Tomatsu Shunji, Dieter Tatiana, Schwartz Ida V, Sarmient Piedad, Giugliani Roberto, Barrera Luis A, Guelbert Norberto, Kremer Raquel, Repetto Gabriela M, Gutierrez Monica A, Nishioka Tatsuo, Serrato Olga Peña, Montaño Adriana Maria, Yamaguchi Seiji, Noguchi Akihiko
Department of Pediatrics, Pediatric Research Institute, Saint Louis University, 3662 Park Ave., St Louis, MO, 63110-2586, USA.
Medical Genetics Service, Hospital de Clinicas de Porto Alegre, Porto Alegre, RS, Brazil.
J Hum Genet. 2004;49(9):490-494. doi: 10.1007/s10038-004-0178-8. Epub 2004 Aug 11.
Mucopolysaccharidosis IVA (MPS IVA) is a lysosomal storage disorder caused by the deficiency of N-acetylgalactosamine-6-sulfate sulfatase (GALNS). Mutation screening of the GALNS was performed by genomic PCR and direct sequence analyses in 20 MPS IVA patients from Latin America. In this study, 12 different gene mutations including nine unreported ones were identified in 16 severe and four attenuated patients and accounted for 90.0% of the unrelated mutant alleles. The gene alterations were missense mutations except one insertion. Six recurrent mutations, p.A75G, p.G116S, p.G139S, p.N164T, p.R380S, and p.R386C, accounted for 5.0, 10.0, 5.0, 7.5, 5.0, and 32.5% of the unrelated mutant alleles, respectively. The p.R386C mutation was identified in all Latin American populations studied. Eleven mutations correlated with a severe form, while one mutation, p.R380S, was associated with an attenuated form. MPS IVA patients had an elevation of urine and plasma keratan sulfate (KS) concentrations compared with those of the age-matched control. KS concentrations in severe patients were higher than those in attenuated patients. These data provide evidence for extensive allelic heterogeneity and presence of a common mutation in Latin American patients. Accumulation of mutations with clinical description and KS concentration will lead us to predict clinical severity of the patient more precisely.
IVA型粘多糖贮积症（MPS IVA）是一种由N-乙酰半乳糖胺-6-硫酸酯硫酸酯酶（GALNS）缺乏引起的溶酶体贮积症。对来自拉丁美洲的20例MPS IVA患者进行了GALNS基因的突变筛查，采用基因组PCR和直接测序分析。在本研究中，在16例重症患者和4例轻症患者中鉴定出12种不同的基因突变，包括9种未报道的突变，占无关突变等位基因的90.0%。除1例插入突变外，基因改变均为错义突变。6种复发性突变，p.A75G、p.G116S、p.G139S、p.N164T、p.R380S和p.R386C，分别占无关突变等位基因的5.0%、10.0%、5.0%、7.5%、5.0%和32.5%。在所有研究的拉丁美洲人群中均鉴定出p.R386C突变。11种突变与重症形式相关，而1种突变p.R380S与轻症形式相关。与年龄匹配的对照组相比，MPS IVA患者的尿和血浆硫酸角质素（KS）浓度升高。重症患者的KS浓度高于轻症患者。这些数据为拉丁美洲患者中广泛的等位基因异质性和常见突变的存在提供了证据。积累带有临床描述和KS浓度的突变将使我们能够更准确地预测患者的临床严重程度。
