当前位置: X-MOL 学术Mol. Genet. Metab. › 论文详情
Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)
Acute hepatic porphyrias: Identification of 46 hydroxymethylbilane synthase, 11 coproporphyrinogen oxidase, and 20 protoporphyrinogen oxidase novel mutations.
Molecular Genetics and Metabolism ( IF 3.7 ) Pub Date : 2018-10-26 , DOI: 10.1016/j.ymgme.2018.10.008
Yonina Loskove 1 , Makiko Yasuda 1 , Brenden Chen 1 , Irina Nazarenko 1 , Neal Cody 1 , Robert J Desnick 1
Affiliation  

The acute hepatic porphyrias (AHPs) are inborn errors of heme biosynthesis, which include three autosomal dominant porphyrias, Acute Intermittent Porphyria (AIP), Hereditary Coproporphyria (HCP), and Variegate Porphyria (VP), and the ultra-rare autosomal recessive porphyria, δ-Aminolevulinic Acid Dehydratase Deficiency Porphyria (ADP). AIP, HCP, VP, and ADP each results from loss-of-function (LOF) mutations in their disease-causing genes: hydroxymethylbilane synthase (HMBS); coproporphyrinogen oxidase (CPOX); protoporphyrinogen oxidase (PPOX), and δ-aminolevulinic acid dehydratase (ALAD), respectively. During the 11-year period from January 1, 2007 through December 31, 2017, the Mount Sinai Porphyrias Diagnostic Laboratory diagnosed 315 unrelated AIP individuals with HMBS mutations, including 46 previously unreported mutations, 29 unrelated HCP individuals with CPOX mutations, including 11 previously unreported mutations, and 54 unrelated VP individuals with PPOX mutations, including 20 previously unreported mutations. Overall, of the 1692 unrelated individuals referred for AHP molecular diagnostic testing, 398 (23.5%) had an AHP mutation. Of the 650 family members of mutation-positive individuals tested for an autosomal dominant AHP, 304 (46.8%) had their respective family mutation. These data expand the molecular genetic heterogeneity of the AHPs and document the usefulness of molecular testing to confirm the positive biochemical findings in symptomatic patients and identify at-risk asymptomatic family members.

中文翻译:

急性肝卟啉症:鉴定出46种羟甲基胆碱合酶,11种原卟啉原氧化酶和20种原卟啉原氧化酶新突变。

急性肝卟啉症(AHP)是血红素生物合成的先天性错误,包括三个常染色体显性卟啉症,急性间歇性卟啉症(AIP),遗传性卟啉菌(HCP)和变异白斑卟啉症(VP),以及超罕见的常染色体隐性卟啉症, δ-氨基乙酰丙酸脱水酶缺乏症卟啉症(ADP)。AIP,HCP,VP和ADP各自是由其致病基因中的功能丧失(LOF)突变引起的:羟甲基胆碱合酶(HMBS);共原卟啉原氧化酶(CPOX); 原卟啉原氧化酶(PPOX)和δ-氨基乙酰丙酸脱水酶(ALAD)。在2007年1月1日至2017年12月31日这11年中,西奈山卟啉病诊断实验室诊断出315名不相关的AIP个体患有HMBS突变,其中包括46例以前未报告的突变,具有CPOX突变的29个无关HCP个体,包括11个以前未报告的突变,具有PPOX突变的54个无关的VP个人,包括20个先前未报告的突变。总体而言,在接受AHP分子诊断测试的1692位无关个体中,有398位(23.5%)具有AHP突变。在对650例突变阳性个体的家庭成员进行了常染色体显性AHP测试的患者中,有304个(46.8%)有其各自的家族突变。这些数据扩大了AHP的分子遗传异质性,并证明了分子检测的有用性,以证实有症状患者中阳性的生化发现并确定有风险的无症状家庭成员。包括20个以前未报告的突变。总体而言,在接受AHP分子诊断测试的1692位无关个体中,有398位(23.5%)具有AHP突变。在对650例突变阳性个体的家庭成员进行了常染色体显性AHP测试的患者中,有304个(46.8%)有其各自的家族突变。这些数据扩大了AHP的分子遗传异质性,并证明了分子检测的有用性,以证实有症状患者中阳性的生化发现并确定有风险的无症状家庭成员。包括20个以前未报告的突变。总体而言,在接受AHP分子诊断测试的1692位无关个体中,有398位(23.5%)具有AHP突变。在对650例突变阳性个体的家庭成员进行了常染色体显性AHP测试的患者中,有304个(46.8%)有其各自的家族突变。这些数据扩大了AHP的分子遗传异质性,并证明了分子检测的有用性,以证实有症状患者中阳性的生化发现并确定有风险的无症状家庭成员。
更新日期:2019-11-18
down
wechat
bug