TY - JOUR
T1 - Two novel alpha-galactosidase A mutations causing Fabry disease
T2 - A missense mutation M11V in a heterozygote woman and a nonsense mutation R190X in a hemizygote man
AU - Celtikci, Basak
AU - Topçu, Meral
AU - Ozkara, Hatice Asuman
PY - 2011/7/1
Y1 - 2011/7/1
N2 - Objectives: To evaluate the nature of the molecular lesions in the alpha-galactosidase A gene of two patients having Fabry disease. Methods: Enzyme analyses were done using 4-methylumbellyferyl alpha-galactoside as substrate. Single stranded conformational polymorphism analysis and DNA sequencing were performed following PCR amplification of seven exons of alpha-galactosidase A gene. Results: Two new mutations, M11V and R190X, were identified. The female patient with M11V mutation had rheumatologic symptoms, microalbuminuria. The male patient with R190X mutation had a classical phenotype. M11V mutation is in the signal sequence of the peptide and may affect the targeting of the ribosomes to ER. R190X mutation causes premature termination, and probably leads to degradation of the protein. Conclusion: This is the first study in our country investigating the molecular aspects of Fabry disease. It provides the molecular basis for understanding the underlying mechanism of Fabry disease, allows prenatal diagnosis and provides genotype/phenotype correlations.
AB - Objectives: To evaluate the nature of the molecular lesions in the alpha-galactosidase A gene of two patients having Fabry disease. Methods: Enzyme analyses were done using 4-methylumbellyferyl alpha-galactoside as substrate. Single stranded conformational polymorphism analysis and DNA sequencing were performed following PCR amplification of seven exons of alpha-galactosidase A gene. Results: Two new mutations, M11V and R190X, were identified. The female patient with M11V mutation had rheumatologic symptoms, microalbuminuria. The male patient with R190X mutation had a classical phenotype. M11V mutation is in the signal sequence of the peptide and may affect the targeting of the ribosomes to ER. R190X mutation causes premature termination, and probably leads to degradation of the protein. Conclusion: This is the first study in our country investigating the molecular aspects of Fabry disease. It provides the molecular basis for understanding the underlying mechanism of Fabry disease, allows prenatal diagnosis and provides genotype/phenotype correlations.
KW - Alpha-galactosidase A
KW - Fabry disease
KW - Missense mutation
KW - Nonsense mutation
UR - http://www.scopus.com/inward/record.url?scp=79958858126&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=79958858126&partnerID=8YFLogxK
U2 - 10.1016/j.clinbiochem.2011.04.022
DO - 10.1016/j.clinbiochem.2011.04.022
M3 - Article
C2 - 21569769
AN - SCOPUS:79958858126
VL - 44
SP - 809
EP - 812
JO - Clinical Biochemistry
JF - Clinical Biochemistry
SN - 0009-9120
IS - 10-11
ER -