Department of Neurology, Renmin Hospital of Wuhan University, Wuhan, 430060, China.
Department of Neurology, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, Zhengzhou, 450003, China.
Orphanet J Rare Dis. 2023 Jan 5;18(1):2. doi: 10.1186/s13023-022-02612-2.
Iron-refractory iron deficiency anaemia (IRIDA) is an autosomal recessive iron deficiency anaemia caused by mutations in the TMPRSS6 gene. Iron deficiency anaemia is common, whereas IRIDA is rare. The prevalence of IRIDA is unclear. This study aimed to estimate the carrier frequency and genetic prevalence of IRIDA using Genome Aggregation Database (gnomAD) data.
The pathogenicity of TMPRSS6 variants was interpreted according to the American College of Medical Genetics and Genomics (ACMG) and the Association for Molecular Pathology (AMP) standards and guidelines. The minor allele frequency (MAF) of TMPRSS6 gene disease-causing variants in 141,456 unique individuals was examined to estimate the global prevalence of IRIDA in seven ethnicities: African/African American (afr), American Admixed/Latino (amr), Ashkenazi Jewish (asj), East Asian (eas), Finnish (fin), Non-Finnish European (nfe) and South Asian (sas). The global and population-specific carrier frequencies and genetic prevalence of IRIDA were calculated using the Hardy-Weinberg equation.
In total, 86 pathogenic/likely pathogenic variants (PV/LPV) were identified according to ACMG/AMP guideline. The global carrier frequency and genetic prevalence of IRIDA were 2.02 per thousand and 1.02 per million, respectively.
The prevalence of IRIDA is greater than previous estimates.
铁难治性缺铁性贫血（IRIDA）是一种常染色体隐性遗传性缺铁性贫血，由 TMPRSS6 基因突变引起。缺铁性贫血很常见，而 IRIDA 则很少见。IRIDA 的患病率尚不清楚。本研究旨在利用基因组聚集数据库（gnomAD）数据估算 IRIDA 的携带者频率和遗传患病率。
根据美国医学遗传学与基因组学学院（ACMG）和分子病理学协会（AMP）的标准和指南来解释 TMPRSS6 变异的致病性。检查了 141456 个独特个体中 TMPRSS6 基因致病变异的次要等位基因频率（MAF），以估算七种族裔的 IRIDA 全球患病率：非洲/非裔美国人（afr）、美洲混合/拉丁裔（amr）、阿什肯纳兹犹太人（asj）、东亚人（eas）、芬兰人（fin）、非芬兰欧洲人（nfe）和南亚人（sas）。使用哈迪-温伯格方程计算 IRIDA 的全球和人群特异性携带者频率和遗传患病率。
根据 ACMG/AMP 指南，共鉴定出 86 种致病性/可能致病性变异（PV/LPV）。IRIDA 的全球携带者频率和遗传患病率分别为 2.02/每千人和 1.02/每百万人。
IRIDA 的患病率高于之前的估计。
