Mutations in the homeodomain of HOXD13 cause syndactyly type 1-c in two Chinese families.
Mutations in the homeodomain of HOXD13 cause syndactyly type 1-c in two Chinese families.
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HOXD13 同源域突变导致两个中国家族 1-c 型并指
DOI：
10.1371/journal.pone.0096192
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Bai Y
中科院分区：
文献类型：
--
作者：
Dai L;Liu D;Song M;Xu X;Xiong G;Yang K;Zhang K;Meng H;Guo H;Bai Y
并指畸形1型（SD 1）是一种常染色体显性肢体畸形，其典型特征是第三和第四手指和/或第二和第三脚趾之间的完全或部分蹼。它的四种亚型（a，B，c和d）是根据可变的表型定义的，但负责的基因尚未确定。SD 1-a定位于染色体3p21.31，SD 1-B定位于2 q34-q36。SD 1-c和SD 1-d非常罕见，据我们所知，尚未鉴定出基因位点。在两个中国家庭与SD 1-c，连锁和单倍型分析定位的疾病位点2 q31 - 2 q32。拷贝数变异（CNV）分析，使用基于阵列的比较基因组杂交（阵列CGH），排除了微缺失或微重复的可能性。对该区域的相关并指基因的序列分析确定了A家族HOXD 13同源结构域中的c.917G>A（p.R306Q）。对家系B的分析鉴定了突变c.916 C>G（p.R306 G），因此证实了遗传同质性。荧光素酶分析表明，这两个突变影响HOXD 13的转录激活能力。HOXD 13突变谱提示不同类型HOXD 13并指畸形之间存在密切的基因型-表型相关性。在携带HOXD 13突变的家族之间和家族内发现了各种表型的重叠。HOXD 13同源结构域中的突变（p.R306Q和p.R306G）导致SD 1-c。SD 1-c与并指畸形有一定的相关性。由于HOXD 13突变的不同类别导致的不同肢体畸形应被视为一个连续的表型，并指畸形的进一步分类应基于表型和基因型。
Syndactyly type 1 (SD1) is an autosomal dominant limb malformation characterized in its classical form by complete or partial webbing between the third and fourth fingers and/or the second and third toes. Its four subtypes (a, b, c, and d) are defined based on variable phenotypes, but the responsible gene is yet to be identified. SD1-a has been mapped to chromosome 3p21.31 and SD1-b to 2q34–q36. SD1-c and SD1-d are very rare and, to our knowledge, no gene loci have been identified. In two Chinese families with SD1-c, linkage and haplotype analyses mapped the disease locus to 2q31-2q32. Copy number variation (CNV) analysis, using array-based comparative genomic hybridization (array CGH), excluded the possibility of microdeletion or microduplication. Sequence analyses of related syndactyly genes in this region identified c.917G>A (p.R306Q) in the homeodomain of HOXD13 in family A. Analysis on family B identified the mutation c.916C>G (p.R306G) and therefore confirmed the genetic homogeneity. Luciferase assays indicated that these two mutations affected the transcriptional activation ability of HOXD13. The spectrum of HOXD13 mutations suggested a close genotype-phenotype correlation between the different types of HOXD13-Syndactyly. Overlaps of the various phenotypes were found both among and within families carrying the HOXD13 mutation. Mutations (p.R306Q and p.R306G) in the homeodomain of HOXD13 cause SD1-c. There are affinities between SD1-c and synpolydactyly. Different limb malformations due to distinct classes of HOXD13 mutations should be considered as a continuum of phenotypes and further classification of syndactyly should be done based on phenotype and genotype.
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影响因子：
3.5
作者：
通讯作者：
--
影响因子：
3.5
作者：
Fantini, Sebastian;Vaccari, Giulia;Zappavigna, Vincenzo
通讯作者：
Zappavigna, Vincenzo
影响因子：
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作者：
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通讯作者：
Latos-Bieleńska A
影响因子：
2
作者：
Garcia-Barcelo, Maria-Mercè;Wong, Kenneth Kak-yuen;Tam, Paul Kwong-hang
通讯作者：
Tam, Paul Kwong-hang
影响因子：
4
作者：
Debeer, P;Bacchelli, C;Goodman, FR
通讯作者：
Goodman, FR