Abstract
Alpha-mannosidosis is a recessively inherited disorder due to the deficiency of the lysosomal alpha-mannosidase. We report the molecular analysis performed in two patients with the late onset form of alpha-mannosidosis. Four new alleles were identified: three missense mutations involving highly conserved residues, c.597 C > A (p.H200N), c.1553 T > C (p.L518P) and c.2746 C > A (p.R916S) and a single nucleotide deletion, c.2660delC. In vitro expression studies in COS-1 cells demonstrated that pH200N, p.L518P and p.R916S proteins are expressed but retained no residual enzyme activity. These data are supported by structural 3D analysis which predicted that both p.L518P and p.R916S could affect the interaction of the small E-domain with the active site domain or the main body of the structure while the pH200N might alter substrate binding or other catalytic properties. Finally, the c.2660delC causes a frameshift introducing a premature stop codon (p.T887SfsX45), presuming to be a severe mutation.
| Original language | English |
|---|---|
| Pages (from-to) | 136-139 |
| Number of pages | 4 |
| Journal | Clinica Chimica Acta |
| Volume | 375 |
| Issue number | 1-2 |
| DOIs | |
| Publication status | Published - Jan 2007 |
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Keywords
- 3D structural analysis
- Alpha-d-mannosidase
- Alpha-mannosidosis
- MAN2B1
ASJC Scopus subject areas
- Biochemistry
- Clinical Biochemistry
Cite this
Funtional characterization of four novel MAN2B1 mutations causing juvenile onset alpha-mannosidosis. / Pittis, M. G.; Montalvo, A. L E; Heikinheimo, P.; Sbaragli, M.; Balducci, C.; Persichetti, E.; Van Maldergem, L.; Filocamo, M.; Bembi, B.; Beccari, T.
In: Clinica Chimica Acta, Vol. 375, No. 1-2, 01.2007, p. 136-139.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Funtional characterization of four novel MAN2B1 mutations causing juvenile onset alpha-mannosidosis
AU - Pittis, M. G.
AU - Montalvo, A. L E
AU - Heikinheimo, P.
AU - Sbaragli, M.
AU - Balducci, C.
AU - Persichetti, E.
AU - Van Maldergem, L.
AU - Filocamo, M.
AU - Bembi, B.
AU - Beccari, T.
PY - 2007/1
Y1 - 2007/1
N2 - Alpha-mannosidosis is a recessively inherited disorder due to the deficiency of the lysosomal alpha-mannosidase. We report the molecular analysis performed in two patients with the late onset form of alpha-mannosidosis. Four new alleles were identified: three missense mutations involving highly conserved residues, c.597 C > A (p.H200N), c.1553 T > C (p.L518P) and c.2746 C > A (p.R916S) and a single nucleotide deletion, c.2660delC. In vitro expression studies in COS-1 cells demonstrated that pH200N, p.L518P and p.R916S proteins are expressed but retained no residual enzyme activity. These data are supported by structural 3D analysis which predicted that both p.L518P and p.R916S could affect the interaction of the small E-domain with the active site domain or the main body of the structure while the pH200N might alter substrate binding or other catalytic properties. Finally, the c.2660delC causes a frameshift introducing a premature stop codon (p.T887SfsX45), presuming to be a severe mutation.
AB - Alpha-mannosidosis is a recessively inherited disorder due to the deficiency of the lysosomal alpha-mannosidase. We report the molecular analysis performed in two patients with the late onset form of alpha-mannosidosis. Four new alleles were identified: three missense mutations involving highly conserved residues, c.597 C > A (p.H200N), c.1553 T > C (p.L518P) and c.2746 C > A (p.R916S) and a single nucleotide deletion, c.2660delC. In vitro expression studies in COS-1 cells demonstrated that pH200N, p.L518P and p.R916S proteins are expressed but retained no residual enzyme activity. These data are supported by structural 3D analysis which predicted that both p.L518P and p.R916S could affect the interaction of the small E-domain with the active site domain or the main body of the structure while the pH200N might alter substrate binding or other catalytic properties. Finally, the c.2660delC causes a frameshift introducing a premature stop codon (p.T887SfsX45), presuming to be a severe mutation.
KW - 3D structural analysis
KW - Alpha-d-mannosidase
KW - Alpha-mannosidosis
KW - MAN2B1
UR - http://www.scopus.com/inward/record.url?scp=33751017084&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=33751017084&partnerID=8YFLogxK
U2 - 10.1016/j.cca.2006.06.034
DO - 10.1016/j.cca.2006.06.034
M3 - Article
C2 - 16919251
AN - SCOPUS:33751017084
VL - 375
SP - 136
EP - 139
JO - Clinica Chimica Acta
JF - Clinica Chimica Acta
SN - 0009-8981
IS - 1-2
ER -