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Is the alpha-galactosidase A variant p.Asp313Tyr (p.D313Y) pathogenic for Fabry disease? A systematic review

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@article{4f72fdfc85ec486f9af26b3fff76ef4a,
title = "Is the alpha-galactosidase A variant p.Asp313Tyr (p.D313Y) pathogenic for Fabry disease?: A systematic review",
abstract = "The identification of pathogenic GLA variants plays a central role in the establishment of a definite Fabry disease (FD) diagnosis. We aimed to review and interpret the published data on the p.Asp313Tyr (p.D313Y) variant pathogenicity and clinical relevance. We performed a systematic review of peer-reviewed publications and case-reports on individuals and populations harbouring the p.Asp313Tyr variant. Overall, 35 studies were included in this review. We collected data regarding the clinical manifestations, alpha-galactosidase A enzyme activity, levels of the biomarkers globotriaosylceramide (Gb3 ) and sphingosine-globotriaosylceramide (lyso-Gb3 ) and histological findings of p.Asp313Tyr carriers. The prevalence of p.Asp313Tyr in populations at risk for FD (kidney, heart, neurologic disorders, or symptomatic populations) was calculated. We found high residual enzyme activity, low frequency of clinical features specific for FD, non-elevated lysoGb3 /Gb3 concentrations and lack of intracellular Gb3 accumulation in biopsies in the p.Asp313Tyr carriers. The prevalence of the variant in populations at risk for FD was comparable to the reported frequency in the general population. A possible higher frequency was only observed in neurologic disorders. p.Asp313Tyr can be classified as neutral or variant of unknown significance. Further investigations will be helpful to clarify a possible association between the variant and manifestations in the brain vessels.",
keywords = "D313Y, Fabry disease, GLA gene, mutation, variant",
author = "Grigoris Effraimidis and Rasmussen, {{\AA}se K} and Henning Bundgaard and S{\o}rensen, {S{\o}ren S} and Ulla Feldt-Rasmussen",
note = "{\textcopyright} 2020 SSIEM.",
year = "2020",
month = sep,
doi = "10.1002/jimd.12240",
language = "English",
volume = "43",
pages = "922--933",
journal = "Journal of Inherited Metabolic Disease",
issn = "0141-8955",
publisher = "Springer Netherlands",
number = "5",

}

RIS

TY - JOUR

T1 - Is the alpha-galactosidase A variant p.Asp313Tyr (p.D313Y) pathogenic for Fabry disease?

T2 - A systematic review

AU - Effraimidis, Grigoris

AU - Rasmussen, Åse K

AU - Bundgaard, Henning

AU - Sørensen, Søren S

AU - Feldt-Rasmussen, Ulla

N1 - © 2020 SSIEM.

PY - 2020/9

Y1 - 2020/9

N2 - The identification of pathogenic GLA variants plays a central role in the establishment of a definite Fabry disease (FD) diagnosis. We aimed to review and interpret the published data on the p.Asp313Tyr (p.D313Y) variant pathogenicity and clinical relevance. We performed a systematic review of peer-reviewed publications and case-reports on individuals and populations harbouring the p.Asp313Tyr variant. Overall, 35 studies were included in this review. We collected data regarding the clinical manifestations, alpha-galactosidase A enzyme activity, levels of the biomarkers globotriaosylceramide (Gb3 ) and sphingosine-globotriaosylceramide (lyso-Gb3 ) and histological findings of p.Asp313Tyr carriers. The prevalence of p.Asp313Tyr in populations at risk for FD (kidney, heart, neurologic disorders, or symptomatic populations) was calculated. We found high residual enzyme activity, low frequency of clinical features specific for FD, non-elevated lysoGb3 /Gb3 concentrations and lack of intracellular Gb3 accumulation in biopsies in the p.Asp313Tyr carriers. The prevalence of the variant in populations at risk for FD was comparable to the reported frequency in the general population. A possible higher frequency was only observed in neurologic disorders. p.Asp313Tyr can be classified as neutral or variant of unknown significance. Further investigations will be helpful to clarify a possible association between the variant and manifestations in the brain vessels.

AB - The identification of pathogenic GLA variants plays a central role in the establishment of a definite Fabry disease (FD) diagnosis. We aimed to review and interpret the published data on the p.Asp313Tyr (p.D313Y) variant pathogenicity and clinical relevance. We performed a systematic review of peer-reviewed publications and case-reports on individuals and populations harbouring the p.Asp313Tyr variant. Overall, 35 studies were included in this review. We collected data regarding the clinical manifestations, alpha-galactosidase A enzyme activity, levels of the biomarkers globotriaosylceramide (Gb3 ) and sphingosine-globotriaosylceramide (lyso-Gb3 ) and histological findings of p.Asp313Tyr carriers. The prevalence of p.Asp313Tyr in populations at risk for FD (kidney, heart, neurologic disorders, or symptomatic populations) was calculated. We found high residual enzyme activity, low frequency of clinical features specific for FD, non-elevated lysoGb3 /Gb3 concentrations and lack of intracellular Gb3 accumulation in biopsies in the p.Asp313Tyr carriers. The prevalence of the variant in populations at risk for FD was comparable to the reported frequency in the general population. A possible higher frequency was only observed in neurologic disorders. p.Asp313Tyr can be classified as neutral or variant of unknown significance. Further investigations will be helpful to clarify a possible association between the variant and manifestations in the brain vessels.

KW - D313Y

KW - Fabry disease

KW - GLA gene

KW - mutation

KW - variant

U2 - 10.1002/jimd.12240

DO - 10.1002/jimd.12240

M3 - Review

C2 - 32246457

VL - 43

SP - 922

EP - 933

JO - Journal of Inherited Metabolic Disease

JF - Journal of Inherited Metabolic Disease

SN - 0141-8955

IS - 5

ER -

ID: 59998002