Mutations of the GLA gene in Korean patients with Fabry disease and frequency of the E66Q allele as a functional variant in Korean newborns

Lee, Beom Hee; Heo, Sun Hee; Kim, Gu Hwan; Park, Jung Young; Kim, Woo Shik; Kang, Duk Hee; Choe, Kyung Hoon; Kim, Won Ho; Yang, Song; Yoo, Han Wook

doi:10.1038/jhg.2010.58

Cited by 48 publications

(39 citation statements)

References 34 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…It should be addressed that previous studies included subjects with the p.E66Q allele as a 'renal variant' of Fabry disease. 14,15,17,26 However, Lee et al 22 reported that the allele A g ea te n r o l l m e n t( y e a r ) 5 5 6 1 4 5 8 3 7 6 7 0 7 6 6 7 7 6 8 0 frequency of p.E66Q in Korean individuals was remarkably higher (1.046% (95% confidence interval, 0.458-1.634%)) than the prevalence of Fabry disease. They also demonstrated that p.E66Q was a functional polymorphism rather than a pathogenic mutation using COS-7 cells overexpressing a-GLA harboring p.E66Q.…”

Section: Discussionmentioning

confidence: 97%

See 1 more Smart Citation

High-throughput screening identified disease-causing mutants and functional variants of α-galactosidase A gene in Japanese male hemodialysis patients

et al. 2012

View full text Add to dashboard Cite

Section: Discussionmentioning

confidence: 97%

“…4,17,21 The others (Cases 3-10) had a p.E66Q allele that had been reported previously as a functional polymorphism (rs28935191). 22 Notably, serum GLA activity of these p.E66Q patients were higher than the p.G195V and p.M296I patients ( Figure 5). …”

Section: Fabry Disease Screening In Dialysis Patientsmentioning

confidence: 99%

High-throughput screening identified disease-causing mutants and functional variants of α-galactosidase A gene in Japanese male hemodialysis patients

et al. 2012

View full text Add to dashboard Cite

“…Class 1 mutations have a high probability of causing disease. Class 2 mutations are nonpathogenic polymorphisms and include five missense changes (p.E66Q, p.S102L, p.S126G, p.D313Y, p.F396Y) (23,27). Therefore, the two patients in this study with detectable lyso-Gb3 levels and the p.E66Q mutation (cases 2 and 3 in Table 1) have not begun ERT.…”

Section: Discussionmentioning

confidence: 99%

“…Seven had a missense mutation in GLA (c.196G.C, p.E66Q) ( Table 2) that occurs at an unexpectedly high frequency in Japanese and Korean patients screened for FD. It is not a pathogenic mutation, but a functional polymorphism (23,24).…”

Section: Verification Of Lyso-gb3 Accuracymentioning

confidence: 99%

Screening of Male Dialysis Patients for Fabry Disease by Plasma Globotriaosylsphingosine

Maruyama

Takata²,

Tsubata

et al. 2013

Clinical Journal of the American Society of Nephrology

View full text Add to dashboard Cite

Summary Background and objectives Previous reports of Fabry disease screening in dialysis patients indicate that α-galactosidase A activity alone cannot specifically and reliably identify appropriate candidates for genetic testing; a marker for secondary screening is required. Elevated plasma globotriaosylsphingosine is reported to be a hallmark of classic Fabry disease. The purpose of this study was to examine the usefulness of globotriaosylsphingosine as a secondary screening target for Fabry disease. Design, setting, participants, & measurements This study screened 1453 patients, comprising 50% of the male dialysis patients in Niigata Prefecture between July 1, 2010 and July 31, 2011. Screening for Fabry disease was performed by measuring the plasma α-galactosidase A enzyme activity and the globotriaosylsphingosine concentration, by high-performance liquid chromatography. Genetic testing and genetic counseling were provided. Results A low level of plasma α-galactosidase A activity (≤4.0 nmol/h per milliliter) was observed in 47 patients (3.2%). Of these, 3 (0.2%) had detectable globotriaosylsphingosine levels. These patients all had α-galactosidase A gene mutations: one was p.Y173X and two were the nonpathogenic p.E66Q. The patient with p.Y173X started enzyme replacement therapy. Subsequent screening of his family identified the same mutation in his elder sister and her children. Genetic testing for 33 of the other 44 patients detected 7 patients with p.E66Q. Thus, the plasma lyso-Gb3 screen identified Fabry disease with high sensitivity (100%) and specificity (94.3%). Conclusions Plasma globotriaosylsphingosine is a promising secondary screening target that was effective for selecting candidates for genetic counseling and testing and for uncovering unrecognized Fabry disease cases.

show abstract

“…Therefore, it is difficult to determine a direct relationship between the p.E66Q mutation and the pulvinar lesion. The activity of α-Gal A in the patients with the p.E66Q mutation has been previously reported to be lower than that in the patients with the wildtype allele (6,8,11,12). However, the histopathological changes in Fabry disease have yet not been observed in patients with the p.E66Q mutation (9).…”

Section: Discussionmentioning

confidence: 84%

A Patient with the <i>GLA</i> p.E66Q Mutation Exhibiting Vascular Parkinsonism and Bilateral Pulvinar Lesions

et al. 2015

View full text Add to dashboard Cite

A 76-year-old man was admitted to our hospital due to gait difficulty. Brain imaging indicated bilateral pulvinar lesions and moderate white matter lesions. The serum α-galactosidase A levels were measured for the differential diagnosis of bilateral pulvinar lesions and were found to be abnormally low. Therefore, the patient was suspected to have variant Fabry disease. A GLA mutation analysis showed the p.E66Q mutation, which is speculated to be a functional polymorphism rather than a disease-causing mutation of Fabry disease. Enzyme replacement therapy did not result in a marked improvement, however, the disease progression stopped.

show abstract

Mutations of the GLA gene in Korean patients with Fabry disease and frequency of the E66Q allele as a functional variant in Korean newborns

Cited by 48 publications

References 34 publications

High-throughput screening identified disease-causing mutants and functional variants of α-galactosidase A gene in Japanese male hemodialysis patients

High-throughput screening identified disease-causing mutants and functional variants of α-galactosidase A gene in Japanese male hemodialysis patients

Screening of Male Dialysis Patients for Fabry Disease by Plasma Globotriaosylsphingosine

A Patient with the <i>GLA</i> p.E66Q Mutation Exhibiting Vascular Parkinsonism and Bilateral Pulvinar Lesions

Contact Info

Product

Resources

About