Division of Hematology, Department of Medicine, University of Utah School of Medicine, Salt Lake City, UT.
UMRs 1149, Centre de Recherche sur l'Inflammation, Institut National de la Santé et de la Recherche Médicale, Université Paris Diderot, Paris, France.
Blood Adv. 2022 Feb 8;6(3):760-766. doi: 10.1182/bloodadvances.2021005484.
The Mendelian inheritance pattern of acute intermittent porphyria, hereditary coproporphyria, and variegate porphyria is autosomal dominant, but the clinical phenotype is heterogeneous. Within the general population, penetrance is low, but among first-degree relatives of a symptomatic proband, penetrance is higher. These observations suggest that genetic factors, in addition to mutation of the specific enzyme of the biosynthetic pathway of heme, contribute to the clinical phenotype. Recent studies by others suggested that the genotype of the transporter protein ABCB6 contribute to the porphyria phenotype. Identifying the molecule(s) that are transported by ABCB6 has been problematic and has led to uncertainty with respect to how or if variants/mutants contribute to phenotypic heterogeneity. Knockout mouse models of Abcb6 have not provided a direction for investigation as homozygous knockout animals do not have a discrete phenotype. To address the proposed link between ABC6 genotype and porphyria phenotype, a large cohort of patients with acute hepatic porphyria and erythropoietic protoporphyria was analyzed. Our studies showed that ABCB6 genotype did not correlate with disease severity. Therefore, genotyping of ABCB6 in patients with acute hepatic porphyria and erythropoietic protoporphyria is not warranted.
急性间歇性血卟啉症、遗传性粪卟啉症和变异性血卟啉症的孟德尔遗传模式为常染色体显性遗传，但临床表型具有异质性。在一般人群中，外显率较低，但在有症状先证者的一级亲属中，外显率较高。这些观察结果表明，遗传因素除了突变血红素生物合成途径的特定酶外，还与临床表型有关。其他研究人员最近的研究表明，转运蛋白 ABCB6 的基因型与卟啉症表型有关。鉴定由 ABCB6 转运的分子一直存在问题，并且对变异/突变如何或是否导致表型异质性存在不确定性。Abcb6 敲除小鼠模型并未提供研究方向，因为纯合敲除动物没有明显的表型。为了解决 ABCB6 基因型与卟啉症表型之间的拟议联系，对一大群急性肝性卟啉症和红细胞生成性原卟啉症患者进行了分析。我们的研究表明，ABCB6 基因型与疾病严重程度无关。因此，急性肝性卟啉症和红细胞生成性原卟啉症患者的 ABCB6 基因分型没有必要。
