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.
Lysosomal Storage Disease Center, Department of Infectious and Pediatric Immunology, Medical and Health Science Center, University of Debrecen, Nagyerdei krt. 98, Debrecen, Hungary.
Melinda
M
Erdos
Krisztina
K
Németh
Beáta
B
Tóth
Tamás
T
Constantin
Eva
E
Rákóczi
Andrea
A
Ponyi
Angéla
A
Dajnoki
János
J
Grubits
István
I
Pintér
Ferencz
F
Garzuly
Katalin
K
Hahn
Krisztina
K
Bencsik
László
L
Vécsei
György
G
Fekete
László
L
Maródi
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