Novel GLA gene mutations in two Chinese families with classic Fabry disease.
OBJECTIVE
To search mutations in GLA gene in two Chinese families with classic Fabry disease.


METHODS
Two families with Fabry disease confirmed by pathological and clinical studies were reported here. In pedigree 1, 12 family members had paroxysmal pain on limb extremities. In pedigree 2, there were 8 patients and most of them had multi-organ involvement at the end stage of the disease. Two probands from the two families together with several of their family members were searched for mutations in GLA gene. After extraction of genomic DNA from peripheral leukocytes, all of the 7 exons and their flanking introns were amplified by PCR and directly sequenced.


RESULTS
Both the proband 1 and proband 2 were identified to be hemizygotes of novel GLA missense mutations. G132T (TGG-->TGT) mutation in exon 1, resulting in the substitution of amino acid from tryptophan to cysteine (W44C), was detected in proband 1. G874C (GCT-->CCT) mutation in exon 6, resulting in the substitution of amino acid from alanine to praline (A292P), was detected in proband 2. Mothers of the 2 probands were heterozygotes carrying the same mutation as their sons.


CONCLUSIONS
We report here 2 novel missense mutations in two Chinese families with classic Fabry disease. Different mutations in the same gene can result in phenotypes with significant deviation. Several female patients with the same clinical manifestations as male patients in the 2 families suggest that the X-linked dominant inheritance of the disease, possibly related to be the random X chromosome inactivation.
Wang
Zhao-xia
ZX
Department of Neurology, Peking University First Hospital, Beijing, PR China.
Zhang
Ying
Y
Bu
Ding-fang
DF
Zhang
Wei
W
Yuan
Yun
Y
D000293:Adolescent; D044466:Asian People; D001483:Base Sequence; D004252:DNA Mutational Analysis; D005091:Exons / Q000235:genetics; D000795:Fabry Disease / Q000235:genetics*; D005192:Family Health; D005260:Female; D006579:Heterozygote; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D020125:Mutation, Missense; D010375:Pedigree; D016133:Polymerase Chain Reaction; D000519:alpha-Galactosidase / Q000235:genetics*
D000519:alpha-Galactosidase