H Y, ABDUL AZIZE N A, CHEW H B, et al.Clinical, biochemical and genetic profiles of patients with mucopolysaccharidosis type IVA (Morquio A syndrome) in Malaysia:the first national natural history cohort study[J].Orphanet J Rare Dis, 2019, 14(1):1-10.
[22] LIN H Y, CHUANG C K, CHEN M R, et al.Natural history and clinical assessment of Taiwanese patients with mucopolysaccharidosis IVA[J].Orphanet J Rare Dis, 2014, 9:21.
[23] KHEDHIRI S, CHKIOUA L, ELCIOGLU N, et al.Mutations and polymorphisms in N-acetylgalactosamine-6-sulfate sulfatase gene in Turkish Morquio A patients[J].Pathol Biol, 2014, 62(1):38-40.
[24] TAPIERO-RODRIGUEZ S M, ACOSTA GUIO J C, PORRASHURTADO G L, et al.Determination of genotypic and clinical characteristics of Colombian patients with mucopoly-saccharidosis IVA[J].Appl Clin Genet, 2018, 11:45-57.
[25] BOCHERNITSAN A N, BRUSIUS-FACCHIN A C, COUTO R R, et al.Spectrum of GALNS mutations and haplotype study in Brazilian patients with mucopolysaccharidosis type IVA[J].Meta Gene, 2018, 16:77-84.
[26] MOISAN L, IANNUZZI D, MARANDA B, et al.Clinical characteristics of patients from Quebec, Canada, with Morquio A syndrome:a longitudinal observational study[J].Orphanet J Rare Dis, 2020, 15(1):270.
[27] BIDCHOL A M, DALAL A, SHAH H, et al.GALNS mutations in Indian patients with mucopolysaccharidosis IVA[J].Am J Med Genet A, 2014, 164A (11):2793-2801.
[28] 王成礼,阴怀清,石岩,等.1例黏多糖病ⅣA型儿童GALNS基因突变分析[J].中国当代医药, 2013, 20(15):9-10, 13.
[29] GENTILI C, CANCEDDA R.Cartilage and bone extracellular matrix[J].Curr Pharm Des, 2009, 15(12):1334-1348.
[30] JEZELA-STANEK A, RÓŻDŻYŃSKA-ŚWIĄTKOWSKA A, KULPANOVICH A, et al.Novel data on growth phenotype and causative genotypes in 29 patients with Morquio (Morquio-Brailsford) syndrome from Central-Eastern Europe[J].J Appl Genetics, 2019, 60(2):163-174.
[31] ALLISTON T.Chondroitin sulfate and growth factor signaling in the skeleton:possible links to MPS VI[J].J Pediatr Rehabil Med, 2010, 3(2):129-138.
[32] MONTAÑO A M, TOMATSU S, GOTTESMAN G S, et al.International Morquio A Registry:clinical manifestation and natural course of Morquio A disease[J].J Inherit Metab Dis, 2007, 30(2):165-174.
[33] TOMATSU S, AVERILL L W, SAWAMOTO K, et al.Obstructive airway in Morquio A syndrome, the past, the present and the future[J].Mol Genet Metab, 2016, 117(2):150-156.