title: Genotype: A Crucial but Not Unique Factor Affecting the Clinical Phenotypes in Fabry Disease.
abstract: Numerous α-galactosidase A (α-gal A) gene (GLA) mutations have been identified in Fabry disease (FD), but studies on genotype-phenotype correlation are limited. This study evaluated the features of GLA gene mutations and genotype-phenotype relationship in Chinese FD patients. Gene sequencing results, demographic information, clinical history, and laboratory findings were collected from 73 Chinese FD patients. Totally 47 mutations were identified, including 23 novel mutations which might be pathogenic. For male patients, those with frameshift and nonsense mutations presented the classical FD, whereas those with missense mutations presented both of classical and atypical phenotypes. Interestingly, two male patients with missense mutation p.R356G from two unrelated families, and two with p.R301Q from one family presented different phenotypes. A statistically significant association was found between the levels of α-gal A enzyme activity and ocular changes in males, though no significant association was found between residual enzyme activity level and genotype or clinical phenotypes. For female patients, six out of seven with frameshift mutations and one out of nine with missense mutation presented the classical FD, and α-gal A activity in those patients was found to be significantly lower than that of patients with atypical phenotypes (13.73 vs. 46.32 nmol/ml/h/mg). Our findings suggest that the α-gal A activity might be associated with the clinical severity in female patients with FD. But no obvious associations between activity level of α-gal A and genotype or clinical phenotypes were found for male patients.
authors: The department of Nephrology, Ruijin Hospital, the Medical School affiliated to Shanghai Jiaotong University, Shanghai, China.
authors: Xiaoxia
authors: X
authors: Pan
authors: The department of Nephrology, Ruijin Hospital, the Medical School affiliated to Shanghai Jiaotong University, Shanghai, China.
authors: Yan
authors: Y
authors: Ouyang
authors: The department of Nephrology, Ruijin Hospital, the Medical School affiliated to Shanghai Jiaotong University, Shanghai, China.
authors: Zhaohui
authors: Z
authors: Wang
authors: The department of Nephrology, Ruijin Hospital, the Medical School affiliated to Shanghai Jiaotong University, Shanghai, China.
authors: Hong
authors: H
authors: Ren
authors: The department of Nephrology, Ruijin Hospital, the Medical School affiliated to Shanghai Jiaotong University, Shanghai, China.
authors: Pingyan
authors: P
authors: Shen
authors: The department of Nephrology, Ruijin Hospital, the Medical School affiliated to Shanghai Jiaotong University, Shanghai, China.
authors: Weiming
authors: W
authors: Wang
authors: The department of Nephrology, Ruijin Hospital, the Medical School affiliated to Shanghai Jiaotong University, Shanghai, China.
authors: Yaowen
authors: Y
authors: Xu
authors: The department of Nephrology, Ruijin Hospital, the Medical School affiliated to Shanghai Jiaotong University, Shanghai, China.
authors: Liyan
authors: L
authors: Ni
authors: The department of Nephrology, Ruijin Hospital, the Medical School affiliated to Shanghai Jiaotong University, Shanghai, China.
authors: Xialian
authors: X
authors: Yu
authors: The department of Nephrology, Ruijin Hospital, the Medical School affiliated to Shanghai Jiaotong University, Shanghai, China.
authors: Xiaonong
authors: X
authors: Chen
authors: The department of Nephrology, Ruijin Hospital, the Medical School affiliated to Shanghai Jiaotong University, Shanghai, China.
authors: Wen
authors: W
authors: Zhang
authors: The department of Nephrology, Ruijin Hospital, the Medical School affiliated to Shanghai Jiaotong University, Shanghai, China.
authors: Li
authors: L
authors: Yang
authors: The department of Nephrology, Ruijin Hospital, the Medical School affiliated to Shanghai Jiaotong University, Shanghai, China.
authors: Xiao
authors: X
authors: Li
authors: The department of Nephrology, Ruijin Hospital, the Medical School affiliated to Shanghai Jiaotong University, Shanghai, China.
authors: Jing
authors: J
authors: Xu
authors: The department of Nephrology, Ruijin Hospital, the Medical School affiliated to Shanghai Jiaotong University, Shanghai, China.
authors: Nan
authors: N
authors: Chen
mesh_terms: D000328:Adult; D044466:Asian People / Q000235:genetics; D002681:China; D018389:Codon, Nonsense; D000795:Fabry Disease / Q000175:diagnosis* / Q000235:genetics*; D005260:Female; D016368:Frameshift Mutation; D056726:Genetic Association Studies; D005838:Genotype; D006801:Humans; D008297:Male; D009154:Mutation; D020125:Mutation, Missense; D010641:Phenotype; D017422:Sequence Analysis, DNA; D055815:Young Adult; D000519:alpha-Galactosidase / Q000378:metabolism
chemical_list: D018389:Codon, Nonsense; D000519:alpha-Galactosidase