Exome sequencing reveals a heterozygous DLX5 mutation in a Chinese family with autosomal-dominant split-hand/foot malformation.
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.
Key Laboratory for Experimental Teratology of the Ministry of Education, Department of Medical Genetics, Shandong University School of Medicine, Jinan, China.
Xue
X
Wang
Key Laboratory for Experimental Teratology of the Ministry of Education, Department of Medical Genetics, Shandong University School of Medicine, Jinan, China.
Qian
Q
Xin
Department of Medical Genetics, Linyi People's Hospital, Linyi, China.
Lin
L
Li
Key Laboratory for Experimental Teratology of the Ministry of Education, Department of Medical Genetics, Shandong University School of Medicine, Jinan, China.
Jiangxia
J
Li
Department of Orthopedics, Cangshan People's Hospital, Cangshan, China.
Changwu
C
Zhang
Key Laboratory for Experimental Teratology of the Ministry of Education, Department of Medical Genetics, Shandong University School of Medicine, Jinan, China.
Rongfang
R
Qiu
Department of Biochemistry, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China.
Chenmin
C
Qian
Key Laboratory for Experimental Teratology of the Ministry of Education, Department of Medical Genetics, Shandong University School of Medicine, Jinan, China.
Hailing
H
Zhao
Key Laboratory for Experimental Teratology of the Ministry of Education, Department of Medical Genetics, Shandong University School of Medicine, Jinan, China.
Yongchao
Y
Liu
Key Laboratory for Experimental Teratology of the Ministry of Education, Department of Medical Genetics, Shandong University School of Medicine, Jinan, China.
Shan
S
Shan
Key Laboratory for Experimental Teratology of the Ministry of Education, Department of Medical Genetics, Shandong University School of Medicine, Jinan, China.
Jie
J
Dang
Key Laboratory for Experimental Teratology of the Ministry of Education, Department of Medical Genetics, Shandong University School of Medicine, Jinan, China.
Xianli
X
Bian
Key Laboratory for Experimental Teratology of the Ministry of Education, Department of Medical Genetics, Shandong University School of Medicine, Jinan, China.
Changshun
C
Shao
Key Laboratory for Experimental Teratology of the Ministry of Education, Department of Medical Genetics, Shandong University School of Medicine, Jinan, China.
Yaoqin
Y
Gong
Key Laboratory for Experimental Teratology of the Ministry of Education, Department of Medical Genetics, Shandong University School of Medicine, Jinan, China.
Qiji
Q
Liu
D000328:Adult; D000595:Amino Acid Sequence; D002648:Child; D059472:Exome; D005260:Female; D005532:Foot Deformities, Congenital / Q000175:diagnosis / Q000235:genetics*; D005799:Genes, Dominant; D057809:HEK293 Cells; D006228:Hand Deformities, Congenital / Q000175:diagnosis / Q000235:genetics*; D006367:HeLa Cells; D006319:Hearing Loss, Sensorineural / Q000175:diagnosis / Q000235:genetics*; D006579:Heterozygote; D018398:Homeodomain Proteins / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D020125:Mutation, Missense; D010375:Pedigree; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism
C100596:DLX5 protein, human; D018398:Homeodomain Proteins; D014157:Transcription Factors