Mutations in DYNC2H1, the cytoplasmic dynein 2, heavy chain 1 motor protein gene, cause short-rib polydactyly type I, Saldino-Noonan type.
Mutations in DYNC2H1, the cytoplasmic dynein 2, heavy chain 1 motor protein gene, cause short-rib polydactyly type I, Saldino-Noonan type.
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DOI：
10.1111/cge.12947
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发表时间：
2017-08
影响因子：
3.5
通讯作者：
Krakow D
中科院分区：
文献类型：
--
作者：
Badiner N;Taylor SP;Forlenza K;Lachman RS;University of Washington Center for Mendelian Genomics;Bamshad M;Nickerson D;Cohn DH;Krakow D
短肋多指综合征（SRPS）是常染色体隐性遗传，遗传异质性的骨骼肌纤毛病。SRPS表型历史上被划分为I - iv型，其中I型最早由Saldino和Noonan在1972年描述。所有形式的SRP的特征性表现包括短水平肋骨，短四肢和多指畸形。SRP I型表型的特征是非常小的胸腔，极端的小肺，非常短的，矿化不良的长骨，多器官系统异常。迄今为止，这种最严重类型的SRP（也称为Saldino-Noonan综合征）的分子基础尚未确定。我们确定了三个符合SRP i型原始表型描述的SRP病例。在所有三个病例中，外显子组序列分析显示DYNC2H1突变的复合杂合性，该突变编码逆行IFT A马达的主要成分，细胞质动力蛋白2重链1。因此，也由DYNC2H1突变引起的SRP I、II、III型和窒息性胸营养不良（ATD）。在这里，我们描述了表型特征，影像学表现，和分子基础的SRP I型。
The short-rib polydactyly syndromes (SRPS) are autosomal recessively inherited, genetically heterogeneous skeletal ciliopathies. SRPS phenotypes were historically categorized as types I–IV, with type I first delineated by Saldino and Noonan in 1972. Characteristic findings among all forms of SRP include short horizontal ribs, short limbs and polydactyly. The SRP type I phenotype is characterized by a very small thorax, extreme micromelia, very short, poorly mineralized long bones, and multiple organ system anomalies. To date, the molecular basis of this most severe type of SRP, also known as Saldino–Noonan syndrome, has not been determined. We identified three SRP cases that fit the original phenotypic description of SRP type I. In all three cases, exome sequence analysis revealed compound heterozygosity for mutations in DYNC2H1, which encodes the main component of the retrograde IFT A motor, cytoplasmic dynein 2 heavy chain 1. Thus SRP type I, II, III and asphyxiating thoracic dystrophy (ATD), which also result from DYNC2H1 mutations. Herein we describe the phenotypic features, radiographic findings, and molecular basis of SRP type I.
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影响因子：
14.8
作者：
Kumar, Prateek;Henikoff, Steven;Ng, Pauline C.
通讯作者：
Ng, Pauline C.
影响因子：
16.6
作者：
Taylor, S. Paige;Dantas, Tiago J.;Duran, Ivan;Wu, Sulin;Lachman, Ralph S.;Nelson, Stanley F.;Cohn, Daniel H.;Vallee, Richard B.;Krakow, Deborah
通讯作者：
Krakow, Deborah
影响因子：
30.8
作者：
Kircher, Martin;Witten, Daniela M.;Jain, Preti;O'Roak, Brian J.;Cooper, Gregory M.;Shendure, Jay
通讯作者：
Shendure, Jay
影响因子：
9.5
作者：
Yourshaw, Michael;Taylor, S. Paige;Nelson, Stanley F.
通讯作者：
Nelson, Stanley F.
影响因子：
4
作者：
BERNSTEIN, R;ISDALE, J;JENKINS, T
通讯作者：
JENKINS, T