Clinical and Radiographic Features of the Autosomal Recessive form of Brachyolmia Caused by PAPSS2 Mutations
Clinical and Radiographic Features of the Autosomal Recessive form of Brachyolmia Caused by PAPSS2 Mutations
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DOI：
10.1002/humu.22377
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发表时间：
2013-10-01
期刊：
影响因子：
3.9
通讯作者：
Ikegawa, Shiro
中科院分区：
文献类型：
--
作者：
Iida, Aritoshi;Simsek-Kiper, Pelin Ozlem;Ikegawa, Shiro
短肢畸形是一种异质性骨骼发育不良，其特征为全身性扁平脊椎，无明显长骨异常。根据遗传方式和影像学特征，至少有三种类型的短眼症已被假定。我们最近发现了一种常染色体隐性遗传的短肢症，它是由编码PAPS（3-磷酸腺苷5-磷酸硫酸酯）合酶2的基因PAPSS 2的功能缺失突变引起的。为了了解由PAPSS 2突变引起的短眼症（PAPSS 2-短眼症），我们将我们的PAPSS 2突变分析扩展到来自10个家族的13例患者，并在所有患者中鉴定出纯合或复合杂合突变。发现了9种不同的突变：3种剪接供体位点突变，3种错义突变，以及编码区内的3种插入或缺失突变。体外酶试验表明，错义突变也是功能丧失突变。PAPSS 2-短肢症的表型特征包括身材矮小、智力和面容正常、脊柱畸形和近端指间关节宽。影像学特征包括扁平型椎体，椎体呈矩形，终板不规则，伊利亚宽，股骨近端干骺端改变，包括短股骨颈和横纹，以及短管状骨发育不良。PAPSS 2-短眼症包括短眼症的常规临床概念的表型，Hobaek和Toledo型，并且与异常雄激素代谢相关。(C)2013 Wiley Periodicals，Inc.
Brachyolmia is a heterogeneous skeletal dysplasia characterized by generalized platyspondyly without significant long-bone abnormalities. Based on the mode of inheritance and radiographic features, at least three types of brachyolmia have been postulated. We recently identified an autosomal recessive form of brachyolmia that is caused by loss-of-function mutations of PAPSS2, the gene encoding PAPS (3-phosphoadenosine 5-phosphosulfate) synthase 2. To understand brachyolmia caused by PAPSS2 mutations (PAPSS2-brachyolmia), we extended our PAPSS2 mutation analysis to 13 patients from 10 families and identified homozygous or compound heterozygous mutations in all. Nine different mutations were found: three splice donor-site mutations, three missense mutations, and three insertion or deletion mutations within coding regions. In vitro enzyme assays showed that the missense mutations were also loss-of-function mutations. Phenotypic characteristics of PAPSS2-brachyolmia include short-trunk short stature, normal intelligence and facies, spinal deformity, and broad proximal interphalangeal joints. Radiographic features include platyspondyly with rectangular vertebral bodies and irregular end plates, broad ilia, metaphyseal changes of the proximal femur, including short femoral neck and striation, and dysplasia of the short tubular bones. PAPSS2-brachyolmia includes phenotypes of the conventional clinical concept of brachyolmia, the Hobaek and Toledo types, and is associated with abnormal androgen metabolism. (C) 2013 Wiley Periodicals, Inc.