Prevalence of Fabry disease-causing variants in the UK Biobank.
Prevalence of Fabry disease-causing variants in the UK Biobank.
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DOI：
10.1136/jmg-2022-108523
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发表时间：
2023-04
影响因子：
4
通讯作者：
中科院分区：
文献类型：
--
作者：
法布里病是一种X-连锁溶酶体贮积症，由α-半乳糖苷酶A酶缺乏引起，导致神经酰胺三己糖苷在多个器官部位蓄积，并伴有显著的心血管和肾脏受累。基于临床确定的法布里病全球患病率估计值范围为1/40 000至1/170 000。我们的目的是确定英国生物库中法布里病致病变异的患病率。我们从英国生物银行的200643个个体的外显子组测序数据中寻找GLA基因变异。我们使用ACMG/AMP指南（美国医学遗传学学会/分子病理学协会）对致病性进行分类，并将基线生物标志物数据、医院ICD-10（国际疾病分类第10版）代码、全科医生记录和自我报告的健康数据与无致病性变异的患者进行比较。我们鉴定了81个GLA编码变体。我们根据罕见（<1/10000个体）和先前报告导致法布里病或蛋白质截短变体的基础上确定了8种可能的致病变体。36个人携带其中一种变体。在英国生物样本库中，可能致病的法布里病致病变体的患病率为1/5732（晚发型致病变体）和1/200 643（引起经典法布里病的变体）。法布里病引起的GLA变异在一个有经验的人群样本中比报告的法布里病患病率更普遍。这些绝大多数是与晚发病相关的变异。迟发性法布里病的患病率可能超过目前的估计。
Fabry disease is an X-linked lysosomal storage disorder resulting from deficiency of the alpha-galactosidase A enzyme leading to accumulation of globotriaosylceramide in multiple organ sites with prominent cardiovascular and renal involvement. Global prevalence estimates of Fabry disease based on clinical ascertainment range from 1 in 40 000 to 1 in 170 000. We aimed to determine the prevalence of Fabry disease-causing variants in UK Biobank. We sought GLA gene variants in exome sequencing data from 200 643 individuals from UK Biobank. We used ACMG/AMP guidelines (American College of Medical Genetics/Association for Molecular Pathology) to classify pathogenicity and compared baseline biomarker data, hospital ICD-10 (International Classification of Diseases version-10) codes, general practitioner records and self-reported health data with those without pathogenic variants. We identified 81 GLA coding variants. We identified eight likely pathogenic variants on the basis of being rare (<1/10 000 individuals) and either previously reported to cause Fabry disease, or being protein-truncating variants. Thirty-six individuals carried one of these variants. In the UK Biobank, the prevalence of likely pathogenic Fabry disease-causing variants is 1/5732 for late-onset disease-causing variants and 1/200 643 for variants causing classic Fabry disease. Fabry disease-causing GLA variants are more prevalent in an unselected population sample than the reported prevalence of Fabry disease. These are overwhelmingly variants associated with later onset. It is possible the prevalence of later-onset Fabry disease exceeds current estimates.
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影响因子：
64.8
作者：
Bycroft C;Freeman C;Petkova D;Band G;Elliott LT;Sharp K;Motyer A;Vukcevic D;Delaneau O;O'Connell J;Cortes A;Welsh S;Young A;Effingham M;McVean G;Leslie S;Allen N;Donnelly P;Marchini J
通讯作者：
Marchini J
影响因子：
5
作者：
Fry A;Littlejohns TJ;Sudlow C;Doherty N;Adamska L;Sprosen T;Collins R;Allen NE
通讯作者：
Allen NE
影响因子：
1.9
作者：
Sheng, Bun;Yim, Ka Fai;Chak, Wai Leung
通讯作者：
Chak, Wai Leung
影响因子：
3.8
作者：
Stiles, Ashlee R.;Zhang, Haoyue;Young, Sarah P.
通讯作者：
Young, Sarah P.
影响因子：
5.1
作者：
Burton, Barbara K.;Charrow, Joel;Dizikes, George
通讯作者：
Dizikes, George