Abstract |
Split-hand/foot malformation (SHFM) is a congenital limb deformity due to the absence or dysplasia of central rays of the autopod. Six SHFM loci have already been identified. Here we describe a Chinese family with autosomal-dominant SHFM1 that has previously been mapped to 7q21.2-21.3. The two affected family members, mother and son, showed deep median clefts between toes, ectrodactyly and syndactyly; the mother also showed triphalangeal thumbs. Exome sequencing and variant screening of candidate genes in the six loci known to be responsible for SHFM revealed a novel heterozygous mutation, c.558G>T (p.(Gln186His)), in distal-less homeobox 5 (DLX5). As DLX5 encodes a transcription factor capable of transactivating MYC, we also tested whether the mutation could affect DLX5 transcription acitivity. Results from luciferase reporter assay revealed that a mutation in DLX5 compromised its transcriptional activity. This is the first report of a mutation in DLX5 leading to autosomal-dominant SHFM1.
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Authors | Xue Wang, Qian Xin, Lin Li, Jiangxia Li, Changwu Zhang, Rongfang Qiu, Chenmin Qian, Hailing Zhao, Yongchao Liu, Shan Shan, Jie Dang, Xianli Bian, Changshun Shao, Yaoqin Gong, Qiji Liu |
Journal | European journal of human genetics : EJHG
(Eur J Hum Genet)
Vol. 22
Issue 9
Pg. 1105-10
(Sep 2014)
ISSN: 1476-5438 [Electronic] England |
PMID | 24496061
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- DLX5 protein, human
- Homeodomain Proteins
- Transcription Factors
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Topics |
- Adult
- Amino Acid Sequence
- Child
- Exome
- Female
- Foot Deformities, Congenital
(diagnosis, genetics)
- Genes, Dominant
- HEK293 Cells
- Hand Deformities, Congenital
(diagnosis, genetics)
- HeLa Cells
- Hearing Loss, Sensorineural
(diagnosis, genetics)
- Heterozygote
- Homeodomain Proteins
(genetics, metabolism)
- Humans
- Male
- Molecular Sequence Data
- Mutation, Missense
- Pedigree
- Transcription Factors
(genetics, metabolism)
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