A splice donor site mutation in HOXD13 underlies synpolydactyly with cortical bone thinning.
Synpolydactyly 1(SPD1) is a dominantly inherited distal limb anomaly that is characterized by incomplete digit separation and increased number of digits. SPD1 is most commonly caused by polyalanine repeat expansions and mutations in the homeodomain of the HOXD13. We report a splice donor site mutation in HOXD13 associated in most cases with cortical bone thinning. In vitro study of transcripts and truncated protein analysis indicated that c.781+1G>A mutation results in truncated HOXD13 protein p.G190fsX4. Luciferase assay indicated that the truncated HOXD13 protein failed to bind to DNA. The mechanism for this phenotype was truncated protein loss of function.
The Research Center for Medical Genomics, Key Laboratory of Cell Biology, Ministry of Public Health and Key Laboratory of Medical Cell Biology, Ministry of Education, China Medical University, Shenyang 110001, China.
Xiuyan
X
Shi
Chunyan
C
Ji
Lihua
L
Cao
Yuhong
Y
Wu
Yuyang
Y
Shang
Wei
W
Wang
Yang
Y
Luo
D000818:Animals; D001483:Base Sequence; D001857:Bone Matrix / Q000002:abnormalities; D018389:Codon, Nonsense; D004252:DNA Mutational Analysis; D056726:Genetic Association Studies; D018398:Homeodomain Proteins / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D051379:Mice; D041681:NIH 3T3 Cells; D010375:Pedigree; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D022821:RNA Splice Sites; D036141:Receptor, EphA7 / Q000235:genetics; D013576:Syndactyly / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D014158:Transcription, Genetic
D018389:Codon, Nonsense; C513184:HOXD13 protein, human; D018398:Homeodomain Proteins; D022821:RNA Splice Sites; D014157:Transcription Factors; D036141:Receptor, EphA7
HOX; HOXD13; Homeodomain; Limb malformation; Mut F; Mut R; Mutational screening; OMIM; Online Mendelian Inheritance in Man; PVDF; RT-PCR; SDS; SPD; Syndactyly; homeobox gene D13; homeobox-containing; mutation forward; mutation reverse; polyvinylidene difluoride; reverse transcription-polymerase chain reaction; sodium dodecyl sulfate; synpolydactyly