Identification and characterization of 13 new mutations in mucopolysaccharidosis type I patients

Ursula Matte; Gouri Yogalingam; Doug Brooks; Sandra Leistner; Ida Schwartz; Luciane Lima; Denise Y. Norato; Jaime M. Brum; Clare Beesley; Bryan Winchester; Roberto Giugliani; John J. Hopwood

doi:10.1016/S1096-7192(02)00200-7

Identification and characterization of 13 new mutations in mucopolysaccharidosis type I patients

Ursula Matte, Gouri Yogalingam, Doug Brooks, Sandra Leistner, Ida Schwartz, Luciane Lima, Denise Y. Norato, Jaime M. Brum, Clare Beesley, Bryan Winchester, Roberto Giugliani, John J. Hopwood

Hopwood Centre For Neurobiology

Research output: Contribution to journal › Article › peer-review

77 Citations (Scopus)

Abstract

In this study we have investigated a group of 29 Brazilian patients, who had been diagnosed with the lysosomal storage disorder, Mucopolysaccharidosis type I (MPS-I). MPS I is caused by a deficiency in the lysosomal hydrolase, α-L-iduronidase. Ninety percent of the MPS I patients in this study were genotyped and revealed 10 recurrent and thirteen novel IDUA gene mutations. Eight of these new mutations and three common mutations W402X, P533R, and R383H were individually expressed in CHO-K1 cells and analyzed for α-L-iduronidase protein and enzyme activity. A correlation was observed between the MPS I patient clinical phenotype and the associated mutant α-L-iduronidase protein/enzyme activity expressed in CHO-K1 cells. This was the first time that Brazilian MPS I patients had been thoroughly analyzed and highlighted the difficulties of mutation screening and clinical phenotype assessment in populations with high numbers of unique mutations.

Original language	English
Pages (from-to)	37-43
Number of pages	7
Journal	Molecular Genetics and Metabolism
Volume	78
Issue number	1
DOIs	https://doi.org/10.1016/S1096-7192(02)00200-7
Publication status	Published or Issued - 1 Jan 2003

Keywords

Expression studies
Hurler syndrome
Lysosomal storage disorders
Mucopolysaccharidosis type I
Scheie syndrome
α-L-Iduronidase

ASJC Scopus subject areas

Endocrinology, Diabetes and Metabolism
Biochemistry
Molecular Biology
Genetics
Endocrinology

Access to Document

10.1016/S1096-7192(02)00200-7

Cite this

@article{d67287dc538840659250dc28009e2173,

title = "Identification and characterization of 13 new mutations in mucopolysaccharidosis type I patients",

abstract = "In this study we have investigated a group of 29 Brazilian patients, who had been diagnosed with the lysosomal storage disorder, Mucopolysaccharidosis type I (MPS-I). MPS I is caused by a deficiency in the lysosomal hydrolase, α-L-iduronidase. Ninety percent of the MPS I patients in this study were genotyped and revealed 10 recurrent and thirteen novel IDUA gene mutations. Eight of these new mutations and three common mutations W402X, P533R, and R383H were individually expressed in CHO-K1 cells and analyzed for α-L-iduronidase protein and enzyme activity. A correlation was observed between the MPS I patient clinical phenotype and the associated mutant α-L-iduronidase protein/enzyme activity expressed in CHO-K1 cells. This was the first time that Brazilian MPS I patients had been thoroughly analyzed and highlighted the difficulties of mutation screening and clinical phenotype assessment in populations with high numbers of unique mutations.",

keywords = "Expression studies, Hurler syndrome, Lysosomal storage disorders, Mucopolysaccharidosis type I, Scheie syndrome, α-L-Iduronidase",

author = "Ursula Matte and Gouri Yogalingam and Doug Brooks and Sandra Leistner and Ida Schwartz and Luciane Lima and Norato, {Denise Y.} and Brum, {Jaime M.} and Clare Beesley and Bryan Winchester and Roberto Giugliani and Hopwood, {John J.}",

note = "Funding Information: Much of this work was completed at Women{\textquoteright}s and Children{\textquoteright}s Hospital in Adelaide. This work was supported by a Program Grant from the National Health and Medical Council of Australia. UM received a scholarship from CNPq. Funding for this research in Brazil was obtained from PRONEX-MCT and FIPE-HCPA. C.B. and B.W. acknowledge support from The Society For Mucopolysaccharide Diseases, UK.",

year = "2003",

month = jan,

day = "1",

doi = "10.1016/S1096-7192(02)00200-7",

language = "English",

volume = "78",

pages = "37--43",

journal = "Molecular Genetics and Metabolism",

issn = "1096-7192",

publisher = "Academic Press Inc.",

number = "1",

}

TY - JOUR

T1 - Identification and characterization of 13 new mutations in mucopolysaccharidosis type I patients

AU - Matte, Ursula

AU - Yogalingam, Gouri

AU - Brooks, Doug

AU - Leistner, Sandra

AU - Schwartz, Ida

AU - Lima, Luciane

AU - Norato, Denise Y.

AU - Brum, Jaime M.

AU - Beesley, Clare

AU - Winchester, Bryan

AU - Giugliani, Roberto

AU - Hopwood, John J.

N1 - Funding Information: Much of this work was completed at Women’s and Children’s Hospital in Adelaide. This work was supported by a Program Grant from the National Health and Medical Council of Australia. UM received a scholarship from CNPq. Funding for this research in Brazil was obtained from PRONEX-MCT and FIPE-HCPA. C.B. and B.W. acknowledge support from The Society For Mucopolysaccharide Diseases, UK.

PY - 2003/1/1

Y1 - 2003/1/1

N2 - In this study we have investigated a group of 29 Brazilian patients, who had been diagnosed with the lysosomal storage disorder, Mucopolysaccharidosis type I (MPS-I). MPS I is caused by a deficiency in the lysosomal hydrolase, α-L-iduronidase. Ninety percent of the MPS I patients in this study were genotyped and revealed 10 recurrent and thirteen novel IDUA gene mutations. Eight of these new mutations and three common mutations W402X, P533R, and R383H were individually expressed in CHO-K1 cells and analyzed for α-L-iduronidase protein and enzyme activity. A correlation was observed between the MPS I patient clinical phenotype and the associated mutant α-L-iduronidase protein/enzyme activity expressed in CHO-K1 cells. This was the first time that Brazilian MPS I patients had been thoroughly analyzed and highlighted the difficulties of mutation screening and clinical phenotype assessment in populations with high numbers of unique mutations.

AB - In this study we have investigated a group of 29 Brazilian patients, who had been diagnosed with the lysosomal storage disorder, Mucopolysaccharidosis type I (MPS-I). MPS I is caused by a deficiency in the lysosomal hydrolase, α-L-iduronidase. Ninety percent of the MPS I patients in this study were genotyped and revealed 10 recurrent and thirteen novel IDUA gene mutations. Eight of these new mutations and three common mutations W402X, P533R, and R383H were individually expressed in CHO-K1 cells and analyzed for α-L-iduronidase protein and enzyme activity. A correlation was observed between the MPS I patient clinical phenotype and the associated mutant α-L-iduronidase protein/enzyme activity expressed in CHO-K1 cells. This was the first time that Brazilian MPS I patients had been thoroughly analyzed and highlighted the difficulties of mutation screening and clinical phenotype assessment in populations with high numbers of unique mutations.

KW - Expression studies

KW - Hurler syndrome

KW - Lysosomal storage disorders

KW - Mucopolysaccharidosis type I

KW - Scheie syndrome

KW - α-L-Iduronidase

UR - http://www.scopus.com/inward/record.url?scp=0347297299&partnerID=8YFLogxK

U2 - 10.1016/S1096-7192(02)00200-7

DO - 10.1016/S1096-7192(02)00200-7

M3 - Article

C2 - 12559846

AN - SCOPUS:0347297299

SN - 1096-7192

VL - 78

SP - 37

EP - 43

JO - Molecular Genetics and Metabolism

JF - Molecular Genetics and Metabolism

IS - 1

ER -

Identification and characterization of 13 new mutations in mucopolysaccharidosis type I patients

Abstract

Keywords

ASJC Scopus subject areas

Access to Document

Other files and links

Cite this