IDUA Mutational Profiling of a Cohort of 102 European Patients with Mucopolysaccharidosis Type I: Identification and Characterization of 35 Novel α-L-iduronidase (IDUA) Alleles

被引：61

作者：

Bertola, Francesca ^{[1
]}

Filocamo, Mirella ^{[2
]}

Casati, Giorgio ^{[1
]}

Mort, Matthew ^{[3
]}

Rosano, Camillo ^{[4
]}

Tylki-Szymanska, Anna ^{[5
]}

Tuysuz, Beyhan ^{[6
]}

Gabrielli, Orazio ^{[7
]}

Grossi, Serena ^{[2
]}

Scarpa, Maurizio ^{[8
]}

Parenti, Giancarlo ^{[9
,10
]}

Antuzzi, Daniela ^{[11
]}

Dalmau, Jaime ^{[12
]}

Di Rocco, Maja ^{[13
]}

Vici, Carlo Dionisi ^{[14
]}

Okur, Ilyas ^{[15
]}

Rosell, Jordi ^{[16
]}

Rovelli, Attilio ^{[17
]}

Furlan, Francesca ^{[17
]}

Rigoldi, Miriam ^{[17
]}

Biondi, Andrea ^{[17
]}

Cooper, David N. ^{[3
]}

Parini, Rossella ^{[17
]}

机构：

[1] Milano Bicocca Univ, Consortium Human Mol Genet, I-20052 Monza, Italy

[2] IRCCS G Gaslini, SSD Lab Diag Prepostnatale Malattie Metab, Genoa, Italy

[3] Cardiff Univ, Inst Med Genet, Sch Med, Cardiff CF14 4XN, S Glam, Wales

[4] Ist Nazl Ric Canc, I-16132 Genoa, Italy

[5] Childrens Mem Hlth Inst, Dept Metab Dis, Warsaw, Poland

[6] Istanbul Univ, Div Genet, Dept Pediat, Cerrahpasa Fac Med, Istanbul, Turkey

[7] Polytech Univ Marche, Osped Riuniti, Div Pediat, Ancona, Italy

[8] Univ Padua, Dept Pediat, Univ Childrens Hosp, I-35100 Padua, Italy

[9] Telethon Inst Genet & Med, Naples, Italy

[10] Univ Naples Federico II, Dept Pediat, Naples, Italy

[11] Catholic Univ, Dept Pediat Sci, Rome, Italy

[12] Hosp Infantil La Fe, Div Metab, Valencia, Spain

[13] IRCCS G Gaslini, SS Malattie Rare, UO Pediat 2, Genoa, Italy

[14] Bambino Gesu Pediat Hosp, Div Metab, Rome, Italy

[15] Gazi Univ, Dept Pediat Nutr & Metab, Sch Med, Ankara, Turkey

[16] Hosp Univ Son Dureta, Dept Genet, Palma de Mallorca, Spain

[17] Univ Milano Bicocca, Dept Pediat, San Gerardo Hosp, Monza, Italy

来源：

HUMAN MUTATION | 2011年 / 32卷 / 06期

关键词：

IDUA; mucoplysaccharidosis type I; Hurler disease; genotype-phenotype analysis; molecular modelling; MutPred analysis; in vitro splicing analysis; AMINO-ACID SUBSTITUTIONS; MOLECULAR-GENETICS; MISSENSE MUTATIONS; HUMAN-DISEASE; NOMENCLATURE; EXPRESSION; FREQUENCY; FAMILIES; HURLER; MODEL;

D O I：

10.1002/humu.21479

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

Mutational analysis of the IDUA gene was performed in a cohort of 102 European patients with mucopolysaccharidosis type I. A total of 54 distinct mutant IDUA alleles were identified, 34 of which were novel including 12 missense mutations, 2 nonsense mutations, 12 splicing mutations, 5 micro-deletions, 1 micro-duplication 1 translational initiation site mutation, and 1 'no-stop' change (p.X654RextX62). Evidence for the pathological significance of all novel mutations identified was sought by means of a range of methodological approaches, including the assessment of evolutionary conservation, RT-PCR/in vitro splicing analysis, MutPred analysis and visual inspection of the 3D-model of the IDUA protein. Taken together, these data not only demonstrate the remarkable mutational heterogeneity characterizing type 1 mucopolysaccharidosis but also illustrate our increasing ability to make deductions pertaining to the genotype-phenotype relationship in disorders manifesting a high degree of allelic heterogeneity. (C) 2011 Wiley-Liss, Inc.

引用

页码：E2189 / E2210

页数：22

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