PEX1 Mutations in Complementation Group 1 of Zellweger Spectrum Patients Correlate with Severity of Disease
PEX1 Mutations in Complementation Group 1 of Zellweger Spectrum Patients Correlate with Severity of Disease
复制标题
Zellweger 谱系患者互补组 1 中的 PEX1 突变与疾病严重程度相关
作者：
N. Preuss;U. Brosius;M. Biermanns;A. Muntau;E. Conzelmann;J. Gärtner
过氧化物酶体生物发生障碍 (PBD) 是一组具有复杂发育和代谢表型的常染色体隐性遗传疾病，包括 Zellweger 谱系和根茎性点状软骨发育不良。这些疾病是由过氧化物酶体基质蛋白输入缺陷引起的，其特征是多种过氧化物酶体代谢功能的丧失。在人类中，已确定了 12 个互补组，其中互补组 1 占所有 PBD 患者的三分之二以上。编码 ATP 酶 AAA 蛋白家族成员的 PEX1 基因突变是造成该组缺陷的原因，并且已经描述了多种 PEX1 突变等位基因。我们对互补组 1 中一组经过详细记录的 Zellweger 谱系患者的 PEX1 基因突变和相关单倍型进行了表征，这些患者代表了广泛的表型变异。我们将突变类型与生存年龄、临床表现和生化改变进行比较，发现基因型与生存年龄之间存在密切关系。错义突变引起较轻微的疾病，而插入、缺失和无义突变则与严重的临床表型相关。因此，了解PEX1基因突变有助于预测个别病例的病程。
The peroxisome biogenesis disorders (PBD) are a group of autosomal-recessive diseases with complex developmental and metabolic phenotypes, including the Zellweger spectrum and rhizomelic chondrodysplasia punctata. The diseases are caused by defects in peroxisomal matrix protein import and are characterized by the loss of multiple peroxisomal metabolic functions. In humans, 12 complementation groups have been identified, with complementation group 1 accounting for more than two thirds of all PBD patients. Mutations in the PEX1 gene encoding a member of the AAA protein family of ATPases are responsible for the defects in this group, and a variety of PEX1 mutant alleles have been described. We characterized the PEX1 gene mutations and associated haplotypes in a group of thoroughly documented Zellweger spectrum patients in complementation group 1 who represent the broad range of phenotypic variation. We compared the type of mutation with the age of survival, clinical manifestations, and biochemical alterations and found a close relationship between genotype and age of survival. Missense mutations cause a milder form of disease, whereas insertions, deletions, and nonsense mutations are associated with severe clinical phenotypes. Thus, knowing the PEX1 gene mutation is helpful in predicting the course of disease in individual cases.
DOI：
10.1073/pnas.95.15.8630
发表时间：
1998-07-21
影响因子：
11.1
作者：
Geisbrecht, BV;Collins, CS;Gould, SJ
通讯作者：
Gould, SJ
影响因子：
5.1
作者：
MOSER, AB;RASMUSSEN, M;MOSER, HW
通讯作者：
MOSER, HW
过氧化物酶体生物发生障碍第 4 组基因 PXAAA1 编码 PTS1 受体稳定性所需的细胞质 ATP 酶。
DOI：
--
发表时间：
1996
期刊：
The EMBO journal
影响因子：
--
作者：
Yahraus,T;Braverman,N;Dodt,G;Kalish,JE;Morrell,JC;Moser,HW;Valle,D;Gould,SJ
通讯作者：
Gould,SJ