Abstract
Hunter syndrome (Mucopolysaccharidosis type II) is a rare X-linked recessive lysosomal storage disorder caused by the deficiency of the enzyme iduronate-2-sulfatase (IDS). To date, more than 200 different mutations have been reported in the IDS gene, located on Xq27.3-q28. Here, we report two new mutations (M488I and G489A) identified in hemizygosity in an Italian Hunter patient. Their "in vitro" expression by COS 7 cells was carried out in order to evaluate their functional consequence on enzyme activity as well as their possible cumulative effect on the malfunctioning of the protein. The results obtained enabled us to confirm the G489A mutation as causative. The M488I mutation, however, could not be unequivocally considered as causing disease because of its residual activity. Although a cumulative effect of the two mutations can be excluded "in vitro," we are cautious about drawing a conclusion with regard to the possible role that the two mutations could have played "in vivo" in modulating the phenotype of the patient. Finally, the knowledge of the molecular defect of the patient has enabled us to identify the carriers, providing reliable genetic counselling to the females of the family.
| Original language | English |
|---|---|
| Pages (from-to) | 84-87 |
| Number of pages | 4 |
| Journal | American Journal of Medical Genetics |
| Volume | 120 A |
| Issue number | 1 |
| Publication status | Published - Jul 1 2003 |
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Keywords
- COS cells
- Hunter syndrome
- Iduronate-2-sulfatase
- Mucopolysaccharidosis type II
- Transient expression
ASJC Scopus subject areas
- Genetics(clinical)
Cite this
Expression studies of two novel in CIS-mutations identified in an intermediate case of Hunter syndrome. / Ricci, Verena; Filocamo, Mirella; Regis, Stefano; Corsolini, Fabio; Stroppiano, Marina; Di Duca, Marco; Gatti, Rosanna.
In: American Journal of Medical Genetics, Vol. 120 A, No. 1, 01.07.2003, p. 84-87.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Expression studies of two novel in CIS-mutations identified in an intermediate case of Hunter syndrome
AU - Ricci, Verena
AU - Filocamo, Mirella
AU - Regis, Stefano
AU - Corsolini, Fabio
AU - Stroppiano, Marina
AU - Di Duca, Marco
AU - Gatti, Rosanna
PY - 2003/7/1
Y1 - 2003/7/1
N2 - Hunter syndrome (Mucopolysaccharidosis type II) is a rare X-linked recessive lysosomal storage disorder caused by the deficiency of the enzyme iduronate-2-sulfatase (IDS). To date, more than 200 different mutations have been reported in the IDS gene, located on Xq27.3-q28. Here, we report two new mutations (M488I and G489A) identified in hemizygosity in an Italian Hunter patient. Their "in vitro" expression by COS 7 cells was carried out in order to evaluate their functional consequence on enzyme activity as well as their possible cumulative effect on the malfunctioning of the protein. The results obtained enabled us to confirm the G489A mutation as causative. The M488I mutation, however, could not be unequivocally considered as causing disease because of its residual activity. Although a cumulative effect of the two mutations can be excluded "in vitro," we are cautious about drawing a conclusion with regard to the possible role that the two mutations could have played "in vivo" in modulating the phenotype of the patient. Finally, the knowledge of the molecular defect of the patient has enabled us to identify the carriers, providing reliable genetic counselling to the females of the family.
AB - Hunter syndrome (Mucopolysaccharidosis type II) is a rare X-linked recessive lysosomal storage disorder caused by the deficiency of the enzyme iduronate-2-sulfatase (IDS). To date, more than 200 different mutations have been reported in the IDS gene, located on Xq27.3-q28. Here, we report two new mutations (M488I and G489A) identified in hemizygosity in an Italian Hunter patient. Their "in vitro" expression by COS 7 cells was carried out in order to evaluate their functional consequence on enzyme activity as well as their possible cumulative effect on the malfunctioning of the protein. The results obtained enabled us to confirm the G489A mutation as causative. The M488I mutation, however, could not be unequivocally considered as causing disease because of its residual activity. Although a cumulative effect of the two mutations can be excluded "in vitro," we are cautious about drawing a conclusion with regard to the possible role that the two mutations could have played "in vivo" in modulating the phenotype of the patient. Finally, the knowledge of the molecular defect of the patient has enabled us to identify the carriers, providing reliable genetic counselling to the females of the family.
KW - COS cells
KW - Hunter syndrome
KW - Iduronate-2-sulfatase
KW - Mucopolysaccharidosis type II
KW - Transient expression
UR - http://www.scopus.com/inward/record.url?scp=0041821844&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0041821844&partnerID=8YFLogxK
M3 - Article
C2 - 12794697
AN - SCOPUS:0041821844
VL - 120 A
SP - 84
EP - 87
JO - American Journal of Medical Genetics, Part A
JF - American Journal of Medical Genetics, Part A
SN - 1552-4825
IS - 1
ER -