Novel sequence variants of the alpha-galactosidase A gene in patients with Fabry disease.
We carried out molecular studies of 15 unrelated Hungarian families diagnosed with Fabry disease (FD). Genetic analysis of the alpha-galactosidase A gene was performed in 22 hemizygous males and 34 females. One of the female patients with severe disease phenotype showed homozygosity for the recurrent c.644A>G mutation due to parental consanguinity. The c.644A>G mutation that has previously been found mostly in patients with the cardiac variant of FD, was associated with renal but not cardiac involvement in this female and in two other family members. In nine families, eight novel sequence variants such as small deletions (c.363delT, c.477delT, c.746delAC) and single nucleotide changes (c.107T>C, c.493G>C, c.796G>T, c.866T>G, c.871G>A) were found in addition to six previously described private mutations. This report contributes to the identification of novel disease-causing mutations in FD, and increases our knowledge on demographics and molecular characteristics of this rare lysosomal storage disorder. This is the first comprehensive overview of molecular genetic features of Hungarian patients with FD.
Erdos
Melinda
M
Lysosomal Storage Disease Center, Department of Infectious and Pediatric Immunology, Medical and Health Science Center, University of Debrecen, Nagyerdei krt. 98, Debrecen, Hungary.
Németh
Krisztina
K
Tóth
Beáta
B
Constantin
Tamás
T
Rákóczi
Eva
E
Ponyi
Andrea
A
Dajnoki
Angéla
A
Grubits
János
J
Pintér
István
I
Garzuly
Ferencz
F
Hahn
Katalin
K
Bencsik
Krisztina
K
Vécsei
László
L
Fekete
György
G
Maródi
László
L
D000293:Adolescent; D000328:Adult; D001483:Base Sequence; D000795:Fabry Disease / Q000201:enzymology* / Q000235:genetics; D005190:Family; D005260:Female; D014644:Genetic Variation; D006801:Humans; D006814:Hungary; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation; D012150:Polymorphism, Restriction Fragment Length; D000519:alpha-Galactosidase / Q000235:genetics* / Q000378:metabolism
D000519:alpha-Galactosidase