Mutations in two regions of FLNB result in atelosteogenesis I and III
Mutations in two regions of FLNB result in atelosteogenesis I and III
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DOI：
10.1002/humu.20348
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发表时间：
2006-07-01
期刊：
影响因子：
3.9
通讯作者：
Krakow, Deborah
中科院分区：
文献类型：
--
作者：
Farrington-Rock, Claire;Firestein, Marc H.;Krakow, Deborah
微丝蛋白是一个细胞质蛋白家族，其结合并组织肌动蛋白丝，将膜蛋白连接到细胞骨架，并为信号分子提供支架。编码细丝蛋白B（FLNB）的基因突变可引起一系列骨软骨发育不良，包括I型骨发育不全（AOI）和III型骨发育不全（AOIII）。AOI和AOIII是常染色体显性遗传致死性骨骼发育不良，其特征在于重叠的临床表现，包括椎骨异常、骨骼成熟不协调、长骨发育不良和关节脱位。先前的研究表明，改变细丝蛋白B的CH 2结构域和重复6区域的错义突变的杂合性产生AOI和AOIII。在这项研究中，14个新的错义突变FLNB发现在15例无关的AOI和AOIII患者。大多数突变位于外显子2和外显子3，编码肌动蛋白的CH 2结构域，细丝蛋白B的结合区。其余突变位于外显子28和外显子29，编码细丝蛋白B重复序列14和15。这些结果表明，聚集在FLNB的两个区域的突变产生AOI/AOIII，并强调了这种细胞骨架蛋白在正常骨骼发生中的重要作用。参见Mutat 27（7），705- 710，2006。出版日期：2006年Wiley，利斯，Inc.（匕首）。
The filamins are a family of cytoplasmic proteins that bind to and organize actin filaments, link membrane proteins to the cytoskeleton, and provide a scaffold for signaling molecules. Mutations in the gene encoding filamin B (FLNB) cause a spectrum of osteochondrodysplasias, including atelosteogenesis type I (AOI) and atelosteogenesis type III (AOIII). AOI and AOIII are autosomal dominant lethal skeletal dysplasias characterized by overlapping clinical findings that include vertebral abnormalities, disharmonious skeletal maturation, hypoplastic long bones, and joint dislocations. Previous studies have shown that heterozygosity for missense mutations that alter the CH2 domain and repeat 6 region of filamin B produce AOI and AOIII. In this study, 14 novel missense mutations in FLNB were found in 15 unrelated patients with AOI and AOIII. The majority of the mutations resided in exon 2 and exon 3, which encode the CH2 domain of the actin,binding region of filamin B. The remaining mutations were found in exon 28 and exon 29, which encode repeats 14 and 15 of filamin B. These results show that clustering of mutations in two regions of FLNB produce AOI/AOIII, and highlight the important role of this cytoskeletal protein in normal skeletogenesis. Hum Mutat 27(7), 705-710,2006. Published 2006 Wiley,Liss, Inc.(dagger).