Exome sequencing reveals a heterozygous DLX5 mutation in a Chinese family with autosomal-dominant split-hand/foot malformation.

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.

• 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)

Chemical References

• DLX5 protein, human
• Homeodomain Proteins
• Transcription Factors

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)